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    • [Current status of health services rendered by the Department of Neurology, Yokohama City University-affiliated Hospital--from the viewpoint of a psychiatric emergency core hospital]
      Related Articles

      [Current status of health services rendered by the Department of Neurology, Yokohama City University-affiliated Hospital--from the viewpoint of a psychiatric emergency core hospital]

      Seishin Shinkeigaku Zasshi. 2007;109(10):968-75

      Authors: Odawara T, Sugiyama N, Heian Y

      PMID:Latest neurology publications 18309558 [PubMed - in process ( Latest neurology publications ) ]

    • Vitamin C deficiency in weanling guinea pigs: differential expression of oxidative stress and DNA repair in liver and brain.
      Related Articles

      Vitamin C deficiency in weanling guinea pigs: differential expression of oxidative stress and DNA repair in liver and brain.

      Br J Nutr. 2007 Dec;98(6):1116-9

      Authors: Lykkesfeldt J, Trueba GP, Poulsen HE, Christen S

      Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency caused rapid and significant depletion of ascorbate (P < 0.001), tocopherols (P < 0.001) and glutathione (P < 0.001), and a decrease in superoxide dismutase activity (P = 0.005) in the liver, while protein oxidation was significantly increased (P = 0.011). No changes in lipid oxidation or oxidatively damaged DNA were observed in this tissue. In the brain, the pattern was markedly different. Of the measured antioxidants, only ascorbate was significantly depleted (P < 0.001), but in contrast to the liver, ascorbate oxidation (P = 0.034), lipid oxidation (P < 0.001), DNA oxidation (P = 0.13) and DNA incision repair (P = 0.014) were all increased, while protein oxidation decreased (P = 0.003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may therefore be particularly adverse during the neonatal period.

      PMID:Latest neurology publications 18309548 [PubMed - in process ( Latest neurology publications ) ]

    • Modeling individual-specific human optic nerve head biomechanics. Part I: IOP-induced deformations and influence of geometry.
      Related Articles

      Modeling individual-specific human optic nerve head biomechanics. Part I: IOP-induced deformations and influence of geometry.

      Biomech Model Mechanobiol. 2008 Feb 29;

      Authors: Sigal IA, Flanagan JG, Tertinegg I, Ethier CR

      Glaucoma, the second most common cause of blindness worldwide, is an ocular disease characterized by progressive loss of retinal ganglion cell (RGC) axons. Biomechanical factors are thought to play a central role in RGC loss, but the specific mechanism underlying this disease remains unknown. Our goal was to characterize the biomechanical environment in the optic nerve head (ONH)-the region where RGC damage occurs-in human eyes. Post mortem human eyes were imaged, fixed at either 5 or 50 mmHg pressure and processed histologically to acquire serial sections through the ONH. Three-dimensional models of the ONH region were reconstructed from these sections and embedded in a generic scleral shell to create a model of an entire eye. We used finite element simulations to quantify the effects of an acute change in intraocular pressure from 5 to 50 mmHg on the ONH biomechanical environment. Computed strains varied substantially within the ONH, with the pre-laminar neural tissue and the lamina cribrosa showing the greatest strains. The mode of strain having the largest magnitude was third principal strain (compression), reaching 12-15% in both the lamina cribrosa and the pre-laminar neural tissue. Shear strains were also substantial. The distribution of strains in all ONH tissues was remarkably similar between eyes. Inter-individual variations in ONH geometry (anatomy) have only modest effects on ONH biomechanics, and may not explain inter-individual susceptibility to elevated intraocular pressure. Consistent with previous results using generic ONH models, the displacements of the vitreo-retinal interface and the anterior surface of the lamina cribrosa can differ substantially, suggesting that currently available optical imaging methods do not provide information of the acute deformations within ONH tissues. Predicted strains within ONH tissues are potentially biologically significant and support the hypothesis that biomechanical factors contribute to the initial insult that leads to RGC loss in glaucoma.

      PMID:Latest neurology publications 18309526 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • The efficacy of erythropoietin on acute spinal cord injury. An experimental study on a rat model.
      Related Articles

      The efficacy of erythropoietin on acute spinal cord injury. An experimental study on a rat model.

      Arch Orthop Trauma Surg. 2008 Feb 29;

      Authors: Kontogeorgakos VA, Voulgaris S, Korompilias AV, Vekris M, Polyzoidis KS, Bourantas K, Beris AE

      INTRODUCTION: The accumulated knowledge of erythropoietin (EPO) interaction in neural injury has led to potentially novel therapeutic strategies. Previous experimental studies of recombinant human EPO (rhEPO) administration have shown favorable results after central and peripheral neural injury. In the present study we used the aneurysmal clip model to evaluate the efficacy of two different regimes of rhEPO administration on the functional outcome after severe acute spinal cord injury (ASCI). MATERIALS AND METHODS: Thirty rats were operated on with posterior laminectomy at thoracic 10th vertebra. Spinal cord trauma produced by extradural placement of the aneurysm clip, for 1 min. Animals were divided into three groups; the first group received a low total EPO dose (EPO-L), (2 doses of 1,000 IU each s.c.). The second group was administered the high total EPO dose (EPO-H), (14 doses of 1,000 IU each s.c.), and the third was the Control group, which received normal saline in the same time fashion with EPO-H group. Follow-up was for 6 weeks. Estimation of the functional progress of each rat was calculated using the locomotor rating scale of Basso et al, with a range from 0 to 21. RESULTS: After surgery the animals suffered paraplegia with urinary disturbances. Rats that received EPO demonstrated statistically significant functional improvement compared to the Control group, throughout study interval. On the last follow-up at 6 weeks the EPO-L rats achieved a mean score 17.3 +/- 1.15, the EPO-H 14.7 +/- 1.82, and the control group 8.2 +/- 0.78. Comparison between the two EPO groups reveals superior final outcome of the group treated with lower total dose. CONCLUSION: Our study supports current knowledge, that EPO administration has a positive effect on functional recovery after experimental ASCI. These data reflect the positive impact of EPO on the pathophysiologic cascade of secondary neural damage. However, we observed a dose-related effect on functional recovery. Interestingly, large doses do not seem to favor the neurological recovery as lower doses do.

      PMID:Latest neurology publications 18309506 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Communications of the European neurological society.
      Related Articles

      Communications of the European neurological society.

      J Neurol. 2008 Feb;255(2):314-6

      Authors:

      PMID:Latest neurology publications 18309468 [PubMed - in process ( Latest neurology publications ) ]

    • Serum Brain-derived Neurotrophic Factor is Associated with Reduced Appetite in Healthy Older Adults.
      Related Articles

      Serum Brain-derived Neurotrophic Factor is Associated with Reduced Appetite in Healthy Older Adults.

      J Nutr Health Aging. 2008 Mar;12(3):183-5

      Authors: Stanek K, Gunstad J, Leahey T, Glickman E, Alexander T, Spitznagel MB, Juvancic Heltzel J, Murray L

      Objective: Loss of appetite and body mass are common in older adults and are associated with negative consequences. Research indicates that these processes likely involve increases in serum brain-derived neurotrophic factor (BDNF). Animal and human models demonstrate that BDNF may serve a regulatory function in food intake, but no study has addressed the possibility that BDNF may be involved in appetite reduction and loss of body mass in older adults. Design and Participants: 34 older adults without significant neurological or psychiatric history underwent fasting blood draw and measurement of body composition. Appetite and eating behavior were assessed by questionnaire and related to serum BDNF levels. Results: Partial correlations showed serum BDNF levels were inversely related to appetite (r = -.38, p = .02). No significant correlations emerged between serum BDNF and age, diet, or body composition. Conclusions: The current study extends past work and shows that BDNF is associated with appetite in healthy older adults. Further work is needed to clarify mechanisms for these findings, particularly prospective studies.

      PMID:Latest neurology publications 18309438 [PubMed - in process ( Latest neurology publications ) ]

    • Use of femoral nerve blocks in adolescents undergoing patellar realignment surgery.
      Related Articles

      Use of femoral nerve blocks in adolescents undergoing patellar realignment surgery.

      Am J Orthop. 2008 Jan;37(1):39-43

      Authors: Luhmann SJ, Schootman M, Schoenecker PL, Gordon JE, Schrock C

      The purpose of this study was to analyze the efficacy of femoral nerve blocks (FNBs) in decreasing postoperative narcotic use in adolescents undergoing patellar realignment surgery (PRS). All patients who underwent PRS at 2 children's hospitals between 1998 and 2002 were included in the study. Patients were grouped according to postoperative analgesia: FNB (n = 14), as-needed intravenous morphine (PRN-IV; n = 16), or patient-controlled analgesia using morphine (PCA; n = 13). Total postoperative IV morphine use was statistically significantly different among the 3 groups: 9.0 mg for FNB, 26.43 mg for PRN- IV, and 64.7 mg for PCA. FNB use was effective in significantly decreasing postoperative IV narcotic use.

      PMID:Latest neurology publications 18309383 [PubMed - in process ( Latest neurology publications ) ]

    • Infectomic Analysis of Gene Expression Profiles of Human Brain Microvascular Endothelial Cells Infected with Cryptococcus neoformans.
      Related Articles

      Infectomic Analysis of Gene Expression Profiles of Human Brain Microvascular Endothelial Cells Infected with Cryptococcus neoformans.

      J Biomed Biotechnol. 2008;2008(2):375620

      Authors: Jong A, Wu CH, Zhou W, Chen HM, Huang SH

      In order to dissect the pathogenesis of Cryptococcus neoformans meningoencephalitis, a genomic survey of the changes in gene expression of human brain microvascular endothelial cells infected by C. neoformans was carried out in a time-course study. Principal component analysis (PCA) revealed significant fluctuations in the expression levels of different groups of genes during the pathogen-host interaction. Self-organizing map (SOM) analysis revealed that most genes were up- or downregulated 2 folds or more at least at one time point during the pathogen-host engagement. The microarray data were validated by Western blot analysis of a group of genes, including beta-actin, Bcl-x, CD47, Bax, Bad, and Bcl-2. Hierarchical cluster profile showed that 61 out of 66 listed interferon genes were changed at least at one time point. Similarly, the active responses in expression of MHC genes were detected at all stages of the interaction. Taken together, our infectomic approaches suggest that the host cells significantly change the gene profiles and also actively participate in immunoregulations of the central nervous system (CNS) during C. neoformans infection.

      PMID:Latest neurology publications 18309373 [PubMed - in process ( Latest neurology publications ) ]

    • Hormones of the gut-brain axis as targets for the treatment of upper gastrointestinal disorders.
      Related Articles

      Hormones of the gut-brain axis as targets for the treatment of upper gastrointestinal disorders.

      Nat Rev Drug Discov. 2008 Mar;7(3):241-54

      Authors: Sanger GJ, Lee K

      The concept of the gut forming the centre of an integrated gut-brain-energy axis - modulating appetite, metabolism and digestion - opens up new paradigms for drugs that can tackle multiple symptoms in complex upper gastrointestinal disorders. These include eating disorders, nausea and vomiting, gastroesophageal reflux disease, gastroparesis, dyspepsia and irritable bowel syndrome. The hormones that modulate gastric motility represent targets for gastric prokinetic drugs, and peptides that modify eating behaviours may be targeted to develop drugs that reduce nausea, a currently poorly treated condition. The gut-brain axis may therefore provide a range of therapeutic opportunities that deliver a more holistic treatment of upper gastrointestinal disorders.

      PMID:Latest neurology publications 18309313 [PubMed - in process ( Latest neurology publications ) ]

    • Overexpression, Purification, and Preliminary X-ray Crystallographic Analysis of Human Brain-Type Creatine Kinase.
      Related Articles

      Overexpression, Purification, and Preliminary X-ray Crystallographic Analysis of Human Brain-Type Creatine Kinase.

      J Microbiol Biotechnol. 2008 Feb;18(2):295-8

      Authors: Bong SM, Moon JH, Jang EH, Lee KS, Chi YM

      Creatine kinase (CK; E.C. 2.7.3.2) is an important enzyme that catalyzes the reversible transfer of a phosphoryl group from ATP to creatine in energy homeostasis. The brain-type cytosolic isoform of creatine kinase (BB-CK), which is found mainly in the brain and retina, is a key enzyme in brain energy metabolism, because high-energy phosphates are transfered through the creatine kinase/phosphocreatine shuttle system. The recombinant human BB-CK protein was overexpressed as a soluble form in Escherichia coli and crystallized at 22degreeC using PEG 4000 as a precipitant. Native X-ray diffraction data were collected to 2.2 A resolution using synchrotron radiation. The crystals belonged to the tetragonal space group P43212, with cell parameters of a=b=97.963, c= 164.312 A, and alpha=beta=gamma=90o. The asymmetric unit contained two molecules of CK, giving a crystal volume per protein mass (Vm) of 1.80 A3 Da-1 and a solvent content of 31.6%.

      PMID:Latest neurology publications 18309274 [PubMed - in process ( Latest neurology publications ) ]

    • Relationships between spinal landmarks and skin surface markers.
      Related Articles

      Relationships between spinal landmarks and skin surface markers.

      J Appl Biomech. 2008 Feb;24(1):94-7

      Authors: Engsberg JR, Lenke LG, Bridwell KH, Uhrich ML, Trout CM

      This investigation determined relationships between coronal vertical alignment (CVA) and sagittal vertical alignment (SVA) variables calculated from radiographs and surface markers representing bony landmarks. Biplanar radiographs were taken on 28 subjects (standing) after 2 metallic surface markers were placed on the skin superficial to C7 and S2. The CVA-R and SVA-R were measured on the radiographs. Similar variables were calculated from the surface markers (CVA-P-R, SVA-P-R). Correlation between CVA-R and CVA-P-R was 0.894 (p < 0.000), and between SVA-R and SVA-P-R was 0.946 (p < 0.000). Results lead to three recommendations: (1) obtain surface marker data when radiographs are taken to establish relationships between the two sets of data, (2) take care in providing instructions to the subjects if measures are to be taken at different times, and (3) observe caution in interpreting results when simultaneous x-ray and surface marker data were not recorded.

      PMID:Latest neurology publications 18309189 [PubMed - in process ( Latest neurology publications ) ]

    • Retinal Signs and Stroke. Revisiting the Link Between the Eye and Brain.
      Related Articles

      Retinal Signs and Stroke. Revisiting the Link Between the Eye and Brain.

      Stroke. 2008 Feb 28;

      Authors: Baker ML, Hand PJ, Wang JJ, Wong TY

      BACKGROUND AND PURPOSE: The retinal and cerebral vasculature share similar anatomic, physiological, and embryological characteristics. We reviewed the literature, focusing particularly on recent population-based studies, to examine the relationship between retinal signs and stroke. Summary of Review-Hypertensive retinopathy signs (eg, focal retinal arteriolar narrowing, arterio-venous nicking) were associated with prevalent stroke, incident stroke, and stroke mortality, independent of blood pressure and other cerebrovascular risk factors. Diabetic retinopathy signs (eg, microaneurysms, hard exudates) were similarly associated with incident stroke and stroke mortality. Retinal arteriolar emboli were associated with stroke mortality but not incident stroke. There were fewer studies on the association of other retinal signs such as retinal vein occlusion and age-related macular degeneration with stroke, and the results were less consistent. CONCLUSIONS: Many retinal conditions are associated with stroke, reflecting possible concomitant pathophysiological processes affecting both the eye and the brain. However, the incremental value of a retinal examination for prediction of future stroke risk remains to be determined.

      PMID:Latest neurology publications 18309171 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Changes in Background Blood-Brain Barrier Integrity Between Lacunar and Cortical Ischemic Stroke Subtypes.
      Related Articles

      Changes in Background Blood-Brain Barrier Integrity Between Lacunar and Cortical Ischemic Stroke Subtypes.

      Stroke. 2008 Feb 28;

      Authors: Wardlaw JM, Farrall A, Armitage PA, Carpenter T, Chappell F, Doubal F, Chowdhury D, Cvoro V, Dennis MS

      BACKGROUND AND PURPOSE: Lacunar stroke is associated with endothelial dysfunction and histologically with intrinsic cerebral microvascular disease of unknown cause. Endothelial dysfunction could impair blood-brain barrier integrity. We assessed background blood-brain barrier leakage in patients with lacunar ischemic stroke compared with cortical stroke controls. METHODS: We recruited patients with lacunar or mild cortical ischemic stroke and assessed generalized cerebral blood-brain barrier leak with MRI and intravenous gadolinium at least 1 month after stroke. We used detailed image processing to compare signal change before and for 30 minutes postcontrast throughout gray matter, white matter, and cerebrospinal fluid with summary analyses and general linear modeling. RESULTS: Among 48 patients (29 lacunar, 19 cortical), postcontrast enhancement was significantly higher in cerebrospinal fluid (P=0.04, Mann-Whitney U), and nonsignificantly higher in white matter, in lacunar than in cortical strokes, with no difference in gray matter. General linear modeling confirmed significantly greater postcontrast enhancement in cerebrospinal fluid in lacunar patients than in cortical controls (t=3.37, P<0.0008). CONCLUSIONS: These preliminary data suggest that the blood-brain barrier may be dysfunctional throughout subcortical white matter (white matter drains via interstitial spaces to cerebrospinal fluid) in patients with lacunar stroke. Further studies are required to confirm these findings and determine whether abnormal blood-brain barrier might predate development of lacunar disease. Blood-brain barrier dysfunction may be an important mechanism for brain damage in cerebral microvascular disease.

      PMID:Latest neurology publications 18309161 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • The Role of Aquaporin-4 Polymorphisms in the Development of Brain Edema After Middle Cerebral Artery Occlusion.
      Related Articles

      The Role of Aquaporin-4 Polymorphisms in the Development of Brain Edema After Middle Cerebral Artery Occlusion.

      Stroke. 2008 Feb 28;

      Authors: Kleffner I, Bungeroth M, Schiffbauer H, Schäbitz WR, Ringelstein EB, Kuhlenbäumer G

      BACKGROUND AND PURPOSE: Some patients develop severe brain edema after complete middle cerebral artery occlusion, whereas others do not. Aquaporin-4 (AQP4) is the main water channel in the brain and has been shown to be critical for the development of brain edema after ischemia. We asked whether genetic variation in the AQP4 gene is related to the severity of brain edema after middle cerebral artery occlusion. METHODS: We genotyped 10 single nucleotide polymorphisms distributed across the AQP4 gene in 41 patients with middle cerebral artery occlusion with and without severe brain edema and assessed single marker association as well as the linkage dysequilibrium structure across AQP4. RESULTS: One single nucleotide polymorphism (rs9951307) at the 3' end of AQP4 was associated with severe brain edema (dominant model, P=0.01; OR, 0.10; 95% CI, 0.02 to 0.49 for the protective G-allele). Linkage dysequilibrium across AQP4 was low; no clear haplotype blocks could be identified for the assessment of haplotype association. CONCLUSIONS: This explorative study shows that genetic variation in AQP4 might contribute to brain edema formation after middle cerebral artery occlusion and warrants further investigation.

      PMID:Latest neurology publications 18309154 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Risk Factors and Neurological Consequences of Syncopes Induced by Internal Carotid Artery Angioplasty.
      Related Articles

      Risk Factors and Neurological Consequences of Syncopes Induced by Internal Carotid Artery Angioplasty.

      Stroke. 2008 Feb 28;

      Authors: Martinez-Fernandez E, Boza Garcia F, Gonzalez-Marcos JR, Gil-Peralta A, Gonzalez Garcia A, Mayol Deya A

      BACKGROUND AND PURPOSE: Syncope and carotid sinus reactions (CSR) occur frequently in patients undergoing carotid angioplasty (CA). We investigated risk factors and the neurological consequences of carotid sinus syncope induced by CA. METHODS: We examined 359 consecutive patients. Patients underwent assessment of cerebrovascular reserve before CA and continuous electroencephalographical monitoring during the procedure. We examined the impact of vascular risk factors, cerebral hemodynamics, characteristics of plaque, and procedural modality on the incidence of CSR and syncope. The effect of syncopes on periprocedural complication rates was also investigated. RESULTS: CSR and syncope occurred in 62.7% and 18.0% of the procedures, respectively. The occurrence of CSR during angioplasty was significantly associated with the appearance of syncope. The incidence of syncope was significantly higher in longer plaques located in the carotid bifurcation, in the presence of contralateral carotid stenosis, or when protection devices were used. Although TIA during CA was more common in syncopal patients, stroke or death rates were similar in the 2 groups. CONCLUSIONS: Syncope occurs more frequently in patients with long plaques proximal to the carotid bifurcation, but it does not increase the periprocedural complications rate.

      PMID:Latest neurology publications 18309152 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Endothelium dependent and independent vasodilation of the superficial femoral artery in spinal cord-injured subjects.
      Related Articles

      Endothelium dependent and independent vasodilation of the superficial femoral artery in spinal cord-injured subjects.

      J Appl Physiol. 2008 Feb 28;

      Authors: Thijssen DH, Kooijman M, Groot PC, Bleeker MW, Smits P, Green DJ, Hopman MT

      Extreme inactivity of the legs in spinal cord-injured (SCI) individuals does not result in an impairment of the superficial femoral artery flow-mediated dilation (FMD). To gain insight into the underlying mechanism, the present study examined NO-responsiveness of vascular smooth muscles in controls and SCI subjects. METHODS: In 8 healthy men (34+/-13 years) and 6 SCI subjects (37+/-10 years), superficial femoral artery FMD-response was assessed by echo-Doppler. Subsequently, infusion of incremental dosages of sodium-nitroprusside (SNP) was used to assess NO-responsiveness. Maximal diameter was examined on a second day after 13 min of arterial occlusion in combination with sublingual administration of nitroglycerine. RESULTS: Resting and maximal superficial femoral artery diameter in SCI were smaller than in controls (P<0.001). The FMD-response in controls (4.2+/-0.9%) was lower than in SCI (8.2+/-0.9%, P<0.001), but not after correcting for area-under-the-curve for shear rate (P=0.35). When expressed as relative change from baseline, SCI subjects demonstrate a significantly larger diameter increase compared with controls at each dose SNP. However, when expressed as a relative increase within the range of diameter changes (baseline[0%]-maximal diameter[100%]), both groups demonstrate similar changes in response to SNP. CONCLUSION: Changes in diameter during SNP infusion and FMD-response are larger in SCI compared to controls. When these results are corrected, superficial femoral artery FMD and NO sensitivity in SCI are not different from controls. This illustrates the importance of appropriate data presentation and suggests that, subsequent to structural inward remodelling of conduit arteries as a consequence of extreme physical inactivity, arterial function is normalised. Key words: flow mediated dilation, nitric oxide sensitivity, deconditioning, spinal cord injury, endothelium.

      PMID:Latest neurology publications 18309094 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Transplantation of Embryonic Stem Cells Improves Nerve Repair and Functional Recovery after Severe Sciatic Nerve Axotomy in Rats.
      Related Articles

      Transplantation of Embryonic Stem Cells Improves Nerve Repair and Functional Recovery after Severe Sciatic Nerve Axotomy in Rats.

      Stem Cells. 2008 Feb 28;

      Authors: Cui L, Jiang J, Wei L, Zhou X, Fraser JL, Snider BJ, Yu SP

      Extensive research has focused on transplantation of pluripotent stem cells for the treatment of CNS disorders, the therapeutic potential of stem cell therapy for injured peripheral nerves is largely unknown. We used a rat sciatic nerve transection model to test the ability of implanted embryonic stem (ES) cell-derived neural progenitor cells (ES-NPCs) in promoting repair of a severely injured peripheral nerve. Mouse ES cells were neurally induced in vitro; enhanced expression and/or secretion of growth factors were detected in differentiating ES cells. One hour after removal of a 1-cm segment of the left sciatic nerve, ES-NPCs were implanted into the gap between the nerve stumps with the surrounding epineurium as a natural conduit. The transplantation resulted in substantial axonal re-growth and nerve repair, which were not seen in culture medium controls. One to three months after axotomy, co-immunostaining with the mouse neural cell membrane specific antibody M2/M6 and the Schwann cell marker S100 suggested that transplanted ES-NPCs had survived and differentiated into myelinating cells. Regenerated axons were myelinated and showed a uniform connection between proximal and distal stumps. Nerve stumps had near normal diameter with longitudinally oriented, densely packed Schwann cell-like phenotype. Fluoro-Gold retrogradely labeled neurons were found in the spinal cord (T12-13) and DRG (L4 - L6), suggesting reconnection of axons across the transection. Electrophysiological recordings showed functional activity recovered across the injury gap. These data suggest that transplanted neurally induced ES cells differentiate into myelin-forming cells and provide a potential therapy for severely injured peripheral nerves. ______________________________________________________________________________ L. Cui and J. Jiang contributed equally to this work.

      PMID:Latest neurology publications 18308951 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • The effect of exercise on motor performance tasks used in the neurological assessment of sports related concussion.
      Related Articles

      The effect of exercise on motor performance tasks used in the neurological assessment of sports related concussion.

      Br J Sports Med. 2008 Feb 28;

      Authors: Schneiders AG, Sullivan SJ, McCrory PR, Gray AR, Maruthayanar S, Singh P, Ranhotigamage PS, Van der Salm RA

      Sports-related concussion is assessed using both cognitive and motor performance tasks. There is limited understanding how exercise effects these measures.The purpose of this study was to investigate the effect of moderate-intensity exercise on three selected measures of motor performance. A repeated measures design was used to compare baseline motor performance scores to post-exercise scores with an exercise intervention modelled on the physiological demands of a team sport. Thirty physically active subjects performed timed motor performance tasks; Finger-to-Nose (FTN), Tandem Gait (TG) and Single Leg Stance (SLS). The tasks were administered twice pre-exercise and twice post-exercise. FTN, TG and SLS demonstrated high test-retest reliability (ICC values > 0.8). Fifteen minutes of moderate intensity exercise caused a significant improvement in FTN (p = 0.0004) and TG (p = 0.0009), but not in SLS (p = 0.5068). Improvement in the performance of motor tasks after exercise has implications for the immediate assessment of sports related concussion given that measures of motor performance are utilised in concussion assessment instruments.

      PMID:Latest neurology publications 18308895 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • A pilot study to determine the effect of trunk and hip focused neuromuscular training on hip and knee isokinetic strength.
      Related Articles

      A pilot study to determine the effect of trunk and hip focused neuromuscular training on hip and knee isokinetic strength.

      Br J Sports Med. 2008 Feb 28;

      Authors: Myer G, Brent J, Ford K, Hewett T

      OBJECTIVES: The objective was to determine the effect of trunk focused neuromuscular training (TNMT) on hip and knee strength. The hypothesis was that TNMT would increase standing isokinetic hip abduction, but not knee flexion/extension, strength. <br> METHODS: Twenty-one (TMNT n=14: 15.4 +/- 1.4 yrs, 170.5 +/- 5.0 cm, 64.1 +/- 8.5 kg; CTRL n =7: 16.0 +/- 1.7 yrs, 173.4 +/- 10.0 cm, 63.9 +/- 5.3 kg; p>0.05) high school female volleyball players were recruited to participate in this study. Fourteen participated in TNMT protocol (2 X/wk) over a ten week period in addition to their standard off-season strength training (1X/wk). Standing isokinetic hip abduction strength and seated knee flexion/extension strength were measured prior to and after TNMT.<br> RESULTS: A significant interaction of group and time was observed. The TNMT group increased isokinetic hip abduction strength approximately 15% (13.5% dominant leg: 46.6 +/- 10.1 to 52.9 +/- 11.4 ft-lbs and 17.1% in the non-dominant leg: 46.1 +/- 10.4 to 54.0 +/- 10.7 ft-lbs; p = 0.01). There was no difference in the control group in pre- versus post-test measures. Post-test results also indicated no effect of TNMT on isokinetic knee extension (p=0.57) or knee flexion (p=0.57) strength.<br> CONCLUSIONS: Ten weeks of TNMT increased standing hip abduction strength in female athletes. Increased hip abduction strength and recruitment may improve the ability of female athletes to increase control of lower extremity alignment and decrease loads resulting from increased trunk displacement during sports activities.

      PMID:Latest neurology publications 18308886 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Functional evidence for purinergic inhibitory neuromuscular transmission in the mouse internal anal sphincter.
      Related Articles

      Functional evidence for purinergic inhibitory neuromuscular transmission in the mouse internal anal sphincter.

      Am J Physiol Gastrointest Liver Physiol. 2008 Feb 28;

      Authors: McDonnell BM, Hamilton R, Fong M, Ward SM, Keef KD

      The neurotransmitter(s) underlying NOS-independent neural inhibition in the IAS is still uncertain. The present study investigated the role of purinergic transmission. Contractile and electrical responses to electrical field stimulation of nerves (0.1-5 Hz for 10-60 sec) were recorded in strips of mouse IAS. A single stimulus generated a 28 mV fast inhibitory junction potential (F-IJP) and relaxation. The NOS inhibitor L-NNA reduced the F-IJP duration by 20%. Repetitive stimulation at 2.5-5 Hz caused a more sustained IJP and sustained relaxation. L-NNA reduced relaxation at 1 Hz and the sustained IJP at 2.5-5 Hz. All other experiments were carried out in the presence of NOS blockade. IJPs and relaxation were significantly reduced by the P2 receptor antagonists PPADS (100microM), by desensitization of P2Y receptors with ADPbetaS (10microM) and by the selective P2Y1 receptor blocker MRS2179 (10microM). Relaxation and IJPs were also significantly reduced by the K(+) channel blocker apamin (1microM). Removal of extracellular potassium (Ko) increased IJP amplitude to 205% of control whereas return of Ko 30 minutes later hyperpolarized cells by 19 mV and reduced IJP amplitude to 50% of control. Exogenous ATP (3mM) relaxed muscles in the presence of TTX (1microM) and hyperpolarized cells by 15 mV. In conclusion, these data suggest that purinergic transmission significantly contributes to NOS-independent neural inhibition in the mouse IAS. P2Y1 receptors as well as at least one other P2 receptor subtype contribute to this pathway. Purinergic receptors activate apamin sensitive K(+) channels as well as other apamin-insensitive conductances leading to hyperpolarization and relaxation. Key words: gastrointestinal, enteric nervous system, neuromuscular transmission, smooth muscle, membrane potential.

      PMID:Latest neurology publications 18308858 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Regulation of Progesterone Receptor Expression by Estradiol is dependent on Age, Sex and Region in the Rat Brain.
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      Regulation of Progesterone Receptor Expression by Estradiol is dependent on Age, Sex and Region in the Rat Brain.

      Endocrinology. 2008 Feb 28;

      Authors: Quadros PS, Wagner CK

      Progesterone receptor (PR) expression is highly dependent on estradiol in the medial preoptic nucleus (MPN) and the ventromedial nucleus (VMN) of the adult rat brain. During development, males express high levels of PR in the MPN whereas females have virtually no PR, a sex difference resulting entirely from differential exposure to estradiol. Because PR is also estradiol-dependent in the adult VMN, the present study examined the regulation of PR-immunoreactivity (PRir) in the developing VMN. Surprisingly, PRir was present at high levels in the VMN of both neonatal males and females. In the neonatal VMN, PR expression was dependent on gonadal hormones in males but not in females. When females were ovariectomized and exposed to estradiol at various ages from neonatal to adulthood, estradiol reliably induced PRir in the MPN at P7 but failed to induce PRir in the VMN of the same animals. Only later in development, around P14, did estradiol increase PRir in the female VMN. There appears to be a developmental "switch" in the VMN when PR expression changes from estradiol-independent to estradiol-dependent. Furthermore, this "switch" is anatomically specific and does not exist in the MPN. The present results indicate that the regulation of PR expression by estradiol is dependent on age, sex and brain region, suggesting that PR may play a critical, but specific role in the normal development of these reproductively-important brain areas. In addition, the neonatal female VMN may provide a unique model in which to examine the mechanisms underlying the specificity of steroid-induced gene expression.

      PMID:Latest neurology publications 18308846 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Mini Review: Progestin Receptor Subtypes in the Brain: The known and the Unknown.
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      Mini Review: Progestin Receptor Subtypes in the Brain: The known and the Unknown.

      Endocrinology. 2008 Feb 28;

      Authors: Mani S

      Progesterone (P), the most biologically active "progestin" of ovarian origin, modulates numerous cellular functions in the central nervous system to coordinate physiology and reproduction. The neurobiological activity of P is mediated not by a single form of the progestin receptor (PR), but by two neural isoforms of PRs, PR-A and PR-B. Classical model of P action assumes that these neural effects are primarily mediated via their intracellular PRs, acting as transcriptional regulators, in steroid sensitive neurons, modulating genes and genomic networks. Evidence has emerged, however, that activation of neural PRs is much more diverse: four distinct classes of molecules, neurotransmitters, peptide growth factors, cyclic nucleotides and neurosteroids have been shown to activate the PRs via cross-talk and pathway convergence. In addition, rapid signaling events associated with membrane receptors and/or subpopulations of cytoplasmic PRs, via activation of protein kinase cascades, regulate PR gene expression in the cytoplasm independent of PR nuclear action. The increasing in vitro and in vivo evidence of differential transcriptional activities and co-regulator interactions between PR-A and PR-B, predict that these isoforms could have distinct roles in mediating additional and/or alternate signaling pathways within steroid sensitive neurons. In this minireview, we evaluate the available data and discuss the possible roles of the isoforms in the regulation of neurobiological processes.

      PMID:Latest neurology publications 18308838 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Structural brain correlates of response inhibition in Bipolar Disorder I.
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      Structural brain correlates of response inhibition in Bipolar Disorder I.

      J Psychopharmacol. 2008 Feb 28;

      Authors: Haldane M, Cunningham G, Androutsos C, Frangou S

      Deficits in response inhibition are a prominent feature of Bipolar Disorder, type I (BDI). The purpose of this study was to examine the relationship between inhibitory control and cerebral structure as it may inform our understanding of the pathophysiology of BDI. Inhibitory control was measured in remitted patients with BDI (n _ 44) and healthy controls (n _ 44), using the interference score from the Stroop Colour Word Task and the scaled total error score from the Hayling Sentence Completion Test. Structural magnetic resonance imaging brain scans were also obtained for all participants. For both measures, better performance in controls correlated positively with gray matter volume in the dorsal and ventral prefrontal cortical (PFC) regions with parietal involvement additionally seen for the interference score. In contrast, better inhibitory control in BDI patients correlated positively with gray matter volume in the right parietal cortical regions, namely the cuneus for the scaled total error score and the inferior parietal lobule for the interference score. The observed lack of correlation between PFC grey matter and measures of inhibitory control in BDI patients is suggestive of PFC dysfunction; the correlation between response inhibition and parietal grey matter volume may be indicative of a compensatory involvement of the parietal cortices in BDI.

      PMID:Latest neurology publications 18308812 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Changes in brain orexin levels in a rat model of depression induced by neonatal administration of clomipramine.
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      Changes in brain orexin levels in a rat model of depression induced by neonatal administration of clomipramine.

      J Psychopharmacol. 2008 Feb 28;

      Authors: Feng P, Vurbic D, Wu Z, Hu Y, Strohl KP

      Depression is associated with a deficiency of serotonergic neurons that have been found to suppress orexinergic neurons, which in turn activate these neurons in a feedback loop. This evidence suggests that orexins may be involved in the pathology of depression. Long Evans rats were treated with clomipramine (CLI) and saline (SAL) from postnatal days 8 through 21. One set of rats from both groups was sacrificed at 35 days of age for quantification of orexins in multiple brain regions. At 3-4 months of age a second set of rats was tested for immobility in a forced swim procedure, a common test for depressive signs in rats, and a third set was sacrificed for the quantification of orexins. Compared with the control rats, adult rats with neonatal CLI treatment had (1) increased forced swim immobility and (2) increased orexins A and B in the hypothalamus. However, both orexins A and B levels were decreased in multiple brain regions in the juvenile CLI rats compared with same-age controls. We concluded that although orexin levels were decreased in juvenile CLI rats, adult CLI rats with features of depression had significantly higher levels of hypothalamic orexins compared with adult controls. These results imply that orexins are likely to be involved in the pathological regulation of depression.

      PMID:Latest neurology publications 18308806 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Effects of acute or 3-day treatments of Hypericum caprifoliatum Cham. & Schltdt. (Guttiferae) extract or of two established antidepressants on basal and stress-induced increase in serum and brain corticosterone levels.
      Related Articles

      Effects of acute or 3-day treatments of Hypericum caprifoliatum Cham. & Schltdt. (Guttiferae) extract or of two established antidepressants on basal and stress-induced increase in serum and brain corticosterone levels.

      J Psychopharmacol. 2008 Feb 28;

      Authors: Viana AF, Rates SM, Naudin B, Janin F, Costentin J, do Rego JC

      Since depressive patients present alterations in the hypothalamopituitary- adrenal (HPA) axis that are normalised by antidepressants, this HPA axis has been considered as a target of their actions. We have investigated the mechanism of action of a cyclohexane extract of Hypericum caprifoliatum (HCP), which displays antidepressant like activity, by studying, in mice, the influence of HCP and of two established antidepressant drugs, imipramine and bupropion, administered either acutely or semi-chronically (once a day, three consecutive days), on serum and brain cortex corticosterone levels, either in basal conditions or shortly after a forced-swimming session (FSS). Administered acutely, imipramine (20mg/kg, per os (p.o.)), bupropion (30mg/kg, p.o.) and HCP (360mg/kg, p.o.) significantly reduced the immobility time and had no effects on FSS-induced increase of serum and cortical corticosterone levels. Conversely, 3 days repeated treatment with imipramine or bupropion resulted in a significant reduction of immobility time and FSSinduced increase of serum and cortical corticosterone levels. In a different way, repeated treatment with HCP significantly reduced the immobility time and only cortical corticosterone levels in stressed mice. These results indicate that short-term treatments with antidepressants are sufficient to induce modifications in the HPA axis reactivity to stress; and that apparently HCP has an influence on corticosterone levels by a mechanism diverse from the other tested antidepressants.

      PMID:Latest neurology publications 18308787 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Improvement in cardiac sympathetic nerve activity in responders to resynchronization therapy.
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      Improvement in cardiac sympathetic nerve activity in responders to resynchronization therapy.

      Europace. 2008 Mar;10(3):374-8

      Authors: Burri H, Sunthorn H, Somsen A, Fleury E, Stettler C, Shah D, Righetti A

      Aims To assess changes in cardiac adrenergic activity with cardiac resynchronization therapy (CRT), and to investigate whether these changes are related to improvement in left ventricular ejection fraction (LVEF). Methods and results Sixteen patients (13 males, age 66 +/- 7 years) were studied at baseline and after >/=6 months of CRT (mean follow-up 9.2 +/- 3.2 months). LVEF was assessed by nuclear angiography. Responders were defined as patients showing >/=5% absolute increase in LVEF + improvement in >/=1 NYHA class + absence of heart failure hospitalization. Cardiac sympathetic nerve activity was studied by (123)I-metaiodobenzyl-guanidine ((123)I-MIBG) scintigraphy. Responders (n = 8) showed lower (123)I-MIBG washout at follow-up when compared with non-responders (P = 0.002), indicating lower cardiac sympathetic nerve activity. The decrease in (123)I-MIBG washout at follow-up when compared with baseline was only seen in the responder group (P = 0.036). There was a moderate correlation between increase in LVEF and decrease in (123)I-MIBG washout (r = 0.52, P = 0.04). Conclusion CRT induces a reduction in cardiac sympathetic nerve activity in responders, that parallels an improvement in LVEF, whereas non-responders do not show any significant changes.

      PMID:Latest neurology publications 18308757 [PubMed - in process ( Latest neurology publications ) ]

    • Diabetic neuropathy.
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      Diabetic neuropathy.

      Diabetes Care. 2008 Mar;31(3):616-21

      Authors: Bloomgarden ZT

      PMID:Latest neurology publications 18308684 [PubMed - in process ( Latest neurology publications ) ]

    • Human central nervous system circuits examined through the electrodes implanted for deep brain stimulation.
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      Human central nervous system circuits examined through the electrodes implanted for deep brain stimulation.

      Clin Neurophysiol. 2008 Feb 26;

      Authors: Valls-Solé J, Compta Y, Costa J, Valldeoriola F, Rumià J

      High-frequency repetitive electrical stimulation of deep brain structures through stereotactically implanted electrodes is a well established procedure for symptomatic treatment of patients with Parkinson's disease and other neurological conditions involving dysfunction of basal ganglia circuits. Target nuclei have mainly three structures: the nucleus ventrointermedius externus of the thalamus (Vim), the globus pallidus internum (GPi) and the subthalamic nucleus (STN). Having an electrode implanted in deep brain tissue offers a unique opportunity for carrying out neurophysiological studies on the neural structures and pathways that are within the area of influence of the electrode. This possibility has been used by many researchers in the field that either recorded the activity from, or applied stimulation to, the electrode implanted in the target nuclei. The results of these studies have brought improvement on our knowledge of human brain circuitry and provided cues for understanding better the effects of deep brain stimulation (DBS). We present here a review of the literature on the use of DBS electrodes for externally controlled recording or stimulation. The results reported show some of the possibilities of this new dimension of neurophysiological studies and are, most likely, a preliminary account of future major interventions on human brain.

      PMID:Latest neurology publications 18308626 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Response to Haynes: There's more to deception than brain activity.
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      Response to Haynes: There's more to deception than brain activity.

      Trends Cogn Sci. 2008 Feb 26;

      Authors: Sip KE, Roepstorff A, McGregor W, Frith CD

      PMID:Latest neurology publications 18308618 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Early ventilation in traumatic brain injury.
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      Early ventilation in traumatic brain injury.

      Resuscitation. 2008 Feb 26;

      Authors: Grmec S, Klemen P

      PMID:Latest neurology publications 18308456 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Utilization of a two-standard system in real-time PCR for quantification of gene expression in the brain.
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      Utilization of a two-standard system in real-time PCR for quantification of gene expression in the brain.

      J Neurosci Methods. 2008 Jan 19;

      Authors: Naumenko VS, Osipova DV, Kostina EV, Kulikov AV

      In this study, we applied for real-time PCR the two-standard system that we had worked out previously for PCR with gel-detection of products. Genomic DNA of a known concentration was used as external standard and mRNA of the DNA-dependent RNA-polymerase II was used as internal standard. It was shown that PCR with gel-detection of products and real-time PCR provide similar results and demonstrate almost identical accuracy and repeatability when the two-standard system is used. With the help of the both methods and using the two-standard system we have confirmed the link between the genetically determined freezing reaction in mice and reduced 5-HT(1A) receptor mRNA level in the midbrain. We have also found that the genetically determined freezing reaction in mice is not connected with changes in Tph2 gene expression.

      PMID:Latest neurology publications 18308402 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Mechanisms of ischemic brain damage.
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      Mechanisms of ischemic brain damage.

      Neuropharmacology. 2008 Jan 25;

      Authors: Doyle KP, Simon RP, Stenzel-Poore MP

      In the United States stroke is the third leading cause of death and the leading cause of disability. Brain injury following stroke results from the complex interplay of multiple pathways including excitotoxicity, acidotoxicity, ionic imbalance, peri-infarct depolarization, oxidative and nitrative stress, inflammation and apoptosis. There are very few treatments for stroke and the development of new treatments requires a comprehensive understanding of the diverse mechanisms of ischemic brain damage that are responsible for neuronal death. Here, we discuss the underlying pathophysiology of this devastating disease and reveal the intertwined pathways that are the target of therapeutic intervention.

      PMID:Latest neurology publications 18308346 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • The effect of drilling angle on posterior interosseous nerve safety during open and endoscopic anterior single-incision repair of the distal biceps tendon.
      Related Articles

      The effect of drilling angle on posterior interosseous nerve safety during open and endoscopic anterior single-incision repair of the distal biceps tendon.

      Arthroscopy. 2008 Mar;24(3):305-10

      Authors: Saldua N, Carney J, Dewing C, Thompson M

      Purpose: The purpose of this study was to define a safe trajectory with regard to iatrogenic posterior interosseous nerve (PIN) injury when drilling the bicipital tuberosity for EndoButton repair (Smith & Nephew Endoscopy, Andover, MA) of distal biceps tendon ruptures. Methods: Ten cadaveric forearms were dissected. The bicipital tuberosity was exposed and the biceps tendon detached. The supinator and PIN were exposed dorsally. A K-wire was drilled perpendicular to the surface of the tuberosity. By use of digital calipers, the distance from the exit point of this wire to the PIN was measured. The length of the bone tunnel was also measured. This wire was removed, and a second was drilled from the same starting point but directed 30 degrees ulnarly. Measurements were repeated. A Wilcoxon signed rank test was used to compare the distances of the K-wire to the PIN and the tunnel lengths for both trajectories. Results: With the perpendicular wire, the mean distance to the PIN was 11.1 mm. When directed 30 degrees ulnarly, the mean distance was 16.4 mm. The difference was significant (P < .001). The mean bone tunnel lengths for the 2 trajectories were 17.8 mm and 18.1 mm; this was not found to be significant (P = .508). Conclusions: When drilling the bicipital tuberosity, we advocate starting at a center-center position on the face of the tuberosity, holding the forearm in maximum supination, and aiming 30 degrees ulnarly to decrease the risk to the PIN. This trajectory does not decrease the bone tunnel length available for implants. Clinical Relevance: This cadaveric anatomic study establishes safety from iatrogenic PIN injury during drilling of the bicipital tuberosity for the purpose of open or endoscopic EndoButton repair of distal biceps tendon ruptures.

      PMID:Latest neurology publications 18308182 [PubMed - in process ( Latest neurology publications ) ]

    • Diagnostic imaging practice guidelines for musculoskeletal complaints in adults-an evidence-based approach-part 3: spinal disorders.
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      Diagnostic imaging practice guidelines for musculoskeletal complaints in adults-an evidence-based approach-part 3: spinal disorders.

      J Manipulative Physiol Ther. 2008 Jan;31(1):33-88

      Authors: Bussières AE, Taylor JA, Peterson C

      PURPOSE: To develop evidence-based diagnostic imaging practice guidelines to assist chiropractors and other primary care providers in decision making for the appropriate use of diagnostic imaging for spinal disorders. METHODS: A comprehensive search of the English and French language literature was conducted using a combination of subject headings and keywords. The quality of the citations was assessed using the Quality of diagnostic accuracy studies (QUADAS), the Appraisal of Guidelines Research and Evaluation (AGREE), and the Stroke Prevention and Educational Awareness Diffusion (SPREAD) evaluation tools. The Referral Guidelines for Imaging (radiation protection 118) coordinated by the European Commission served as the initial template. The first draft was sent for an external review. A Delphi panel composed of international experts on the topic of musculoskeletal disorders in chiropractic radiology, clinical sciences, and research were invited to review and propose recommendations on the indications for diagnostic imaging. The guidelines were pilot tested and peer reviewed by practicing chiropractors, and by chiropractic and medical specialists. Recommendations were graded according to the strength of the evidence. RESULTS: Recommendations for diagnostic imaging guidelines of adult spine disorders are provided, supported by more than 385 primary and secondary citations. The overall quality of available literature is low, however. On average, 45 Delphi panelists completed 1 of 2 rounds, reaching more than 85% agreement on all 55 recommendations. Peer review by specialists reflected high levels of agreement, perceived ease of use of guidelines, and implementation feasibility. Dissemination and implementation strategies are discussed. CONCLUSIONS: The guidelines are intended to be used in conjunction with sound clinical judgment and experience and should be updated regularly. Future research is needed to validate their content.

      PMID:Latest neurology publications 18308153 [PubMed - in process ( Latest neurology publications ) ]

    • Therapeutic effects of endothelin-a receptor antagonist on bladder overactivity in rats with chronic spinal cord injury.
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      Therapeutic effects of endothelin-a receptor antagonist on bladder overactivity in rats with chronic spinal cord injury.

      Urology. 2008 Feb;71(2):341-5

      Authors: Ogawa T, Sasatomi K, Hiragata S, Seki S, Nishizawa O, Chermansky CJ, Pflug BR, Nelson JB, Chancellor MB, Yoshimura N

      OBJECTIVES: We investigated the effects of suppression of endothelin-A (ET(A)) receptors on bladder function and ET-1 levels in the bladder in rats with chronic spinal cord injury (SCI). METHODS: We transected the spinal cord of female Sprague-Dawley rats at the level of Th 8-9. Awake cystometrograms were performed 4 weeks after spinal cord transection. We evaluated cystometric parameters such as mean amplitudes of nonvoiding contractions (NVCs), the number of NVCs, voided volume, voiding efficiency, and micturition pressure before and after intravenous (iv) injection of ABT-627, an ET(A) antagonist, or A-19261, an ET(B) antagonist, in SCI animals. Four weeks after spinalization, we also measured the protein and mRNA levels of ET-1 in the bladder using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: ABT-627 (1 mg/kg, iv) but not A-192621 (10 mg/kg, iv) significantly decreased the amplitude of NVCs and the number of NVCs in SCI rats. There were no significant changes in pressure threshold, maximum voiding pressure, voided volume, or voiding efficiency. ELISA analysis for ET-1 showed significantly elevated protein concentrations in SCI rats compared with spinal cord intact rats. Significant upregulation of the ET-1 mRNA was also noted in SCI bladders. CONCLUSIONS: These results suggest that upregulation of ET-1 is involved in the mechanism inducing bladder overactivity in chronic SCI rats, and that an ET(A) receptor antagonist can suppress SCI-induced bladder overactivity as indicated by a reduction in NVCs. Thus, ET(A) receptor inhibition could be an effective treatment for neurogenic bladder overactivity in pathological conditions such as SCI.

      PMID:Latest neurology publications 18308116 [PubMed - in process ( Latest neurology publications ) ]

    • Breast cancer subtypes and survival in patients with brain metastases.
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      Breast cancer subtypes and survival in patients with brain metastases.

      Breast Cancer Res. 2008 Feb 28;10(1):R20

      Authors: Nam BH, Kim SY, Han HS, Kwon Y, Lee KS, Kim TH, Ro J

      ABSTRACT: INTRODUCTION: Brain metastases (BM) occur in up to one third of patients with metastatic breast cancer (MBC), whose incidences and prognoses by breast cancer subtypes in BM have not been well delineated. METHODS: Retrospective survival analyses were performed in 126 BM patients from 805 MBC patients treated at the National Cancer Center between August 2001 and April 2006, according to clinical characteristics, breast cancer subtypes, and receipt of trastuzumab. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor-2 (HER2) statuses were tested by immunohistochemical (IHC) staining, and HER2 FISH analysis conducted for IHC 2+. RESULTS: The proportion of HER2+/ER- (29% vs 16%) and triple-negative (37% vs 25%) tumors was higher in the 126 BM patients than those without BM. While median survival after recurrence was longer in patients with luminal A disease (median survival of luminal A vs luminal B vs HER2+/ER- vs triple-negative: p = 0.0246; 39.6 vs 27.4 vs 20.9 vs 15.5 months), survival was shorter from BM to death in luminal A and triple negatives (median survival: p = 0.0113; 4.0 vs 9.2 vs 5.0 vs 3.4 months). Receipt of trastuzumab after BM was a significant variable for survival in HER2+ patients. Multivariate analyses identified ER-negative, HER2-negative, or triple-negative, as well as older age, presence of leptomeningeal disease, and three or more extracranial disease sites, as poor prognostic factors for survival after BM. CONCLUSIONS: MBC patients who developed BM had higher proportions of triple-negative and HER2+/ER- tumor status. Triple receptor status is a useful prognostic marker for predicting survival after BM in metastatic breast cancer patients.

      PMID:Latest neurology publications 18307763 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Baroreflex control of sympathetic nerve activity and blood pressure variability.
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      Baroreflex control of sympathetic nerve activity and blood pressure variability.

      Clin Exp Pharmacol Physiol. 2008 Apr;35(4):512-5

      Authors: Julien C

      1. The simultaneous recording of blood pressure (BP) and renal sympathetic nerve activity (RSNA) in conscious sinoaortic baroreceptor denervated rats has revealed that the sympathetic component of the baroreceptor reflex both limits the amplitude of slow BP fluctuations and generates a faster BP oscillation (~0.4 Hz in rats), the so-called Mayer wave. 2. Using BP and RSNA time series collected in conscious baroreceptor denervated rats and parameters of the transfer function relating RSNA to BP, it has been possible to predict BP and RSNA variabilities actually observed in baroreceptor-intact rats. The most accurate simulation was obtained when the baroreflex gain was set at 20-30% of a critical value leading to the production of self-sustained oscillations of BP and RSNA at Mayer wave's frequency. 3. Recent studies performed on conscious rats have indicated that the gain of the RSNA-BP baroreflex function curve is altered during sleep-wake cycle, grooming, exercise and exposure to environmental stress. These observations raise the possibility that the sympathetic baroreflex sensitivity might be continuously modulated as part of normal behavioural responses. 4. To examine this hypothesis, a method has been developed to obtain a continuous index of sympathetic baroreflex sensitivity. The method is based on the calculation of the gain of the transfer function relating RSNA oscillations to the BP pulse at heart rate frequency. This new spontaneous index correlates with the baroreflex gain measured by the vasoactive drug injection technique and is inversely related to overall indices of BP variability. In addition, it shows large, spontaneous variations over time.

      PMID:Latest neurology publications 18307752 [PubMed - in process ( Latest neurology publications ) ]

    • Metabotropic neurotransmission and integration of sympathetic nerve activity by the rostral ventrolateral medulla in the rat.
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      Metabotropic neurotransmission and integration of sympathetic nerve activity by the rostral ventrolateral medulla in the rat.

      Clin Exp Pharmacol Physiol. 2008 Apr;35(4):508-11

      Authors: Pilowsky PM, Abbott SB, Burke PG, Farnham MM, Hildreth CM, Kumar NN, Li Q, Lonergan T, McMullan S, Spirovski D, Goodchild AK

      1. Cardiovascular sympathetic nerve activity at rest is grouped into waves, or bursts, that are generally, although not exclusively, related to the heart rate and to respiration. In addition, activity is also generated in response to central commands and to environmental stimuli. 2. Responsibility for the integration of all these different elements of sympathetic activity rests with pre-motoneurons in the rostral ventrolateral medulla oblongata. These pre-motoneurons are glutamatergic and spinally projecting where they form synapses with sympathetic preganglionic neurons. 3. Pre-motoneurons also contain and presumably release, neurotransmitters other than glutamate, including amines and neuropeptides that act on metabotropic receptors with long-term effects on cell function. 4. Similarly, in the rostral ventrolateral medulla oblongata the pre-motoneurons are mainly regulated by excitatory influences from glutamate and inhibitory influences from gamma-aminobutyric acid (GABA). Major focuses of recent studies are the interactions between non-glutamatergic and GABAergic systems and reflexes that regulate the activity of the sympathetic nervous system. 5. The results indicate that neurotransmitters acting at metabotropic receptors selectively affect different reflexes in the rostral ventrolateral medulla. It is suggested that this differential activation or attenuation of reflexes by different neurotransmitters is a mechanism by which the organism can fine-tune its responses to different homeostatic requirements.

      PMID:Latest neurology publications 18307751 [PubMed - in process ( Latest neurology publications ) ]

    • Risk of dementia associated with the ApoE epsilon4 allele and falls causing head injury without explicit traumatic brain injury.
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      Risk of dementia associated with the ApoE epsilon4 allele and falls causing head injury without explicit traumatic brain injury.

      Acta Neurol Scand. 2008 Feb 26;

      Authors: Luukinen H, Jokelainen J, Kervinen K, Kesäniemi YA, Winqvist S, Hillbom M

      Objectives - Severe head injury (HI) and the apolipoprotein E (ApoE) epsilon4 allele are risk factors for dementia. The corresponding effect of falls causing HI without explicit traumatic brain injury (TBI) in association with the ApoE epsilon4 is not known. Materials and methods - Altogether 134 persons aged 70 years or older constituted a retrospective population sample, who scored >/=26 in the MiniMental State Examination (MMSE) test at baseline and were clinically examined for dementia 9 years afterward. Fall-related HI causing superficial laceration or bruises or wounds that require suturing were prospectively recorded during the 9-year follow-up. We used Cox regression with age at the diagnosis of dementia as a dependent variable. Results - Twenty-eight (21%) subjects had falls causing HI without explicit TBI, the ApoE epsilon4 allele was seen in 44 (33%), and clinical dementia was diagnosed in 25 (19%). Adjusted for the baseline MMSE score, sex and educational status, the hazard ratio for subsequent dementia in subjects having falls with HI without explicit TBI and the ApoE epsilon4 allele as compared with those who do not possess these characteristics was 2.70 (95% confidence interval, 1.02-7.16). Conclusions - According to the results of this small retrospective study, falls with HI without explicit TBI in connection with the ApoE epsilon4 allele is associated with subsequent dementia among older adults.

      PMID:Latest neurology publications 18307571 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Trigeminal nasal-specific neurons respond to nerve growth factor with substance-P biosynthesis.
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      Trigeminal nasal-specific neurons respond to nerve growth factor with substance-P biosynthesis.

      Clin Exp Allergy. 2008 Feb 25;

      Authors: Mingomataj E, Dinh QT, Groneberg D, Feleszko W, Schmeck B, Joachim R, Noga O, Nagel S, Klapp BF, Fischer A

      Background Nerve growth factor (NGF) has been found to induce substance-P biosynthesis in large-diameter A-fibres vagal airway neurons. However, the effect of NGF on trigeminal neurons innervating the nasal mucosa of the mouse has not been investigated so far. Objective NGF has been implicated in allergic diseases by modulating sensory nerves. Therefore, the present study investigated the effect of NGF on neuropeptides expression such as substance-P and glutamate in nasal trigeminal neurons. Methods Using neuronal tracing in combination with double labelling immunohistochemistry the expression of substance-P, glutamate and neurofilament protein 68-kDa expression was examined in nasal-specific trigeminal neurons of BALB/c-mice. Results The numbers of Fast blue-labelled trigeminal neurons expressing substance-P were significantly increased after NGF exposure (NGF-treated ganglia: 16.4 +/- 0.6% vs. control: 7.0 +/- 0.4%, P</=0.001). NGF treatment-induced substance-P biosynthesis in neurofilament-positive (NGF-treated ganglia: 8.6 +/- 0.2% vs. control: 1.1 +/- 0.2%, P</=0.001) as well as neurofilament-negative (NGF-treated ganglia: 7.8 +/- 0.6% vs. control: 5.9 +/- 0.4%, P=0.05) and non-glutamatergic neurons (NGF-treated ganglia: 11.8 +/- 1.9% vs. control 1.1 +/- 1.0%, P</=0.001) 24 h after NGF exposure. Conclusion Under normal conditions, substance-P was expressed in nasal-specific neurofilament-negative, glutamatergic and C-fibre neurons. Nasal-specific trigeminal neurons respond to NGF treatment with substance-P biosynthesis in non-glutamatergic, neurofilament-positive as well as -negative neurons. These findings suggest that nasal-specific trigeminal neurons are composed of heterogenous subpopulations in relation to their peptide profiles and therefore may have different functions in neurogenic airway inflammation.

      PMID:Latest neurology publications 18307524 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Photo-Cross-Linked Hybrid Polymer Networks Consisting of Poly(propylene fumarate) and Poly(caprolactone fumarate): Controlled Physical Properties and Regulated Bone and Nerve Cell Responses.
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      Photo-Cross-Linked Hybrid Polymer Networks Consisting of Poly(propylene fumarate) and Poly(caprolactone fumarate): Controlled Physical Properties and Regulated Bone and Nerve Cell Responses.

      Biomacromolecules. 2008 Feb 29;

      Authors: Wang S, Kempen DH, Simha NK, Lewis JL, Windebank AJ, Yaszemski MJ, Lu L

      Aiming to achieve suitable polymeric biomaterials with controlled physical properties for hard and soft tissue replacements, we have developed a series of blends consisting of two photo-cross-linkable polymers: polypropylene fumarate (PPF) and polycaprolactone fumarate (PCLF). Physical properties of both un-cross-linked and UV cross-linked PPF/PCLF blends with PPF composition ranging from 0% to 100% have been investigated extensively. It has been found that the physical properties such as thermal, rheological, and mechanical properties could be modulated efficiently by varying the PPF composition in the blends. Thermal properties including glass transition temperature ( T g) and melting temperature ( T m) have been correlated with their rheological and mechanical properties. Surface characteristics such as surface morphology, hydrophilicity, and the capability of adsorbing serum protein from culture medium have also been examined for the cross-linked polymer and blend disks. For potential applications in bone and nerve tissue engineering, in vitro cell studies including cytotoxicity, cell adhesion, and proliferation on cross-linked disks with controlled physical properties have been performed using rat bone marrow stromal cells and SPL201 cells, respectively. In addition, the role of mechanical properties such as surface stiffness in modulating cell responses has been emphasized using this model blend system.

      PMID:Latest neurology publications 18307311 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Regional apparent metabolite concentrations in young adult brain measured by (1)H MR spectroscopy at 3 Tesla.
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      Regional apparent metabolite concentrations in young adult brain measured by (1)H MR spectroscopy at 3 Tesla.

      J Magn Reson Imaging. 2008 Feb 28;27(3):489-499

      Authors: Baker EH, Basso G, Barker PB, Smith MA, Bonekamp D, Horská A

      PURPOSE: To quantify and examine the distribution of brain metabolites in normal young adults using single voxel MR spectroscopy at 3 Tesla (T). MATERIALS AND METHODS: Short-echo time single-voxel PRESS technique was used to measure the apparent concentration of five metabolites at nine locations in the brains of young adults. Concentrations were estimated by means of an automated fitting method (LCModel) with reference to an unsuppressed water signal and were corrected for T(1) relaxation, T(2) relaxation, and cerebrospinal fluid partial volume. Analysis of variance with Tukey post hoc test was used to evaluate regional variations. RESULTS: Statistically significant differences in regional concentrations were detected for each of the metabolites. The number of significant differences was greatest for total choline, whereas myo-inositol and the sum of glutamine and glutamate had the fewest. Magnitude of variation was greatest for total choline and least for the sum of N-acetyl aspartate and N-acetylaspartylglutamate. CONCLUSION: In agreement with previous studies at other field strengths, we found heterogeneous distribution of the major spectroscopically measurable brain metabolites. Although the most distinct differences are between tissue types, there is appreciable variation within a tissue type at different locations. The spectra and metabolite concentrations presented should provide a useful reference for both clinical and research MR spectroscopy studies performed at 3T. J. Magn. Reson. Imaging 2008;27:489-499. (c) 2008 Wiley-Liss, Inc.

      PMID:Latest neurology publications 18307197 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Effect of dehydroepiandrosterone (DHEA) on monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in aging rat brain regions.
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      Effect of dehydroepiandrosterone (DHEA) on monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in aging rat brain regions.

      Biogerontology. 2008 Feb 29;

      Authors: Kumar P, Taha A, Sharma D, Kale RK, Baquer NZ

      Dehydroepiandrosterone (DHEA), one of the major steroid hormones, and its ester have recently received attention with regard to aging and age-related diseases like Alzheimer and others. DHEA is synthesized de novo in the brain and its substantial fall with age has been shown to be associated with neuronal vulnerability to neurotoxicity processes. Thus, DHEA is considered to be a neuroactive pharmacological substance with potential antiaging properties. A prominent feature that accompanies aging is an increase in monoamine oxidase (MAO). Increased MAO activity with correlated increase in lipid peroxidation in the aging rat brain supports the hypothesis that catecholamine oxidation is an important source of oxidative stress. The progressive accumulation of lipofuscin in neuronal cells is one of the most characteristic age related changes, an increase in body weight was also observed at 24 months. The objective of this study was to observe the changes in monoamine oxidase activity, lipid peroxidation levels and lipofuscin accumulation occurring in aging rat brain regions, and to see whether these changes are restored to normal levels after exogenous administration of DHEA (30 mg/kg/day for 1 month). The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, lipid peroxidation levels and lipofuscin accumulation in brain regions of 4, 14 and 24 months age group male rats. The present study showed that DHEA treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, the increased body weight at 24 months also decreased more than the age matched controls. It can therefore be suggested that DHEA's beneficial effects seemed to arise from its antioxidant, antiobesity, antilipofuscin, antilipidperoxidative and thereby anti-aging actions. The results of this study will be useful for pharmacological modification of the aging process and development of new drugs for age related disorders.

      PMID:Latest neurology publications 18307051 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Spatiotemporal Patterns of SSeCKS Expression After Rat Spinal Cord Injury.
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      Spatiotemporal Patterns of SSeCKS Expression After Rat Spinal Cord Injury.

      Neurochem Res. 2008 Feb 29;

      Authors: Xiao F, Fei M, Cheng C, Ji Y, Sun L, Qin J, Yang J, Liu Y, Zhang L, Xia Y, Shen A

      Src suppressed C kinase substrate (SSeCKS) was identified as a PKC substrate/PKC-binding protein, which plays a role in mitogenic regulatory activity and has a function in the control of cell signaling and cytoskeletal arrangement. However its distribution and function in the central nervous system (CNS) lesion remain unclear. In this study, we mainly investigated the mRNA and protein expression and cellular localization of SSeCKS during spinal cord injury (SCI). Real-time PCR and Western blot analysis revealed that SSeCKS was present in normal whole spinal cord. It gradually increased, reached a peak at 3 days for its mRNA level and 5 days for its protein level after SCI, and then declined during the following days. In ventral horn, the expression of SSeCKS underwent a temporal pattern that was similar with the whole spinal cord in both mRNA and protein level. However, in dorsal horn, the mRNA and protein for SSeCKS expression were significantly increased at 1 day for its mRNA level and 3 days for its protein level, and then gradually declined to the baseline level, ultimately up-regulated again from 7 to 14 days. The protein expression of SSeCKS was further analysed by immunohistochemistry. The positively stained areas for SSeCKS changed with the similar pattern to that of protein expression detected by immunoblotting analysis. Double immunofluorescence staining showed that SSeCKS immunoreactivity (IR) was found in neurons, astrocytes, oligodendrocytes of spinal cord tissues within 5 mm from the lesion site. Importantly, injury-induced expression of SSeCKS was co-labeled by active caspase-3 (apoptotic marker), Tau-1 (the marker for pathological oligodendrocyte) and beta-1,4-galactosyltransferase 1 (GalT). All the results suggested that SSeCKS might play important roles in spinal cord pathophysiology and further research is needed to have a good understanding of its function and mechanism.

      PMID:Latest neurology publications 18307037 [PubMed - as supplied by publisher - ( Latest neurology publications ) ]

    • Prevention of reperfusion injury of the spinal cord in aortic surgery: An experimental study.
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      Prevention of reperfusion injury of the spinal cord in aortic surgery: An experimental study.

      Surg Today. 2008;38(3):237-44

      Authors: Koçogullari CU, Becit N, Erkut B, Keleş MS, Ceviz M, Ates A, Gündoğdu C, Kaygin MA, Koçak H

      PURPOSE: We designed an experimental study to show the effects of some agents in order to prevent reperfusion injury of the spinal cord. METHODS: Twenty rabbits were used and were divided into two groups in our study. Infrarenal abdominal aortic occlusion, between renal arteries and iliac bifurcations, was applied to the subjects in group 1 for only 30 min; in the group 2 subjects, on the other hand, intra-aortic diltiazem, N-acetylcysteine, and catalase combinations were applied after infrarenal abdominal aortic occlusion. The spinal cord functions of the subjects were assessed at the 48th hour after the operation according to Tarlov scoring, then cord tissue samples were taken for biochemical and histopathological studies. RESULTS: The group 2 subjects had better neurological functions than group 1 subjects (P < 0.01). In group 2; superoxide dismutase and glutathione peroxidase levels increased, while malondialdehyde and xanthine oxidase levels decreased as compared with group 1 (P < 0.05). A histopathological examination showed the group 2 samples to have fewer bleeding points and less neuron loss. CONCLUSIONS: We concluded that antioxidant agent combinations (diltiazem, N-acetylcysteine, and catalase) applied after ischemia might thus help protect the spinal cord against ischemia and reperfusion injury.

      PMID:Latest neurology publications 18306998 [PubMed - in process ( Latest neurology publications ) ]

    • [Effect of total saponins of Rubus parviflolius (TSRP) on change of hydrated amount and blood-brain barrier in rats during focal cerebral ischemic/reperfusion]
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      [Effect of total saponins of Rubus parviflolius (TSRP) on change of hydrated amount and blood-brain barrier in rats during focal cerebral ischemic/reperfusion]

      Zhongguo Zhong Yao Za Zhi. 2007 Oct;32(20):2166-9

      Authors: Wang JS, Qiu ZY, Li HZ, Xia YP, Zhou CL

      OBJECTIVE: To explore the effects of total saponins of Rubus parviflolius (TSRP) on brain edema and blood brain barrier in rats. METHOD: The model of local cerebral ischemia was established in rats by reversible inserting a nylon thread into the anterior cerebral artery through the internal carotid artery brain hydrated amount and content change of Evan' s blue (EB) in cortex subjected to 2h middle cererbral artery occlusion (MACO) followed by 6 h, 24 h, 48 h, 72 h reperfusion and effect of TSRP. penetrability of blood brain-barrier (BBB) the index includes brain hydrated amount and penetrability of blood brain-barrier BBB. RESULT: Com- pared with I/R group. Both brain hydrated amount and the EB content decreased significantly in TSRP groups on the 6 h, 24 h, 48 h, 72 h of reperfusion after 2 hour of cerebral ischemia induced by MACO model. CONCLUSION: TSRP could decrease brain hydrated amount and markedly lower permeability of blood-brain barrier subjected to 2 h MACO followed by 24 h reperfusion, and this may be a mechanism of TSRP alleviating brain edema during I/R.

      PMID:Latest neurology publications 18306754 [PubMed - in process ( Latest neurology publications ) ]

    • [Deltaran effect on the mediatory balance of young and old rats' brain with left-side profile in case of carotid arteries occlusion]
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      [Deltaran effect on the mediatory balance of young and old rats' brain with left-side profile in case of carotid arteries occlusion]

      Adv Gerontol. 2007;20(2):138-42

      Authors:

      The medico-social significance of ischemic brain lesions, which are the most frequent cause of disablement and death in older people, stipulates the need for efficient means of prevention and correction of central nervous system disorders in case of ischemic brain lesions. The efficacy of Deltaran in the correction of disordered neuromediator balance in the brain of rats of different age groups was studied on the model of carotid arteries occlusion. Studies showed, that Deltaran exerts an anti-stress effect on old rats with left-side profile by altering the neuromediators' distribution in animals' brain under conditions of hypoxia. This enables to recommend Deltaran for further study as a neuroprotector.

      PMID:Latest neurology publications 18306704 [PubMed - in process ( Latest neurology publications ) ]

    • [A case of hypokalemic myopathy mimicking hemiparesis]
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      [A case of hypokalemic myopathy mimicking hemiparesis]

      Brain Nerve. 2008 Feb;60(2):191-4

      Authors: Yaguchi M, Yaguchi H, Sakano M

      We report the case of an 86-year-old female with licorice-induced hypokalemic myopathy. For four years, she had been taking two kinds of Chinese medicines containing licorice. The patient presented with difficulty in holding her head up and proximal-dominant tetraparesis with significant laterality. In manual muscle tests, the right extremities showed grade 2/5 and the left extremities, grade 4/5. The general reflexes were decreased, and the bilateral Chaddock's reflexes were repeatedly positive. The sensory, cerebellar and autonomic systems were normal and discrete movements of all extremities were well preserved. Laboratory tests showed elevated levels of CK (559 IU/1), hypokalemia (1.6 mEq/1), and metabolic alkalosis (pH 7.51, base excess 10.9 mmol/1). Magnetic resonance