Restorative Neurology and Neuroscience - Volume 26, issue 1

Authors: Nys, G.M.S. | de Haan, E.H.F. | Kunneman, A. | de Kort, P.L.M. | Dijkerman, H.C.

Article Type: Research Article

Abstract: Purpose: At present, prism adaptation is probably the most promising rehabilitation procedure for hemi-neglect. However, randomised controlled trials are lacking and no data are available on the effectiveness of prism adaptation in the treatment of acute neglect. Methods: We followed sixteen neglect patients using a randomised controlled design in which six patients received four-day-in-a-row placebo treatment (CG) and ten patients received four-day-in-a row experimental treatment with 10° rightward deviating prisms …(EG) during their stay on the stroke unit. We examined whether patients in the EG improved faster than the CG by administering three neglect tasks (Schenkenberg Line Bisection, Letter Cancellation, Gainotti Scene Copying) immediately before and after each treatment. Second, we examined whether patients in the EG demonstrated a better long-term outcome at one month post-treatment (Behavioural Inattention Test). Results: Patients in the EG improved faster on spatial tasks (line bisection, cancellation) than the CG but not on visuo-construction. Patients in the EG showed no differences with the CG in neglect outcome at one month post-treatment. Conclusions: Four consecutive prism sessions produced beneficial effects in patients with acute neglect. However, prism effects were either short-term, or placebo treatment with repeated pointing and/or repeated neglect testing was more helpful than we anticipated. Our results emphasize the importance of a placebo condition and a follow-up in rehabilitation studies. Show more

Keywords: Neglect, randomised placebo-controlled trial, acute, prism adaptation, repetitive

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 1, pp. 1-12, 2008

Authors: Mark, Victor W. | Taub, Edward | Perkins, Christi | Gauthier, Lynne | Uswatte, Gitendra

Article Type: Research Article

Abstract: Purpose: To evaluate the effect of total cerebral infarction volume on motor status and treatment responses to Constraint-Induced Movement therapy (CI therapy) in patients with chronic post-stroke hemiparesis and limb nonuse. In most studies of clinical-radiological correspondences, infarct volume has been found to predict clinical status. Methods: 60 adult patients who met inclusion criteria for CI therapy underwent standard structural brain MRI around the time of treatment. We tested whether the total volume of …infarcted tissue predicted pre-treatment values and pre- to post-treatment changes on standard assessments of laboratory- and real-world-based upper extremity movement. Results: The patients significantly improved from baseline clinical motor measures after CI therapy. The range of infarction volumes was comparable to those of other stroke studies. In contrast, total infarction volume was not correlated with any of the motor measures. The absence of correlation was maintained even when evaluating only patients with either unilateral or solitary cerebral infarctions, or with respect to severity of baseline motor impairment or variations in the forms of therapy. Conclusion: The findings suggest that certain standard motor measures in chronic hemiparetic stroke (limb movement in the laboratory, limb use in the life situation, changes in these measures following efficacious CI therapy) are insensitive to infarction load. Our findings are consistent with the hypothesis that plastic brain reorganization after stroke attenuates the effect of infarct volume on purposive limb movement. However, we cannot exclude the possibilities that the specific methods we used to assess upper limb status may be generally insensitive to infarction load, or that the stringent inclusion criteria for this research precluded detecting an effect of infarction load. Further study to evaluate these relationships in the acute-subacute stroke phases and among patients with more severe motor deficits would help to clarify the basis for the lack of an infarction load effect. Show more

Keywords: Cerebrovascular accident, rehabilitation, magnetic resonance imaging, neuronal plasticity, movement, diagnostic imaging

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 1, pp. 13-33, 2008

Authors: Grivennikov, Igor A. | Dolotov, Oleg V. | Zolotarev, Yuri A. | Andreeva, Ludmila A. | Myasoedov, Nikolai F. | Leacher, Lauren | Black, Ira B. | Dreyfus, Cheryl F.

Article Type: Research Article

Abstract: PURPOSE. It is well established that cholinergic neurons of the basal forebrain degenerate in Alzheimer's dementia. Although recent studies were concentrated on screening molecules that might reduce the concomitant cell loss, little is known about therapeutically promising molecules. We studied the effect of Semax (Met-Glu-His-Phe-Pro-Gly-Pro), a behaviorally active adrenocorticotropic hormone (4–10) analogue, on survival of cholinergic basal forebrain neurons in vitro. Semax is known to stimulate learning and memory and can …be successfully used for treatment of ischemic stroke. METHODS. Primary cultures of neuronal and glial cells from basal forebrain of rats were used in all experiments. The stability of Semax in cell cultures was tested by HPLC analysis. Cell survival in neuronal cultures was quantitated using immocytochemical and cytochemical analyses as well as detection of choline acetyltransferase activity. RESULTS. We have shown that Semax may approximately 1.5–1.7 fold increase survival of cholinergic basal forebrain neurons in vitro. Moreover, Semax (100 nM) stimulated activity of choline acetyltransferase in dissociated basal forebrain tissue cultures. However, the numbers of GABA-ergic neurons, total neuron specific enolase neurons were not affected. In concentration from 1 nM to 10 μM, Semax did not affect proliferation of glial cells in primary cultures. CONCLUSION. Implications of these findings with respect to Alzheimer's disease remain to be clarified. Show more

Keywords: ACTH(4-10) analog, basal forebrain, cholinergic neurons, survival, CAT-activity, GABA staining, AchE staining, Alzheimer's disease

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 1, pp. 35-43, 2008

Authors: Conte, Valeria | Raghupathi, Ramesh | Watson, Deborah J. | Fujimoto, Scott | Royo, Nicolas C. | Marklund, Niklas | Stocchetti, Nino | McIntosh, Tracy K.

Article Type: Research Article

Abstract: Purpose: The ability of brain-derived neurotrophic factor (BDNF) to attenuate secondary damage and influence behavioral outcome after experimental traumatic brain injury (TBI) remains controversial. Because TBI can result in decreased expression of the trkB receptor, thereby preventing BDNF from exerting potential neuroprotective effects, the contribution of both BDNF and its receptor trkB to hippocampal neuronal loss and cognitive dysfunction were evaluated. Methods: Full-length trkB was overexpressed in the left hippocampus …of adult C57Bl/6 mice using recombinant adeno-associated virus serotype 2/5 (rAAV 2/5). EGFP (enhanced green fluorescent protein) expression was present at two weeks after AAV-EGFP injection and remained sustained up to four weeks after the injection. At 2 weeks following gene transduction, mice were subjected to parasagittal controlled cortical impact (CCI) brain injury, followed by either BDNF or PBS infusion into the hippocampus. Results: No differences were observed in learning ability at two weeks post-injury or in motor function from 48 hours to two weeks among treatment groups. The number of surviving pyramidal neurons in the CA2-CA3 region of the hippocampus was also not different among treatment groups. Conclusions: These data suggest that neither overexpression of trkB, BNDF infusion or their combination affects neuronal survival or behavioral outcome following experimental TBI in mice. Show more

Keywords: Adeno-associated virus, cell death, cognition, in vivo gene therapy, neurotrophins

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 1, pp. 45-56, 2008

Authors: Weise, Jens | Doeppner, Thorsten R. | Müller, Tilo | Wrede, Arne | Schulz-Schaeffer, Walter | Zerr, Inga | Witte, Otto W. | Bähr, Mathias

Article Type: Research Article

Abstract: Purpose: The physiological function of the cellular prion protein (PrP^{C} ) is still unclear. A growing body of evidence suggests that PrP^{C} has neuroprotective properties and that its deletion increases susceptibility to focal cerebral ischemia. The purpose of this study was to elucidate the role of PrP^{C} overexpression in ischemic brain injury in vivo. Methods: PrP^{C} overexpressing (TG35) and wild type (WT) mice were subjected to a …90-minute transient focal cerebral ischemia followed by infarct volume analysis 24 hours after lesion. To identify effects of PrP^{C} overexpression on signalling pathways important for the regulation of ischemic cell death, we studied postischemic activation and expression of Akt and Erk1/2 using quantitative Western Blot analysis. Results: TG35 mice displayed significantly smaller infarct volumes and showed reduced early postischemic Erk1/2 phosphorylation, a pathway known to exacerbate neuronal injury following transient cerebral ischemia. In contrast, PrP^{C} overexpression did not change postischemic Akt phosphorylation, which acts anti-apoptotic and is reduced in PrP^{C} knockout animals. Conclusions: These results demonstrate that PrP^{C} overexpression reduces deleterious Erk1/2 activation but does not affect Akt activation after transient cerebral ischemia, suggesting a role for distinct cytosolic signalling pathways in PrP^{C} mediated neuroprotection. Show more

Keywords: Prion protein, cerebral ischemia, Erk1/2, Akt, neuroprotection

Citation: Restorative Neurology and Neuroscience, vol. 26, no. 1, pp. 57-64, 2008