Restorative Neurology and Neuroscience - Volume 22, issue 2

Authors: Jang, Sung Ho | Kim, Yun-Hee | Chang, Yongmin | Han, Bong Soo | Byun, Woo Mok | Chang, Chul Hoon

Article Type: Research Article

Abstract: Purpose: Contralateral primary sensori-motor cortex (SM1) activation by passive movement was investigated by functional MRI (fMRI) at the early stage of stroke, to determine whether SM1 activation can be used to predict the degree of motor recovery of the hemiplegic hand. Methods: We studied 17 stroke patients who showed complete paralysis of a hemiplegic hand at onset. The motor function of the hemiplegic hand was assessed on 4 separate occasions (at onset, at fMRI evaluation (performed …< 4 weeks after onset), and 3 and 6 months after onset). Significant motor recovery was defined as recovery of the affected hand to the extent of it being able to prehend an object against gravity at least at 6 months after onset. Results: The patients having an activated contralateral SM1 showed better motor recovery than those who did not. Only a fourth of the patients with an activated contralateral SM1 experienced a significant motor recovery, whereas none of the patients with an inactivated SM1 showed an improvement 6 months after onset, however, the incidence of significant motor recovery was not significantly difference between the two groups. Conclusions: It appears that contralateral SM1 activation by passive movement in the early stage of stroke has a low predictive value for the motor recovery of the hemiplegic hand, because the activation of the contralateral SM1 by passive movement appears to be mediated by somatosensory input to the cortex from the thalamus rather than from the motor pathway. Show more

Keywords: functional magnetic resonance imaging, motor recovery, hemiplegia, stroke

Citation: Restorative Neurology and Neuroscience, vol. 22, no. 2, pp. 59-63, 2004

Authors: Scherman, Peter | Kanje, Martin | Dahlin, Lars B.

Article Type: Research Article

Abstract: Purpose: To compare the longitudinal suture model for bridging nerve defects with direct approximation under tension or with autologuos nerve grafting. Methods: Seven mm nerve defects in the rat sciatic nerve were repaired by either of these three methods. Evaluation was performed at twelve weeks by morphometry of the tibial nerve distal to the repair site and by weight of the gastrocnemius muscle, an indicator of target reinnervation. Results: The number of nerve fibers and myelin …areas in the tibial nerve were similar for all repair methods as were the weight of the gastrocnemius muscle. Conclusions: Longitudinal sutures can be used to bridge short nerve defects and could be an alternative to nerve grafting. Show more

Keywords: nerve repair, nerve regeneration, tension, suture, nerve graft, muscle weight, axonal counts

Citation: Restorative Neurology and Neuroscience, vol. 22, no. 2, pp. 65-72, 2004

Authors: Lenzlinger, Philipp M. | Saatman, Kathryn E. | Hoover, Rachel C. | Cheney, Jessica A. | Bareyre, Florence M. | Raghupathi, Ramesh | Arnold, Lee D. | McIntosh, Tracy K.

Article Type: Research Article

Abstract: Purpose: In the present study we assessed the ability of BSF476921, an inhibitor of vascular endothelial growth factor receptor (VEGFR) kinase signal transduction, to reduce edema formation and neurologic motor dysfunction following lateral fluid percussion (FP) brain injury in rats. Methods: Anesthetized adult male rats were subjected to either lateral FP brain injury of moderate severity (n = 37) or sham injury (n = 22, surgery without brain injury). Animals were randomized to receive i.p. …injections of either BSF476921 (30 mg/kg bw; injured n = 15, sham n = 11) or sterile water (injured n = 14, sham n = 11) at 1, 11 and 22 hours post-injury. After assessment of motor function using a standard 28-point neuroscore, animals were sacrificed 24 hours following trauma and their brains evaluated for regional water content using the wet-weight/dry-weight technique. Results: Although brain-injured animals showed a significant motor deficit compared to uninjured animals, no differences were detected between BSF476921- and vehicle-treated animals at the acute 24 hour post-injury time point. However, BSF476921 significantly attenuated regional edema formation in brain-injured animals in the ipsilateral hippocampus (p < 0.05) and in the cortex adjacent to the injury (p < 0.05) when compared to vehicle treatment. Conclusions: To our knowledge, this is the first report of a small molecule VEGFR kinase inhibitor reducing cerebral edema in a widely accepted model of brain injury. Show more

Keywords: blood brain-barrier, cerebral edema, head injury, neuromotor function

Citation: Restorative Neurology and Neuroscience, vol. 22, no. 2, pp. 73-79, 2004

Authors: Skvortsova, V.I. | Slominsky, P.A. | Gubskii, L.V. | Koltsova, E.A. | Shetova, I.M. | Platonova, I.A. | Tupitsyna, T.I. | Khrunin, A.V. | Limborska, S.A.

Article Type: Research Article

Abstract: Purpose: The aim of our investigation was to study the connection between p53 gene Bam HI RFLP polymorphism and the brain infarction volume in patients with atherothrombotic ischemic stroke that could highlight certain genetic aspects of the individual sensibility of brain tissue to acute ischemia. Materials and Methods: Diallelic Bam HI RFLP polymorphism in 5' flanking region p53 gene was studied in 96 patients with carotid atherothrombotic stroke from Moscow population. Magnetic resonance imaging …was conducted on day 7 after the stroke onset. The manual morphometry and "Osiris" morphometric hardware (by the Hospital of the University of Geneva) were used for assessment of the infarction volume. Results: The predominance of small-size infarctions (< 40 cm^3 ) was revealed in patients with (-/-) Bam HI RFLP p53 genotype versus patients with (-/+) (χ^2 = 19.7; P < 0.001) and (+/+) (χ^2 = 12.288; P < 0.001) genotypes. According to the Bayesian's statistics, in patients with (-/-) p53 Bam HI genotype the development of a small-size infarction in atherothrombotic ischemic stroke can be prognosticated with probability more than 65%. Conclusions A significant association between p53 gene Bam HI RFLP polymorphism and the infarction volume was found in patients with carotid atherothrombotic stroke from Moscow population. These results additionally confirm that apoptosis plays an important role in the formation of ischemic brain lesion and that drugs with anti-apoptotic properties may prove beneficial in stroke patients. Show more

Keywords: cerebral ischemia, atherothrombotic stroke, p53 gene, infarction volume

Citation: Restorative Neurology and Neuroscience, vol. 22, no. 2, pp. 81-85, 2004

Authors: Maiese, Kenneth | Chong, Zhao Zhong

Article Type: Research Article

Abstract: Purpose: Since the description of his original patient Auguste D. with cognitive disability, Alois Alzheimer persisted in his clinical investigations to understand this complex disease. Although more than a century later the underlying cellular dysfunctions that can initiate and determine the course of this neurodegenerative disease remain evasive, significant strides continue to elucidate the complex nature of Alzheimer dementia and define potential effective strategies for its prevention and treatment. Methods and results: In this …article, we examine the cellular mechanisms that define Alzheimer disease. They are diverse in nature and involve pathways of oxidative stress that extend well beyond the pathological hallmarks of β-amyloid aggregates and neurofibrillary tangles. Oxidative stress precipitates both nuclear DNA degradation and membrane phosphatidylserine exposure in neuronal and vascular cells to promote loss of cellular integrity, microglial phagocytosis, and thrombotic destruction. Critical in the ability to foster cell survival during oxidative stress is the modulation of the metabotropic glutamate system, cell cycle regulation in post-mitotic neurons, and control of GSK-3β activity and presenilin integrity. These cellular pathways ultimately converge upon more central cellular mechanisms that involve maintenance of mitochondrial membrane permeability through Bcl-2 family members, trophic factors, and mitochondrial energy reserves. Conclusions: By targeting critical elements that determine neuronal and vascular survival during Alzheimer disease, successful development of clinical applications can emerge for the treatment of neurodegenerative disorders. Show more

Keywords: amyloid precursor protein, β-amyloid, β-catenin, cell cycle, glycogen synthase kinase, metabotropic glutamate receptor, mitochondria, phosphatidylserine, presenilin

Citation: Restorative Neurology and Neuroscience, vol. 22, no. 2, pp. 87-104, 2004

Authors: Genc, Sermin | Koroglu, Tolga F. | Genc, Kursad

Article Type: Research Article

Abstract: Purpose: To provide an overview of the current knowledge on neuroprotective properties of Erythropoietin (Epo), mechanisms by which Epo produces neuroprotection, and signaling pathways regulated by Epo in the nervous system. Methods: The Medline database was searched for articles on the neuroprotective properties of Epo. Experimental and clinical studies were systematically reviewed. Results: In addition to promoting the survival, proliferation, and differentiation of immature erythroid cells, Epo and the Epo receptor (EpoR) …have recently been shown to exist and function in the nervous system. The Epo/EpoR system plays a critical role in neurodevelopment and neuroprotection. Epo ameliorates or prevents neuronal injury by neuroprotective, anti-apoptotic, anti-inflammatory, anti-oxidant, angiogenic, neurogenic and neurotrophic effects in cell culture and animal models of neurological diseases. The clinical effectiveness of recombinant human Epo in ischemic stroke in human patients has also been reported recently. Conclusion: Recent studies suggest that Epo is a potential novel neurotherapeutic agent and further clinical studies are warranted. Show more

Keywords: erythropoietin, neuroprotection, neurodegeneration, apoptosis, signaling pathways, neuroinflammation

Citation: Restorative Neurology and Neuroscience, vol. 22, no. 2, pp. 105-119, 2004

Authors: Marini, Ann M. | Jiang, Xueying | Wu, Xuan | Tian, Feng | Zhu, Daming | Okagaki, Peter | Lipsky, Robert H.

Article Type: Research Article

Abstract: Purpose: Brain-derived neurotrophic factor (BDNF) is a member of the family of neurotrophins and promotes diverse effects in neurons including development, maintenance of function, synaptic plasticity, and survival in different animal models. We present advances in our understanding of the genomics of the BDNF gene (bdnf) and its regulation by calcium-activated transcription factors, including cAMP response element binding protein (CREB) and more recently, nuclear factor kappaB (NF-κB) and discuss these findings in …the context of neuronal plasticity and survival. Methods: We used amplified bdnf complementary DNAs (cDNAs) and genomic DNA templates for direct sequencing and sequence variant discovery, information mining of public databases, and conventional molecular and cellular biology approaches to screen bdnf for novel regulatory elements, alternatively spliced exons, and functional sequence variants. Results: We discovered a candidate NF-κB site in promoter 3 of bdnf and showned that activation of N-methyl-D-aspartate (NMDA) inotropic glutamate receptors increased bdnf expression through an NF-κB-dependent pathway and extended the finding to show that NF-κB was required for NMDA neuroprotection in vitro. In addition, sequence analysis of bdnf cDNAs from different brain regions predicted at least three pre-pro-BDNF protein isoforms, two of which were previously unknown. Each isoform differs at the amino terminus and may have functional importance. Conclusions: Given the central role that BDNF plays in the developing and adult nervous system, understanding how BDNF is regulated and how it functions will enhance our knowledge of its diverse effects, which may lead to more effective treatments for neurodegenerative disorders and reveal the role of BDNF in complex phenotypes related to behavior. Show more

Citation: Restorative Neurology and Neuroscience, vol. 22, no. 2, pp. 121-130, 2004

Authors: Heese, Klaus | Inoue, Noriko | Nagai, Yasuo | Sawada, Tohru

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is one of the most common and challenging neurodegenerative diseases in humans and is characterized by: progressive impairment in cognitive function, degeneration of cholinergic neurons of the basal forebrain (CBF), neurofibrillary tangles and amyloid beta-peptide (Aβ) depositions. The amyloid precursor protein (APP) is a transmembrane protein of which abnormal processing produces Aβ that is associated with the pathogenesis of AD. Neurotrophic factors have attracted much attention for their potential …as a remedy for neurological disorders. In this regard, nerve growth factor (NGF) has generated a great interest as a potential target for the treatment of AD. This interest is based on the observation that CBF neurons, which provide the major source of cholinergic innervation to the cerebral cortex and hippocampus, undergo selective and severe degeneration in advanced AD and that the survival of CBF neurons depends upon NGF and its receptors, namely, trkA and p75NTR. This review focuses on recent findings about APP, NGF and their potential signaling-connections to the protein encoded by the 'Sunday-driver' (SYD) gene. Show more

Citation: Restorative Neurology and Neuroscience, vol. 22, no. 2, pp. 131-136, 2004