Journal of neuropathology and experimental neurology
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J. Neuropathol. Exp. Neurol. · Mar 2005
ReviewRecent advances in hereditary spinocerebellar ataxias.
In recent years, molecular genetic research has unraveled a major part of the genetic background of autosomal dominant and recessive spinocerebellar ataxias. These advances have also allowed insight in (some of) the pathophysiologic pathways assumed to be involved in these diseases. For the clinician, the expanding number of genes and genetic loci in these diseases and the enormous clinical heterogeneity of specific ataxia subtypes complicate management of ataxia patients. In this review, the clinical and neuropathologic features of the recently identified spinocerebellar ataxias are described, and the various molecular mechanisms that have been demonstrated to be involved in these disorders are discussed.
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J. Neuropathol. Exp. Neurol. · Aug 2003
ReviewFrom cell death to neuronal regeneration: building a new brain after traumatic brain injury.
During the past decade, there has been accumulating evidence of the involvement of passive and active cell death mechanisms in both the clinical setting and in experimental models of traumatic brain injury (TBI). Traditionally, research for a treatment of TBI consists of strategies to prevent cell death using acute pharmacological therapy. However, to date, encouraging experimental work has not been translated into successful clinical trials. ⋯ Recent experimental studies have identified a variety of candidate cell lines for transplantation into the injured CNS. Additionally, the characterization of the neurogenic potential of specific regions of the adult mammalian brain and the elucidation of the molecular controls underlying regeneration may allow for the development of neuronal replacement therapies that do not require transplantation of exogenous cells. These novel strategies may represent a new opportunity of great interest for delayed intervention in patients with TBI.
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Many of us who conduct research based on disorders that uniquely affect the human nervous system are involved directly or indirectly with brain banks. Brain banking is by its very nature a multi-disciplinary endeavor that requires close collaboration with our colleagues in clinical departments and also with the families and patients who are donors of brain tissue. These brain tissues will ultimately be used for many types of basic science investigations. ⋯ This paper represents a broad overview of brain banking and the issues that are common to all brain banks. Legal and ethical concerns regarding confidentiality of donor records and donor recruitment procedures, as well as safety precautions for technical staff, tissue banking methods and disbursement will be discussed. Finally, issues surrounding financial support for brain banks will be considered.
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J. Neuropathol. Exp. Neurol. · Apr 2003
ReviewSignaling of cell death and cell survival following focal cerebral ischemia: life and death struggle in the penumbra.
Focal ischemia by middle cerebral artery occlusion (MCAO) results in necrosis at the infarct core and activation of complex signal pathways for cell death and cell survival in the penumbra. Recent studies have shown activation of the extrinsic and intrinsic pathways of caspase-mediated cell death, as well as activation of the caspase-independent signaling pathway of apoptosis in several paradigms of focal cerebral ischemia by transient MCAO to adult rats and mice. The extrinsic pathway (cell-death receptor pathway) is initiated by activation of the Fas receptor after binding to the Fas ligand (Fas-L); increased Fas and Fas-L expression has been shown following focal ischemia. ⋯ Recent studies have shown the mitochondrial release of other factors; Smac/DIABLO (Smac: second mitochondrial activator of caspases: DIABLO: direct IAP binding protein with low pI) binds to and neutralizes the effects of the X-linked inhibitor of apoptosis (XIAP). Finally, apoptosis-inducing factor (AIF) translocates to the mitochondria and the nucleus following focal ischemia and produces peripheral chromatin condensation and large-scale DNA strands, thus leading to the caspase-independent cell death pathway of apoptosis. Delineation of the pro-apoptotic and pro-survival signals in the penumbra may not only increase understanding of the process but also help to rationalize strategies geared to reducing brain damage targeted at the periphery of the infarct core.