Pathophysiology of Brain Ischemia: Penumbra, Gene Expression, and Future Therapeutic Options
| Autor: | B.J. Schaller, M. Bähr, M. Buchfelder |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Regulation of gene expression
Tetraspanins business.industry Penumbra Ischemia Excitotoxicity Gene Expression Membrane Proteins medicine.disease medicine.disease_cause Neuroprotection Brain Ischemia Brain ischemia Neurology Downregulation and upregulation Heat shock protein Humans Medicine Neurology (clinical) business Neuroscience |
| Zdroj: | European Neurology. 54:179-180 |
| ISSN: | 1421-9913 0014-3022 |
| DOI: | 10.1159/000090293 |
| Popis: | tors, and genes involved in RNA metabolism, infl ammation, and cell signaling [6] . All these studies suggest that there is a need to determine the time course of expression of neuroregulatory, angiogenic and apoptotic factors and their associated enzymes after ischemic stroke in humans underscoring the enormous complexity of ischemic biology and direct attention to potentially novel mechanisms for future exploration [6] . Such detailed analyses may allow for the design of new ‘neuroprotective’ treatment strategies, based on the observed signaling cascades in affected neurons in the ischemic territory [7] . The study by Vikman and Edvinsson [5] substantially supports the interesting hypothesis of upregulation of G protein-coupled receptors to be triggered in part by changes in shear stress as an important mechanism in the process following human stroke hypothesizing that cerebral ischemia induces enhanced transcription of some G protein-coupled receptors specifi cally in the artery leading to the ischemic region. The upregulation of these receptors and activation of previously mentioned processes together could help to explain the disruption in blood fl ow seen after cerebral ischemia (resulting locally in both enhanced vasoconstriction and in hypertrophy of the smooth muscle cells), possibly involved in the penumbral zone expansion. When rigorously tested and independently validated, data from large-scale gene expression analyses The ischemic penumbra represents a specifi c tissue region surrounding the ischemic core that has been identifi ed from more than 48 h after stroke in patients, and that has intermediate perfusion, where cells depolarize intermittently [1] . Without treatment, the penumbra often progresses to infarction owing to the effects of ongoing excitotoxicity, spreading depolarization and postischemic infl ammation. Maintenance of perfusion pressure in this region and hence survival of neurons within this electrophysiologically dynamic area of tissue is critical for the minimization of long-term damage. Because of these factors, the penumbra clearly has a limited life span and appears to undergo irreversible damage within a few hours unless reperfusion is initiated and/or neuroprotective therapy administered. Sharp et al. [2] proposed the existence of multiple ‘molecular penumbras’ that represent zones within which differential patterns of gene expression are determined on the basis of differential perfusion levels. A number of studies have examined gene regulation after ischemic stroke in animal models and in humans, using cDNAprinted microarrays [3–5] , and have demonstrated deregulation of numerous novel genes. Some ischemia-hypoxia response genes were upregulated and some were downregulated; these consisted of immediate early genes, heat shock proteins, antioxidative enzymes, trophic facReceived: October 21, 2005 Accepted: November 18, 2005 Published online: December 13, 2005 |
| Databáze: | OpenAIRE |
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