Cellular and molecular events underlying the dysregulated response of the aged brain to stroke: A mini-review
Cellular and molecular events underlying the dysregulated response of the aged brain to stroke: A mini-review
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DOI：
10.1159/000112845
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发表时间：
2008-01-01
期刊：
影响因子：
3.5
通讯作者：
Popa-Wagner, Aurel
中科院分区：
文献类型：
--
作者：
Petcu, Eugen Bogdan;Sfredel, Veronica;Popa-Wagner, Aurel
背景：与年龄相关的脑损伤，包括中风，是导致身体和精神残疾的主要原因。目的：因此，研究老年受试者脑卒中后功能恢复的基本机制具有相当大的临床意义。方法：这篇综述总结了年龄对动物模型中风后恢复的影响，重点是潜在的细胞机制。结果：我们实验室和其他地方的数据表明，在行为上，老年大鼠比年轻大鼠因中风而受到更严重的损害，而且它们的功能恢复也有所减弱。年轻和老年动物的梗塞体积没有显着差异，但对中风的细胞学反应存在明显差异，最显着的是与年龄相关的神经胶质疤痕发展的加速。老年大鼠的早期梗塞与 BrdU 阳性小胶质细胞和星形胶质细胞过早积累、活化少突胶质细胞持续存在、神经元变性发生率高和细胞凋亡加速有关。在老年大鼠中，神经上皮阳性细胞迅速融入神经胶质疤痕中，但这些神经上皮样细胞对年轻或老年动物梗死皮层的神经发生没有做出显着贡献。老年大鼠中 MAP1B 等可塑性相关蛋白的反应延迟。中风后 2 周，β-淀粉样前体蛋白 (A-β) 的神经毒性 C 末端片段数量与年龄相关，进一步延迟了组织恢复。结论：现有证据表明，老年大脑有能力对损伤产生细胞增殖反应，但老年动物对脑损伤的细胞和遗传反应的时间失调，从而进一步损害功能恢复。阐明衰老大脑中这种现象的分子基础可能会产生老年人神经恢复的新方法。版权所有 (C) 2007 S. Karger AG，巴塞尔。
Background: Age-related brain injuries, including stroke, are a major cause of physical and mental disabilities. Objective: Therefore, studying the basic mechanism underlying functional recovery after brain stroke in aged subjects is of considerable clinical interest. Methods: This review summarizes the effects of age on recovery after stroke in an animal model, with emphasis on the underlying cellular mechanisms. Results: Data from our laboratory and elsewhere indicate that, behaviorally, aged rats were more severely impaired by stroke than young rats, and they also showed diminished functional recovery. Infarct volume did not differ significantly between young and aged animals, but critical differences were apparent in the cytological response to stroke, most notably an age-related acceleration in the development of the glial scar. Early infarct in older rats is associated with premature accumulation of BrdU-positive microglia and astrocytes, persistence of activated oligodendrocytes, a high incidence of neuronal degeneration and accelerated apoptosis. In aged rats, neuroepithelial-positive cells were rapidly incorporated into the glial scar, but these neuroepithelial-like cells did not make a significant contribution to neurogenesis in the infarcted cortex in young or aged animals. The response of plasticity-associated proteins like MAP1B, was delayed in aged rats. Tissue recovery was further delayed by an age-related increase in the amount of the neurotoxic C-terminal fragment of the beta-amyloid precursor protein (A-beta) at 2 weeks poststroke. Conclusion: The available evidence indicates that the aged brain has the capability to mount a cytoproliferative response to injury, but the timing of the cellular and genetic response to cerebral insult is dysregulated in aged animals, thereby further compromising functional recovery. Elucidating the molecular basis for this phenomenon in the aging brain could yield novel approaches to neurorestoration in the elderly. Copyright (C) 2007 S. Karger AG, Basel.