Reactive microglia in cerebral ischaemia: an early mediator of tissue damage?
Reactive microglia in cerebral ischaemia: an early mediator of tissue damage?
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脑缺血中的反应性小胶质细胞：组织损伤的早期介质？
DOI：
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发表时间：
1995
影响因子：
5
通讯作者：
G. Kreutzberg
中科院分区：
文献类型：
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作者：
J. Gehrmann;R. Banati;C. Wiessnert;K. Hossmann;G. Kreutzberg
小胶质细胞活化是脑缺血后迅速发生的细胞反应。小胶质细胞增殖，被募集到病变部位，调节几种表面分子的表达，包括主要组织相容性复合物I类和II类抗原、补体受体和淀粉样前体蛋白（APP）以及新表达的细胞因子，如白细胞介素-1和转化生长因子β 1。缺血诱导的APP产生可能有助于在低融合条件下老年脑中的淀粉样蛋白沉积。在超微结构上，小胶质细胞转化为吞噬细胞，清除坏死的神经元，但即使在坏死神经元附近，仍然尊重最终存活神经元的完整性。小胶质细胞活化在缺血后几分钟内开始，因此先于形态学上可检测的神经元损伤。它还涉及缺血后前24小时内的一过性全身反应，即使在最终没有神经元细胞死亡的部位也是如此。在功能方面，小胶质细胞反应似乎是缺血的双刃剑。活化的小胶质细胞可通过释放活性氧、一氧化氮、蛋白酶或炎性细胞因子发挥细胞毒性效应子功能。所有这些细胞毒性化合物可引起缺血后的旁观者损伤。缺血后小胶质细胞活化的药理学抑制相应地减弱了细胞死亡和组织损伤的程度。然而，活化的小胶质细胞通过分泌诸如转化生长因子β 1的因子来支持组织修复，转化生长因子β 1可以限制组织损伤以及抑制星形胶质细胞瘢痕形成。与超微结构观察结果一致，缺血时小胶质细胞活化是一种严格控制的事件。通过分泌细胞因子和生长因子，活化的小胶质细胞最有可能在缺血中起到看似相反的功能，即维持以及去除受损的神经元。在导致神经元坏死的事件级联中，缺血后小胶质细胞干预的药理学调节可能有助于改善CNS缺血后的结构和功能结局。
Microglial cell activation is a rapidly occurring cellular response to cerebral ischaemia. Microglia proliferate, are recruited to the site of lesion, npregulate the expression of several surface molecules including major histocom‐patibility complex class I and II antigens, complement receptor and the amyloid precursor protein (APP) as well as newly expressed cytokines, e.g. interleukin‐1 and transforming growth factor pl. The ischaemia‐induced production of APP may contribute to amyloid deposition in the aged brain under conditions of hypofusion. Ultra‐structurally, microglia transform into phagocytes removing necrotic neurons but still respecting the integrity of eventually surviving neurons even in the close vicinity of necrotic neurons. Microglial activation starts within a few minutes after ischaemia and thus precedes the morphologically detectable neuronal damage. It additionally involves a transient generalized response within the first 24 hours post‐ischaemia even at sites without eventual neuronal cell death. In functional terms, the microglial reaction appears to be a double‐edged sword in ischaemia. Activated microglia may exert a cytotoxic effector function by releasing reactive oxygen species, nitric oxide, proteinases or inflammatory cytokines. All of these cytotoxic compounds may cause bystander damage following ischaemia. Pharmacological suppression of microglial activation after ischaemia has accordingly attenuated the extent of cell death and tissue damage. However, activated microglia support tissue repair by secreting factors such as transforming growth factor βl which may limit tissue damage as well as suppress astroglial scar formation. In line with ultrastructural observations microglial activation in ischaemia is a strictly controlled event. By secreting cytokines and growth factors activated microglia most likely serve seemingly opposed functions in ischaemia, i.e. maintenance as well as removal of injured neurons. Post‐ischaemic pharmacological modulation of microglial intervention in the cascade of events that lead to neuronal necrosis may help to improve the structural and functional outcome following CNS ischaemia.
影响因子：
4.4
作者：
C. Chao;T. Molitor;Shuxian Hu
通讯作者：
C. Chao;T. Molitor;Shuxian Hu
影响因子：
4.4
作者：
M. Racke;S. Dhib-Jalbut;B. Cannella;P. Albert;C. Raine;D. McFarlin
通讯作者：
M. Racke;S. Dhib-Jalbut;B. Cannella;P. Albert;C. Raine;D. McFarlin