Electrical Stimulation of the Cerebral Cortex Exerts Antiapoptotic, Angiogenic, and Anti-Inflammatory Effects in Ischemic Stroke Rats Through Phosphoinositide 3-Kinase/Akt Signaling Pathway
Electrical Stimulation of the Cerebral Cortex Exerts Antiapoptotic, Angiogenic, and Anti-Inflammatory Effects in Ischemic Stroke Rats Through Phosphoinositide 3-Kinase/Akt Signaling Pathway
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DOI：
10.1161/strokeaha.109.563627
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发表时间：
2009-11-01
期刊：
影响因子：
8.3
通讯作者：
Date, Isao
中科院分区：
文献类型：
--
作者：
Baba, Tanefumi;Kameda, Masahiro;Date, Isao
背景和目的--电刺激对缺血性中风的神经保护作用最近已被证实，但其潜在的机制仍然知之甚少。方法--成年Wistar大鼠，体重200 - 250克，接受右侧大脑中动脉闭塞90分钟。再灌注后1h，将电极植入大鼠右额硬膜外腔。电刺激，在预设的电流（0至200 μ A）和频率（0至50 Hz），进行了1周。中风动物在大脑中动脉后3天和1周进行行为测试，然后立即安乐死进行蛋白质和免疫组织化学测定。在证实了行为学和组织学的益处后，随后的实验追求了电刺激通过磷酸肌醇3-激酶依赖性途径发挥抗凋亡作用的机制假说;因此，在本发明中，在存在或不存在磷酸肌醇3-激酶的特异性抑制剂的情况下进行皮层刺激结果-皮层刺激通过激活抗凋亡级联反应消除了损伤皮层中缺血相关的凋亡细胞增加，磷酸肌醇3-激酶抑制剂LY 294002可逆转该作用，这在行为学和生物化学上都有反映。此外，脑神经营养因子（胶质细胞源性神经营养因子，脑源性神经营养因子，血管内皮生长因子）的水平上调，这与增强血管生成和抑制炎症细胞增殖在缺血cortic.Conclusions -这些结果表明，电刺激通过磷酸肌醇3-激酶途径防止细胞凋亡。因此，缺血性脑可能已被呈现为一个滋养微环境，其特征在于强大的血管生成和减少的小胶质细胞/星形胶质细胞增殖，导致梗死体积减少和行为恢复。电刺激是治疗脑缺血的一种新的有效手段。（中风。2009; 40：e598-e605）。
Background and Purpose - Neuroprotective effects of electric stimulation have been recently shown in ischemic stroke, but the underlying mechanisms remain poorly understood.Methods - Adult Wistar rats weighing 200 to 250 g received occlusion of the right middle cerebral artery for 90 minutes. At 1 hour after reperfusion, electrodes were implanted to rats on the right frontal epidural space. Electric stimulation, at preset current (0 to 200 mu A) and frequency (0 to 50 Hz), was performed for 1 week. Stroke animals were subjected to behavioral tests at 3 days and 1 week postmiddle cerebral artery and then immediately euthanized for protein and immunohistochemical assays. After demonstration of behavioral and histological benefits, subsequent experiments pursued the mechanistic hypothesis that electric stimulation exerted antiapoptotic effects through the phosphoinositide 3-kinase-dependent pathway; thus, cortical stimulation was performed in the presence or absence of specific inhibitors of phosphoinositide 3-kinase (LY294002) in stroke rats.Results - Cortical stimulation abrogated the ischemia-associated increase in apoptotic cells in the injured cortex by activating antiapoptotic cascades, which was reversed by the phosphoinositide 3-kinase inhibitor LY294002 as reflected behaviorally and immunohistochemically. Furthermore, brain levels of neurotrophic factors (glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor, vascular endothelial growth factor) were upregulated, which coincided with enhanced angiogenesis and suppressed proliferation of inflammatory cells in the ischemic cortex.Conclusions - These results suggest that electric stimulation prevents apoptosis through the phosphoinositide 3-kinase pathway. Consequently, the ischemic brain might have been rendered as a nurturing microenvironment characterized by robust angiogenesis and diminished microglial/astrocytic proliferation, resulting in the reduction of infarct volumes and behavioral recovery. Electric stimulation is a novel and potent therapeutic tool for cerebral ischemia. (Stroke. 2009; 40: e598-e605.)