Preconditioning prevents ischemia-induced neuronal death through persistent Akt activation in the penumbra region of the rat brain
Preconditioning prevents ischemia-induced neuronal death through persistent Akt activation in the penumbra region of the rat brain
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DOI：
10.1292/jvms.66.521
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发表时间：
2004-05-01
影响因子：
1.2
通讯作者：
Kawahara, K
中科院分区：
文献类型：
--
作者：
Nakajima, T;Iwabuchi, S;Kawahara, K
短暂的缺血，即大脑中动脉区域的预处理，诱导缺血耐受，减少由随后的致死性缺血引起的脑梗死体积。然而，人们对这种现象背后的分子机制知之甚少。在本研究中，我们研究了Akt（一种丝氨酸/苏氨酸激酶）的激活在脑缺血耐受中的作用。Western blot分析显示，缺血1小时后，非预处理组和预处理组的Akt均被激活，但预处理组的激活持续时间较长。免疫组化分析表明，预处理诱导的预防作用的快速下降的Akt的激活水平是由于持续激活的Akt在半影区。此外，TUNEL染色表明，预处理抑制神经元死亡的增加，可能通过在半影区的细胞凋亡，以防止梗死的蔓延。由于Akt的激活已被报道可以保护细胞免受应激，因此本研究结果表明，预处理诱导的半暗带区Akt的持续激活在脑缺血耐受中起重要作用。
A brief period of ischemia, i.e. preconditioning of the middle cerebral artery territory, induces ischemic tolerance reducing the cerebral infarction volume caused by subsequent lethal ischemia. Nevertheless, little is known about the molecular mechanisms underlying this phenomenon. In the present study, we examined the involvement of the activation of Akt, a serine/threonine kinase, in the cerebral ischemic tolerance. Western blot analysis showed that Akt was activated in both non-preconditioned and preconditioned groups after ischemia for I hr, but the activation was long-lasting in the preconditioned rats. Immunohistochemical analysis demonstrated that the preconditioning-induced preventive effect on a rapid decrease in the activation level of Akt was due to the persistent activation of Akt in the penumbra region. In addition, TUNEL staining demonstrated that the preconditioning treatment inhibited the augmentation of neuronal death probably through apoptosis in the penumbra region to prevent the spread of infarction. Since the activation of Akt has been reported to protect cells from stress, the present results suggest that the preconditioning-induced persistent activation of Akt in the penumbra region plays an important role in ischemic tolerance of the brain.