Neuronal damage and plasticity identified by microtubule-associated protein 2, growth-associated protein 43, and cyclin D1 immunoreactivity after focal cerebral ischemia in rats
Neuronal damage and plasticity identified by microtubule-associated protein 2, growth-associated protein 43, and cyclin D1 immunoreactivity after focal cerebral ischemia in rats
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DOI：
10.1161/01.str.29.9.1972
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发表时间：
1998-09-01
期刊：
影响因子：
8.3
通讯作者：
Chopp, M
中科院分区：
文献类型：
--
作者：
Li, Y;Jiang, N;Chopp, M
背景和目的--脑缺血后治疗干预的一个目标是促进改善功能结果。预后的改善可能与脑梗塞体积的减少和大脑可塑性的提高有关。在发育中的大脑中，神经元的生长伴随着特定蛋白的表达，包括微管相关蛋白2(MAP-2)、生长相关蛋白43(GAP-43)和细胞周期蛋白D1。在本研究中，我们检测了大鼠局灶性脑缺血后突起损伤和可塑性相关蛋白(MAP-2和GAP-43)的表达以及细胞周期(Cyclin D1)的表达。方法28只大鼠大脑中动脉闭塞2小时，再灌注6小时、12小时、2天、7天、14天、21天和28天(每个时间点4天)，对照组(3只)和正常大鼠(2只)进行免疫组织化学染色，检测MAP-2、GAP-43和Cyclin D1抗体。结果：MAP-2和GAP-43在大部分受损神经元中均失去免疫反应性。相反，在再灌流早期(如6h)位于缺血中心的形态完整或改变的神经元，以及在较长时间再灌流后位于缺血中心(半影区)的神经元中，MAP-2、GAP-43和细胞周期蛋白D1的选择性增加。结论：短暂性局灶性脑缺血后，神经元结构蛋白(树突中的MAP-2和轴突中的GAP-43)和细胞周期蛋白Cyclin D1的选择性表达提示了缺血损伤神经元的代偿和修复机制。
Background and Purpose-An objective of therapeutic intervention after cerebral ischemia is to promote improved functional outcome. Improved outcome may be associated with a reduction of the volume of cerebral infarction and the promotion of cerebral plasticity. In the developing brain, neuronal growth is concomitant with expression of particular proteins, including microtubule-associated protein 2 (MAP-2), growth-associated protein 43 (GAP-43), and cyclin D1. In the present study we measured the expression of select proteins associated with neurite damage and plasticity (MAP-2 and GAP-43) as well as cell cycle (cyclin D1) after induction of focal cerebral ischemia in the rat.Methods-Brains from rats (n=28) subjected to 2 hours of middle cerebral artery occlusion and 6 hours, 12 hours, and 2, 7, 14, 21, and 28 days (n=4 per time point) of reperfusion and control sham-operated (n=3) and normal (n=2) rats were processed by immunohistochemistry with antibodies raised against MAP-2, GAP-43, and cyclin D1. Double staining of these proteins for cellular colocalization was also performed.Results-Loss of immunoreactivity of both MAP-2 and GAP-43 was observed in most damaged neurons in the ischemic core. In contrast, MAP-2, GAP-43, and cyclin D1 were selectively increased in morphologically intact or altered neurons localized to the ischemic core at an early stage (eg, 6 hours) of reperfusion and in the boundary zone to the ischemic core (penumbra) during longer reperfusion times.Conclusions-The selective expressions of the neuronal structural proteins (MAP-2 in dendrites and GAP-43 in axons) and the cyclin D1 cell cycle protein in neurons observed in the boundary zone to the ischemic core are suggestive of compensatory and repair mechanisms in ischemia-damaged neurons after transient focal cerebral ischemia.