Temporal characterisation of pro- and anti-apoptotic mechanisms following diffuse traumatic brain injury in rats
Temporal characterisation of pro- and anti-apoptotic mechanisms following diffuse traumatic brain injury in rats
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DOI：
10.1054/jocn.2002.1132
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发表时间：
2002-09-01
影响因子：
2
通讯作者：
Vink, R
中科院分区：
文献类型：
--
作者：
Cernak, I;Chapman, SM;Vink, R
很少有研究描述了导致严重弥漫性轴突损伤的脑损伤模型中的细胞凋亡特征。从临床的角度来看，这种表征是必不可少的，因为弥漫性轴索损伤是人类头部损伤的主要组成部分。因此，本研究检测了主动和前摄caspase-3，以及bcl-2家族的bax，bcl-2和bcl-x成员的表达，以确定大鼠创伤性脑损伤模型中细胞凋亡的时间分布，该模型产生显著的弥漫性轴索损伤。戊巴比妥麻醉的雄性Sprague-Dawley大鼠使用弥漫性创伤性脑损伤的2 m冲击加速模型受伤。损伤后，弥漫性创伤导致bax表达增加，随后诱导caspase-3。caspase-3的增加与抗凋亡bcl-2表达的增加同时发生。诱导caspase-3后，Bcl-x水平升高，并且bcl-x水平升高持续至5天观察期结束。caspase-3活性表达的增加与TUNEL阳性细胞的出现有关。这些细胞在不同的时间在不同的脑区域被检测到，一些区域直到损伤后3天才显示出凋亡细胞。伤后7、14天未见TUNEL阳性细胞。DNA电泳证实，DNA断裂在损伤后3天最大。活性caspase-3水平的增加也与bcl-2水平的增加显著相关（r=0.80; P < 0.001），这表明弥漫性创伤性脑损伤后的凋亡级联反应是一种小心控制的细胞稳态反应。这种平衡的药理学操作可能提供一种治疗方法，用于预防细胞死亡和改善弥漫性创伤性脑损伤后的结果。(C)2002爱思唯尔科技有限公司。保留所有权利。
Few studies have characterised apoptosis in a brain injury model that causes a significant degree of diffuse axonal injury. Such characterisation is essential from a clinical viewpoint since diffuse axonal injury is a major component of human head injury. The present study therefore, examines the expression of active and proactive caspase-3, and the bax, bcl-2 and bcl-x members of the bcl-2 family, to characterise the temporal profile of apoptosis in a model of traumatic brain injury in rats that produces significant diffuse axonal injury. Pentobarbital anaesthetised male Sprague-Dawley rats were injured using the 2 m impact-acceleration model of diffuse traumatic brain injury. After injury, diffuse trauma resulted in an increased bax expression followed by induction of caspase-3. The increase in caspase-3 was simultaneous with an increase in anti-apoptotic bcl-2 expression. Bcl-x levels were increased after induction of caspase-3 and the increased levels of bcl-x were sustained to the end of the 5-day observation period. Increased active caspase-3 expression was associated with the appearance of TUNEL positive cells. These cells were detected in different brain regions at different times, with some regions showing no apoptotic cells until 3 days after injury. No TUNEL positive cells were detected at 7 and 14 days after injury. DNA electrophoresis confirmed that DNA fragmentation was maximal at 3 days after injury. Increased active caspase-3 levels were also significantly correlated with increased bcl-2 levels (r=0.80; P < 0.001) suggesting that the apoptotic cascade after diffuse traumatic brain injury is a carefully controlled cellular homeostatic response. Pharmacological manipulation of this balance may offer a therapeutic approach for preventing cell death and improving outcome after diffuse traumatic brain injury. (C) 2002 Elsevier Science Ltd. All rights reserved.