Temporal and spatial profile of bid cleavage after experimental traumatic brain injury
Temporal and spatial profile of bid cleavage after experimental traumatic brain injury
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DOI：
10.1097/00004647-200208000-00006
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发表时间：
2002-08-01
影响因子：
6.3
通讯作者：
Kampfl, A
中科院分区：
文献类型：
--
作者：
Franz, G;Beer, R;Kampfl, A
细胞凋亡在创伤性脑损伤后CNS细胞变性的级联反应中起重要作用。但是，其潜在机制尚不清楚，作者研究了大鼠皮质撞击损伤后6小时至7天促凋亡蛋白Bid的时间分布和细胞亚型分布。创伤后6小时至3天，在损伤部位同侧皮质中观察到tBid蛋白水平增加。免疫组织学检查显示，tBid的表达在神经元，星形胶质细胞和少突胶质细胞从6小时到3天后的冲击损伤，并同时评估DNA损伤使用TUNEL鉴定tBid免疫阳性细胞的创伤皮质中的tBid样形态。此外，半胱天冬酶-8和半胱天冬酶-9的Bid裂解和活化发生在相似的时间点，并且在相似的脑区域（即，皮质层2至5）。与此相反，有没有证据表明caspase-8或caspase-9加工或Bid裂解在同侧海马，对侧皮质，海马损伤后7天。结果提供了体内实验性创伤性脑损伤后创伤皮层中Bid裂解的第一个证据，并证明tBid在神经元和神经胶质细胞中表达。此外，研究结果表明Bid的裂解可能与引发剂caspase-8和caspase-9的活化有关。最后，这些数据支持这一假设，即Bid的裂解有助于不同的CNS细胞在受损的皮层的凋亡变性。
Apoptosis plays an essential role in the cascade of CNS cell degeneration after traumatic brain injury. However., the underlying mechanisms are poorly understood, The authors examined the temporal profile and cell subtype distribution of the proapoptotic protein Bid from 6 hours to 7 days after cortical impact injury in the rat. Increased protein levels of tBid were seen in the cortex ipsilateral to the injury site from 6 hours to 3 days after trauma. Immunohistologic examinations revealed expression of tBid in neurons, astrocytes, and oligodendrocytes from 6 hours to 3 days after impact injury, and concurrent assessment of DNA damage using TUNEL identified tBid-immunopositive cells with apoptoticlike morphology in the traumatized cortex. Moreover, Bid cleavage and activation of caspase-8 and caspase-9 occurred at similar time points, and in similar brain regions (i.e., cortical layers 2 to 5) after impact injury. In contrast, there was no evidence of caspase-8 or caspase-9 processing or Bid cleavage in the ipsilateral hippocampus, contralateral cortex, and hippocampus up to 7 days after the injury. The results provide the first evidence of Bid cleavage in the traumatized cortex after experimental traumatic brain injury in vivo, and demonstrate that tBid is expressed in neurons and glial cells. Further, findings indicate that cleavage of Bid may be associated with the activation of the initiator caspase-8 and caspase-9. Finally, these data support the hypothesis that cleavage of Bid contributes to the apoptotic degeneration of different CNS cells in the injured cortex.