Temporal profile and cell subtype distribution of activated caspase-3 following experimental traumatic brain injury
Temporal profile and cell subtype distribution of activated caspase-3 following experimental traumatic brain injury
复制标题
DOI：
10.1046/j.1471-4159.2000.0751264.x
复制
发表时间：
2000-09-01
影响因子：
4.7
通讯作者：
Kampfl, A
中科院分区：
文献类型：
--
作者：
Beer, R;Franz, G;Kampfl, A
本研究探讨了大鼠皮层撞击伤后活化的caspase-3的表达和细胞亚型分布。在损伤后6 h至14 d的时间间隔内，处死动物并检测caspase-3蛋白水解活性亚基p18的蛋白表达。此外，我们还研究了caspase-3激活对细胞骨架蛋白α-血影蛋白的蛋白水解的影响。p18和caspase-3特异性120-kDa分解产物α-血影蛋白的蛋白水平增加被认为是在皮质同侧损伤部位从创伤后6至72小时。免疫组织化学检查显示，p18在神经元，星形胶质细胞和少突胶质细胞的表达增加，从6至72小时后的冲击损伤，相比之下，没有证据表明，在小胶质细胞中的caspase-3激活在所有的时间点调查。caspase-3阳性细胞的定量分析显示，caspase-3阳性神经元的数量超过caspase-3阳性胶质细胞的数量，从6至72小时的损伤。此外，核组织病理学使用苏木精鉴定的p18-免疫阳性细胞的同时评估，表现出类似于在损伤部位的同侧皮质的形态轮廓。相比之下，没有证据表明增加p18的表达或α-血影蛋白的蛋白水解被视为在同侧海马，对侧皮质，或海马后的影响长达14天。我们的研究结果是第一次证明在大鼠创伤性脑损伤后不同的中枢神经系统细胞中激活的caspase-3的同时表达。我们的研究结果还表明，在体内实验性TBI后，激活的caspase-3在神经元和胶质细胞凋亡变性中起着重要作用。
This study investigated the temporal expression and cell subtype distribution of activated caspase-3 following cortical impact-induced traumatic brain injury in rats. The animals were killed and examined for protein expression of the proteolytically active subunit of caspase-3, p18, at intervals from 6 h to 14 days after injury. In addition, we also investigated the effect of caspase-3 activation on proteolysis of the cytoskeletal protein alpha-spectrin. Increased protein levels of p18 and the caspase-3-specific 120-kDa breakdown product to alpha-spectrin were seen in the cortex ipsilateral to the injury site from 6 to 72 h after the trauma. Immunohistological examinations revealed increased expression of p18 in neurons, astrocytes, and oligodendrocytes from 6 to 72 h following impact injury, In contrast, no evidence of caspase-3 activation was seen in microglia at all time points investigated. Quantitative analysis of caspase-3-positive cells revealed that the number of caspase-3-positive neurons exceeded the number of caspase-3-positive glia cells from 6 to 72 h after injury. Moreover, concurrent assessment of nuclear histopathology using hematoxylin identified p18-immunopositive cells exhibiting apoptotic-like morphological profiles in the cortex ipsilateral to the injury site. In contrast, no evidence of increased p18 expression or alpha-spectrin proteolysis was seen in the ipsilateral hippocampus, contralateral cortex, or hippocampus up to 14 days after the impact. Our results are the first to demonstrate the concurrent expression of activated caspase-3 in different CNS cells after traumatic brain injury in the rat. Our findings also suggest a contributory role of activated caspase-3 in neuronal and glial apoptotic degeneration after experimental TBI in vivo.