Review of current evidence for apoptosis after spinal cord injury
Review of current evidence for apoptosis after spinal cord injury
复制标题
DOI：
10.1089/neu.2000.17.915
复制
发表时间：
2000-10-01
影响因子：
4.2
通讯作者：
Bresnahan, JC
中科院分区：
文献类型：
--
作者：
Beattie, MS;Farooqui, AA;Bresnahan, JC
脊髓损伤 (SCI) 最初发生机械性组织破坏，随后是一段时间的继发性损伤，导致病变面积增大。长期以来，人们一直认为继发性损伤是由于细胞坏死（或被动）死亡而导致的细胞破坏的持续。最近来自脑损伤和缺血的证据表明，细胞凋亡（一种在发育过程中出现的程序性细胞死亡的活跃形式）可能在成年期中枢神经系统损伤中发挥作用。在这里，我们回顾了细胞凋亡在 SCI 病理生理学中可能重要的证据。目前，许多实验室提供了强有力的形态学和生化证据，证明 SCI 后存在细胞凋亡。细胞凋亡发生在神经元、少突胶质细胞、小胶质细胞，或许还有星形胶质细胞中。白质束中少突胶质细胞的死亡在损伤后持续数周，并可能导致损伤后脱髓鞘。 SCI后细胞凋亡的介质尚不清楚，但小胶质细胞和死亡少突胶质细胞之间存在密切关系，表明小胶质细胞活化可能参与其中。还有证据表明，已知参与其他细胞和系统凋亡的重要细胞内途径被激活。例如，半胱氨酸蛋白酶半胱天冬酶家族的一些成员在 SCI 后被激活。 SCI 后病变的演变似乎涉及坏死和细胞凋亡。对 SCI 后细胞凋亡的更好理解可能会带来新的治疗干预策略，从而减少继发性损伤。
The initial mechanical tissue disruption of spinal cord injury (SCI) is followed by a period of secondary injury that increases the size of the lesion. The secondary injury has long been thought to be due to the continuation of cellular destruction through necrotic (or passive) cell death. Recent evidence from brain injury and ischemia suggested that cellular apoptosis, an active form of programmed cell death seen during development, could play a role in CNS injury in adulthood. Here, we review the evidence that apoptosis may be important in the pathophysiology of SCI. There is now strong morphological and biochemical evidence from a number of laboratories demonstrating the presence of apoptosis after SCI. Apoptosis occurs in populations of neurons, oligodendrocytes, microglia, and, perhaps, astrocytes. The death of oligodendrocytes in white matter tracts continues for many weeks after injury and may contribute to post-injury demyelination. The mediators of apoptosis after SCI are not well understood, but there is a close relationship between microglia and dying oligodendrocytes, suggesting that microglial activation may be involved. There is also evidence for the activation of important intracellular pathways known to be involved in apoptosis in other cells and systems. For example, some members of the caspase family of cysteine proteases are activated after SCI. It appears that the evolution of the lesion after SCI involves both necrosis and apoptosis. It is likely that better understanding of apoptosis after SCI will lead to novel strategies for therapeutic interventions that can diminish secondary injury.