McIntosh T K, Saatman K E, Raghupathi R, Graham D I, Smith D H, Lee V M, Trojanowski J Q
Department of Neurosurgery, University of Pennsylvania, Philadelphia, USA.
Neuropathol Appl Neurobiol. 1998 Aug;24(4):251-67. doi: 10.1046/j.1365-2990.1998.00121.x.
The mechanisms underlying secondary or delayed cell death following traumatic brain injury (TBI) are poorly understood. Recent evidence from experimental models of TBI suggest that diffuse and widespread neuronal damage and loss is progressive and prolonged for months to years after the initial insult in selectively vulnerable regions of the cortex, hippocampus, thalamus, striatum, and subcortical nuclei. The development of new neuropathological and molecular techniques has generated new insights into the cellular and molecular sequelae of brain trauma. This paper will review the literature suggesting that alterations in intracellular calcium with resulting changes in gene expression, activation of reactive oxygen species (ROS), activation of intracellular proteases (calpains), expression of neurotrophic factors, and activation of cell death genes (apoptosis) may play a role in mediating delayed cell death after trauma. Recent data suggesting that TBI should be considered as both an inflammatory and/or a neurodegenerative disease is also presented. Further research concerning the complex molecular and neuropathological cascades following brain trauma should be conducted, as novel therapeutic strategies continue to be developed.
创伤性脑损伤（TBI）后继发性或延迟性细胞死亡的潜在机制尚不清楚。TBI实验模型的最新证据表明，在最初损伤后的数月至数年里，在皮质、海马体、丘脑、纹状体和皮质下核等选择性易损区域，弥漫性和广泛性的神经元损伤和丢失是渐进性且持续时间较长的。新的神经病理学和分子技术的发展为脑外伤的细胞和分子后遗症带来了新的见解。本文将综述相关文献，这些文献表明细胞内钙的改变以及随之而来的基因表达变化、活性氧（ROS）的激活、细胞内蛋白酶（钙蛋白酶）的激活、神经营养因子的表达以及细胞死亡基因（凋亡）的激活可能在介导创伤后延迟性细胞死亡中发挥作用。还介绍了近期表明TBI应被视为炎症性和/或神经退行性疾病的数据。随着新的治疗策略不断被开发，应针对脑外伤后复杂的分子和神经病理学级联反应开展进一步研究。
