Aghili-Mehrizi Sina, Williams Eric, Yan Sandra, Willman Matthew, Willman Jonathan, Lucke-Wold Brandon
Department of Neurosurgery, University of Florida, Gainesville, FL 32608, USA.
Diseases. 2022 May 23;10(2):30. doi: 10.3390/diseases10020030.
Traumatic central nervous system injury is a leading cause of neurological injury worldwide. While initial neuroresuscitative efforts are focused on ameliorating the effects of primary injury through patient stabilization, secondary injury in neurotrauma is a potential cause of cell death, oxidative stress, and neuroinflammation. These secondary injuries lack defined therapy. The major causes of secondary injury in neurotrauma include endoplasmic reticular stress, mitochondrial dysfunction, and the buildup of reactive oxygen or nitrogenous species. Stress to the endoplasmic reticulum in neurotrauma results in the overactivation of the unfolded protein response with subsequent cell apoptosis. Mitochondrial dysfunction can lead to the release of caspases and the buildup of reactive oxygen species; several characteristics make the central nervous system particularly susceptible to oxidative damage. Together, endoplasmic reticulum, mitochondrial, and oxidative stress can have detrimental consequences, beginning moments and lasting days to months after the primary injury. Understanding these causative pathways has led to the proposal of various potential treatment options.
创伤性中枢神经系统损伤是全球神经损伤的主要原因。虽然最初的神经复苏努力集中在通过稳定患者病情来减轻原发性损伤的影响，但神经创伤中的继发性损伤是细胞死亡、氧化应激和神经炎症的潜在原因。这些继发性损伤缺乏明确的治疗方法。神经创伤中继发性损伤的主要原因包括内质网应激、线粒体功能障碍以及活性氧或氮物种的积累。神经创伤中内质网的应激会导致未折叠蛋白反应过度激活，随后细胞凋亡。线粒体功能障碍可导致半胱天冬酶的释放和活性氧的积累；几个特征使中枢神经系统特别容易受到氧化损伤。内质网、线粒体和氧化应激共同作用，可能在原发性损伤后的数分钟至数月内产生有害后果。对这些致病途径的了解引发了各种潜在治疗方案的提出。
