创伤性脑损伤(TBI)是影响中枢神经系统(CNS)的最常见病理状况之一。与TBI相关的神经功能缺损是由复杂的致病机制引起的,包括谷氨酸兴奋性毒性。炎症,脱髓鞘,程序性细胞死亡,或水肿的发展。有助于中枢神经系统反应的关键组成部分,损害控制,TBI后的再生是神经胶质细胞对组织损伤的反应,他们的激活,肥大,和增殖发生,然后形成神经胶质疤痕.神经胶质瘢痕在受损组织中形成屏障,并有助于在损伤后的急性期保护CNS。然而,这个过程通过产生永久性疤痕来防止晚期/慢性期的组织完全恢复,显著影响大脑功能。各种胶质细胞类型参与瘢痕形成,但是这个过程主要归因于反应性星形胶质细胞和小胶质细胞,在几种脑部疾病中起重要作用。新技术,包括全基因组转录组学和表观基因组分析,和无偏见的蛋白质组学,表明星形胶质细胞和小胶质细胞代表具有不同基因组和功能特征的异源性细胞亚群,负责它们在神经变性中的作用,神经保护和再生。根据不同神经胶质亚群的代表,因此,TBI后的组织损伤以及再生过程或延迟的神经变性可能在附近或偏远地区或不同的大脑结构中有所不同。这篇综述总结了TBI是一个复杂的过程,其中产生的效果是严重的-,区域和时间依赖性,并由中枢神经系统损伤模型和探索区域与病变部位的距离决定。这里,我们还讨论了有关细胞间信号的发现,TBI的长期影响和新型治疗方法的可能性。我们认为,一项以神经胶质细胞为重点的综合研究,参与组织损伤后过程,可能有助于TBI的进一步研究,并成为选择TBI模型的决定性因素。
Traumatic brain injury (TBI) is one of the most common pathological conditions impacting the central nervous system (CNS). A neurological deficit associated with TBI results from a complex of pathogenetic mechanisms including glutamate excitotoxicity, inflammation, demyelination, programmed cell death, or the development of edema. The critical components contributing to CNS response, damage control, and regeneration after TBI are glial cells-in reaction to tissue damage, their activation, hypertrophy, and proliferation occur, followed by the formation of a glial scar. The glial scar creates a barrier in damaged tissue and helps protect the CNS in the acute phase post-injury. However, this process prevents complete tissue recovery in the late/chronic phase by producing permanent scarring, which significantly impacts brain function. Various glial cell types participate in the scar formation, but this process is mostly attributed to reactive astrocytes and microglia, which play important roles in several brain pathologies. Novel technologies including whole-genome transcriptomic and epigenomic analyses, and unbiased proteomics, show that both astrocytes and microglia represent groups of heterogenic cell subpopulations with different genomic and functional characteristics, that are responsible for their role in neurodegeneration, neuroprotection and regeneration. Depending on the representation of distinct
glia subpopulations, the tissue damage as well as the regenerative processes or delayed neurodegeneration after TBI may thus differ in nearby or remote areas or in different brain structures. This
review summarizes TBI as a complex process, where the resultant effect is severity-, region- and time-dependent and determined by the model of the CNS injury and the distance of the explored area from the lesion site. Here, we also discuss findings concerning intercellular signaling, long-term impacts of TBI and the possibilities of novel therapeutical approaches. We believe that a comprehensive study with an emphasis on glial cells, involved in tissue post-injury processes, may be helpful for further research of TBI and be the decisive factor when choosing a TBI model.