Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Center of Excellence for Aging and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Stem Cells Transl Med. 2022 Dec 30;11(12):1196-1209. doi: 10.1093/stcltm/szac072.
Amyotrophic lateral sclerosis (ALS) is a debilitating disease with poor prognosis. The pathophysiology of ALS is commonly debated, with theories involving inflammation, glutamate excitotoxity, oxidative stress, mitochondria malfunction, neurofilament accumulation, inadequate nutrients or growth factors, and changes in glial support predominating. These underlying pathological mechanisms, however, act together to weaken the blood brain barrier and blood spinal cord barrier, collectively considered as the blood central nervous system barrier (BCNSB). Altering the impermeability of the BCNSB impairs the neurovascular unit, or interdependent relationship between the brain and advances the concept that ALS is has a significant neurovascular component contributing to its degenerative presentation. This unique categorization of ALS opens a variety of treatment options targeting the reestablishment of BCNSB integrity. This review will critically assess the evidence implicating the significant neurovascular components of ALS pathophysiology, while also offering an in-depth discussion regarding the use of stem cells to repair these pathological changes within the neurovascular unit.
肌萎缩侧索硬化症(ALS)是一种预后不良的致残性疾病。ALS 的病理生理学目前仍存在争议,涉及炎症、谷氨酸兴奋性毒性、氧化应激、线粒体功能障碍、神经丝积累、营养或生长因子不足以及神经胶质支持改变等理论。然而,这些潜在的病理机制共同作用,削弱了血脑屏障和血脊髓屏障,这两者通常被认为是血中枢神经系统屏障(BCNSB)。改变 BCNSB 的通透性会损害神经血管单元,或破坏大脑和血管之间的相互依存关系,并提出 ALS 具有显著的神经血管成分,这有助于其退行性表现的概念。ALS 的这种独特分类为针对 BCNSB 完整性重建的各种治疗选择提供了机会。本综述将批判性地评估 ALS 病理生理学中涉及显著神经血管成分的证据,同时深入讨论使用干细胞来修复神经血管单元中的这些病理变化。