Department of Clinical and Health Psychology, College of Health and Health Professions, University of Florida, PO Box 100165, Gainesville, FL 32610, USA.
Department of Neurology, School of Medicine, University of Florida, 2000 SW Archer Rd, Gainesville, FL 32610, USA.
Neurosci Biobehav Rev. 2018 Jan;84:316-324. doi: 10.1016/j.neubiorev.2017.08.016. Epub 2017 Aug 30.
Traumatic brain injury (TBI) is an increasingly important issue among veterans, athletes and the general public. Difficulties with sleep onset and maintenance are among the most commonly reported symptoms following injury, and sleep debt is associated with increased accumulation of beta amyloid (Aβ) and phosphorylated tau (p-tau) in the interstitial space. Recent research into the glymphatic system, a lymphatic-like metabolic clearance mechanism in the central nervous system (CNS) which relies on cerebrospinal fluid (CSF), interstitial fluid (ISF), and astrocytic processes, shows that clearance is potentiated during sleep. This system is damaged in the acute phase following mTBI, in part due to re-localization of aquaporin-4 channels away from astrocytic end feet, resulting in reduced potential for waste removal. Long-term consequences of chronic dysfunction within this system in the context of repetitive brain trauma and insomnia have not been established, but potentially provide one link in the explanatory chain connecting repetitive TBI with later neurodegeneration. Current research has shown p-tau deposition in perivascular spaces and along interstitial pathways in chronic traumatic encephalopathy (CTE), pathways related to glymphatic flow; these are the main channels by which metabolic waste is cleared. This review addresses possible links between mTBI-related damage to glymphatic functioning and physiological changes found in CTE, and proposes a model for the mediating role of sleep disruption in increasing the risk for developing CTE-related pathology and subsequent clinical symptoms following repetitive brain trauma.
创伤性脑损伤（TBI）在退伍军人、运动员和普通公众中是一个日益重要的问题。睡眠起始和维持困难是受伤后最常报告的症状之一，睡眠债与β淀粉样蛋白（Aβ）和磷酸化tau（p-tau）在细胞间隙中的积累增加有关。最近对脑淋巴系统的研究表明，脑淋巴系统是中枢神经系统（CNS）中的一种类淋巴代谢清除机制，依赖于脑脊液（CSF）、细胞间液（ISF）和星形胶质细胞过程，清除作用在睡眠时增强。在 mTBI 后的急性期，该系统受损，部分原因是水通道蛋白-4 通道从星形胶质细胞终足重新定位，导致废物清除的潜力降低。在重复脑外伤和失眠的情况下，该系统长期功能障碍的长期后果尚未确定，但可能为重复 TBI 与随后的神经退行性变之间的解释链提供了一个联系。目前的研究表明，在慢性创伤性脑病变（CTE）中，p-tau 沉积在血管周围空间和细胞间途径中，与脑淋巴系统流动途径相关；这些是清除代谢废物的主要途径。这篇综述探讨了 mTBI 相关的脑淋巴系统功能障碍与 CTE 中发现的生理变化之间的可能联系，并提出了一个模型，用于解释睡眠中断在增加重复性脑创伤后发生 CTE 相关病理和随后临床症状的风险中的中介作用。
