Zhou Yunxiang, Chen Qiang, Wang Yali, Wu Haijian, Xu Weilin, Pan Yuanbo, Gao Shiqi, Dong Xiao, Zhang John H, Shao Anwen
Department of Surgical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Front Neurosci. 2020 Jun 9;14:581. doi: 10.3389/fnins.2020.00581. eCollection 2020.
Traumatic brain injury (TBI) represents one of the major causes of death worldwide and leads to persisting neurological deficits in many of the survivors. One of the most significant long-term sequelae deriving from TBI is neurodegenerative disease, which is a group of incurable diseases that impose a heavy socio-economic burden. However, mechanisms underlying the increased susceptibility of TBI to neurodegenerative disease remain elusive. The neurovascular unit (NVU) is a functional unit composed of neurons, neuroglia, vascular cells, and the basal lamina matrix. The key role of NVU dysfunction in many central nervous system diseases has been revealed. Studies have proved the presence of prolonged structural and functional abnormalities of the NVU after TBI. Moreover, growing evidence suggests impaired NVU function is also implicated in neurodegenerative diseases. Therefore, we propose the Neurovascular Unit Dysfunction (NVUD) Hypothesis, in which the persistent NVU dysfunction is thought to underlie the development of post-TBI neurodegeneration. We deduce NVUD Hypothesis through relational inference and supporting evidence, and suggest continued NVU abnormalities following TBI serve as the pathophysiological substrate and trigger yielding chronic neuroinflammation, proteinopathies and oxidative stress, consequently leading to the progression of neurodegenerative diseases. The NVUD Hypothesis may provide potential treatment and prevention strategies for TBI and late-onset neurodegenerative diseases.
创伤性脑损伤（TBI）是全球主要的死亡原因之一，会导致许多幸存者出现持续性神经功能缺损。TBI最显著的长期后遗症之一是神经退行性疾病，这是一组无法治愈的疾病，会带来沉重的社会经济负担。然而，TBI易患神经退行性疾病的潜在机制仍不清楚。神经血管单元（NVU）是一个由神经元、神经胶质、血管细胞和基膜基质组成的功能单元。NVU功能障碍在许多中枢神经系统疾病中的关键作用已被揭示。研究证明，TBI后NVU存在长期的结构和功能异常。此外，越来越多的证据表明，NVU功能受损也与神经退行性疾病有关。因此，我们提出了神经血管单元功能障碍（NVUD）假说，即认为持续性NVU功能障碍是TBI后神经退行性变发展的基础。我们通过关系推理和支持证据推导出NVUD假说，并提出TBI后NVU持续异常作为病理生理基础和触发因素，会引发慢性神经炎症、蛋白病和氧化应激，进而导致神经退行性疾病的进展。NVUD假说可能为TBI和迟发性神经退行性疾病提供潜在的治疗和预防策略。
