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.

中文翻译：

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持续性神经血管单元功能障碍：脑外伤后迟发性神经变性的病理生理基础和触发因素

创伤性脑损伤 (TBI) 是全球死亡的主要原因之一，并导致许多幸存者出现持续的神经功能缺陷。TBI 引起的最重要的长期后遗症之一是神经退行性疾病，这是一组造成沉重社会经济负担的不治之症。然而，TBI 对神经退行性疾病的易感性增加的机制仍然难以捉摸。神经血管单元（NVU）是由神经元、神经胶质细胞、血管细胞和基底层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，我们提出神经血管单元功能障碍（NVUD）假说，其中持续的 NVU 功能障碍被认为是 TBI 后神经变性发展的基础。我们通过相关推理和支持证据推导出 NVUD 假说，并表明 TBI 后持续的 NVU 异常是病理生理学基础，引发慢性神经炎症、蛋白质病和氧化应激，从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。