Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, University of Pittsburgh, Pittsburgh, PA, United States; Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States.
Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, University of Pittsburgh, Pittsburgh, PA, United States; Department of Neurology, University of Pittsburgh, Pittsburgh, PA, United States; Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States.
Exp Neurol. 2020 Jun;328:113257. doi: 10.1016/j.expneurol.2020.113257. Epub 2020 Feb 21.
The blood-brain barrier (BBB) is a complex and dynamic physiological interface between brain parenchyma and cerebral vasculature. It is composed of closely interacting cells and signaling molecules that regulate movement of solutes, ions, nutrients, macromolecules, and immune cells into the brain and removal of products of normal and abnormal brain cell metabolism. Dysfunction of multiple components of the BBB occurs in aging, inflammatory diseases, traumatic brain injury (TBI, severe or mild repetitive), and in chronic degenerative dementing disorders for which aging, inflammation, and TBI are considered risk factors. BBB permeability changes after TBI result in leakage of serum proteins, influx of immune cells, perivascular inflammation, as well as impairment of efflux transporter systems and accumulation of aggregation-prone molecules involved in hallmark pathologies of neurodegenerative diseases with dementia. In addition, cerebral vascular dysfunction with persistent alterations in cerebral blood flow and neurovascular coupling contribute to brain ischemia, neuronal degeneration, and synaptic dysfunction. While the idea of TBI as a risk factor for dementia is supported by many shared pathological features, it remains a hypothesis that needs further testing in experimental models and in human studies. The current review focusses on pathological mechanisms shared between TBI and neurodegenerative disorders characterized by accumulation of pathological protein aggregates, such as Alzheimer's disease and chronic traumatic encephalopathy. We discuss critical knowledge gaps in the field that need to be explored to clarify the relationship between TBI and risk for dementia and emphasize the need for longitudinal in vivo studies using imaging and biomarkers of BBB dysfunction in people with single or multiple TBI.
血脑屏障（BBB）是脑实质和脑血管之间复杂而动态的生理界面。它由密切相互作用的细胞和信号分子组成，调节溶质、离子、营养物质、大分子和免疫细胞进入大脑以及清除正常和异常脑细胞代谢产物的运动。在衰老、炎症性疾病、创伤性脑损伤（TBI，严重或轻度反复）以及慢性退行性痴呆性疾病中，BBB 的多个成分发生功能障碍，其中衰老、炎症和 TBI 被认为是危险因素。TBI 后 BBB 通透性的改变导致血清蛋白渗漏、免疫细胞涌入、血管周围炎症以及外排转运蛋白系统的损害和与痴呆相关的神经退行性疾病标志性病理相关的聚集倾向分子的积累。此外，脑血管功能障碍伴有持续的脑血流和神经血管耦联改变导致脑缺血、神经元变性和突触功能障碍。虽然 TBI 作为痴呆的危险因素的观点得到了许多共同的病理特征的支持，但这仍然是一个需要在实验模型和人类研究中进一步验证的假设。目前的综述重点讨论了 TBI 和以病理性蛋白聚集体积累为特征的神经退行性疾病之间的共同病理机制，如阿尔茨海默病和慢性创伤性脑病。我们讨论了该领域的关键知识差距，需要进一步探索以阐明 TBI 与痴呆风险之间的关系，并强调需要使用单或多次 TBI 患者的成像和 BBB 功能障碍的生物标志物进行纵向体内研究。
