Harry S. Truman Memorial Veterans Hospital, U.S. Department of Veterans Affairs, Columbia, MO, USA.
Department of Neurology, and the Center for Translational Neuroscience, School of Medicine, University of Missouri, Columbia, MO, USA.
Neuroscientist. 2020 Apr;26(2):134-155. doi: 10.1177/1073858419848293. Epub 2019 May 16.
Traumatic brain injury (TBI) is a major health problem in the United States, which affects about 1.7 million people each year. Glial cells, T-cells, and mast cells perform specific protective functions in different regions of the brain for the recovery of cognitive and motor functions after central nervous system (CNS) injuries including TBI. Chronic neuroinflammatory responses resulting in neuronal death and the accompanying stress following brain injury predisposes or accelerates the onset and progression of Alzheimer's disease (AD) in high-risk individuals. About 5.7 million Americans are currently living with AD. Immediately following brain injury, mast cells respond by releasing prestored and preactivated mediators and recruit immune cells to the CNS. Blood-brain barrier (BBB), tight junction and adherens junction proteins, neurovascular and gliovascular microstructural rearrangements, and dysfunction associated with increased trafficking of inflammatory mediators and inflammatory cells from the periphery across the BBB leads to increase in the chronic neuroinflammatory reactions following brain injury. In this review, we advance the hypothesis that neuroinflammatory responses resulting from mast cell activation along with the accompanying risk factors such as age, gender, food habits, emotional status, stress, allergic tendency, chronic inflammatory diseases, and certain drugs can accelerate brain injury-associated neuroinflammation, neurodegeneration, and AD pathogenesis.
创伤性脑损伤（TBI）是美国的一个主要健康问题，每年约有 170 万人受到影响。神经胶质细胞、T 细胞和肥大细胞在中枢神经系统（CNS）损伤后，包括 TBI，在大脑的不同区域发挥特定的保护功能，以恢复认知和运动功能。慢性神经炎症反应导致神经元死亡，并伴有脑损伤后的应激，使阿尔茨海默病（AD）的高危人群更容易发病和加速发病进程。目前，约有 570 万美国人患有 AD。脑损伤后，肥大细胞通过释放预先储存和预先激活的介质来响应，并将免疫细胞募集到中枢神经系统。血脑屏障（BBB）、紧密连接和黏附连接蛋白、神经血管和神经胶质微血管结构重排，以及与炎症介质和炎症细胞从外周向 BBB 过度运输相关的功能障碍，导致脑损伤后的慢性神经炎症反应增加。在这篇综述中，我们提出了一个假设，即肥大细胞激活引起的神经炎症反应，以及年龄、性别、饮食习惯、情绪状态、应激、过敏倾向、慢性炎症性疾病和某些药物等伴随的危险因素，可以加速与脑损伤相关的神经炎症、神经退行性变和 AD 发病机制。
