Blood-Brain Barrier Dysfunction as a Hallmark Pathology in Chronic Traumatic Encephalopathy
Blood-Brain Barrier Dysfunction as a Hallmark Pathology in Chronic Traumatic Encephalopathy
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DOI：
10.1093/jnen/nlw036
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发表时间：
2016-07-01
影响因子：
3.2
通讯作者：
Campbell, Matthew
中科院分区：
文献类型：
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作者：
Doherty, Colin P.;O'Keefe, Eoin;Campbell, Matthew
慢性创伤性脑病（CTE）是一种与重复性轻度创伤性脑损伤相关的神经退行性疾病。近年来，人们的注意力集中在新出现的证据，将CTE的发展与运动员和军事人员的脑震荡损伤联系起来;然而，CTE的潜在分子病理学仍不清楚。在这里，我们提供的证据表明，在CTE的情况下，血脑屏障（BBB）在密集的血管周围p-Tau积聚的区域被破坏。血脑屏障相关的紧密连接组件claudin-5和闭锁小带-1的免疫反应模式显着不连续或不存在的血管周围的p-Tau沉积的区域，也有血脑屏障在这些病灶的免疫组化证据。由于该患者在临床上被诊断为进行性核上性麻痹（PSP），我们也认为CTE的改变似乎与PSP患者大脑中的CTE改变不同。本报告首次描述了病理证实的CTE病例中的BBB功能障碍，并表明脑震荡后级联事件中的血管成分可能最终导致进展性退行性疾病的发展。BBB功能障碍可能代表疑似有CTE发展风险的活体受试者中神经功能障碍的相关性。
Chronic traumatic encephalopathy (CTE) is a neurodegenerative condition associated with repetitive mild traumatic brain injury. In recent years, attention has focused on emerging evidence linking the development of CTE to concussive injuries in athletes and military personnel; however, the underlying molecular pathobiology of CTE remains unclear. Here, we provide evidence that the blood brain barrier (BBB) is disrupted in regions of dense perivascular p-Tau accumulation in a case of CTE. Immunoreactivity patterns of the BBB-associated tight junction components claudin-5 and zonula occludens-1 were markedly discontinuous or absent in regions of perivascular p-Tau deposition; there was also immunohistochemical evidence of a BBB in these foci. Because the patient was diagnosed premortem clinically as having progressive supranuclear palsy (PSP), we also compromised that the CTE alterations appear to be distinct from those in the brain of a patient with PSP. This report represents the first description of BBB dysfunction in a pathologically proven CTE case and suggests a vascular component in the postconcussion cascade of events that may ultimately lead to development of a progressive degenerative disorder. BBB dysfunction may represent a correlate of neural dysfunction in live subjects suspected of being at risk for development of CTE.