Department of Anatomy, Physiology and Genetics, Uniformed Services University , Bethesda, Maryland; Department of Neuroscience, Karolinska Institute, Stockholm, Sweden .
J Neurotrauma. 2017 Sep;34(S1):S44-S52. doi: 10.1089/neu.2017.5317.
Repeated mild traumatic brain injury (rmTBI) caused by playing collision sports or by exposure to blasts during military operations can lead to late onset, chronic diseases such as chronic traumatic encephalopathy (CTE), a progressive neurodegenerative condition that manifests in increasingly severe neuropsychiatric abnormalities years after the last injury. Currently, because of the heterogeneity of the clinical presentation, confirmation of a CTE diagnosis requires post-mortem examination of the brain. The hallmarks of CTE are abnormal accumulation of phosphorylated tau protein, TDP-43 immunoreactive neuronal cytoplasmic inclusions, and astroglial abnormalities, but the pathomechanism leading to these terminal findings remains unknown. Animal modeling can play an important role in the identification of CTE pathomechanisms, the development of early stage diagnostic and prognostic biomarkers, and pharmacological interventions. Modeling the long-term consequences of blast rmTBI in animals is especially challenging because of the complexities of blast physics and animal-to-human scaling issues. This review summarizes current knowledge about the pathobiologies of CTE and rmbTBI and discusses problems as well as potential solutions related to high-fidelity modeling of rmbTBI and determining its long-term consequences.
反复轻度创伤性脑损伤（rmTBI）由参与碰撞运动或在军事行动中暴露于爆炸物引起，可能导致迟发性、慢性疾病，如慢性创伤性脑病（CTE），这是一种进行性神经退行性疾病，在最后一次损伤后数年出现越来越严重的神经精神异常。目前，由于临床表现的异质性，CTE 的确诊需要对大脑进行死后检查。CTE 的特征是磷酸化 tau 蛋白、TDP-43 免疫反应性神经元细胞质内含物和星形胶质细胞异常的异常积累，但导致这些终末发现的发病机制尚不清楚。动物模型在确定 CTE 发病机制、开发早期诊断和预后生物标志物以及药物干预方面可以发挥重要作用。由于爆炸物理的复杂性和动物到人类的比例问题，动物中爆炸 rmTBI 的长期后果建模尤其具有挑战性。本综述总结了 CTE 和 rmbTBI 的病理生物学知识，并讨论了与 rmbTBI 的高保真建模及其长期后果相关的问题以及潜在的解决方案。
