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首页> 外文期刊>The Canadian Journal of Neurological Sciences: le Journal Canadien des Sciences Neurologiques >DNA damage and brain trauma: a clue to pathophysiology and biomarker development
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DNA damage and brain trauma: a clue to pathophysiology and biomarker development

机译：DNA损伤和脑外创伤：病理生理学和生物标志物发育的线索

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摘要

Mild traumatic brain injury (mTBI) or concussion is a very common occurrence in contact sports, and can cause brain damage with long-term symptoms, including depression, aggression, memory loss, and an increased risk of neurodegeneration later in life. Recently, there has been increased attention towards concussion in sport both in research and media, however the nature and pathophysiology of mTBI-induced neurodegeneration remain unknown. The objective of this study is to identify early pathophysiological markers of TBI. This study used a collection of donated postmortem brains with a history of repetitive mTBI in contact sports and non-TBI control brains. Nanostring ncounter’s immune panel was used to evaluate gene expression, and results showed that brains with a history of TBI tended to group with significantly older brains with no history of TBI in regards to their immune profile. Further analysis of this expression panel revealed that genes associated with senescence and secretory phenotype were upregulated in brains with a history of mTBI. Additionally, immunohistochemistry for γ-H2AX (a marker for double stranded DNA breaks) showed that brains with a history of repetitive TBI accumulated a spectrum of DNA damages not present in controls. This damage was widespread and involved mainly glial cells including oligodendrocytes, and astrocytes. The latter showed morphological changes reminiscent of senescence, including soma swelling and beading of processes. Further, these changes were accompanied by translocation of structural nuclear proteins. These changes preceded the appearance of abnormal protein deposition in the brain. Overall, these results suggest that DNA damage and cellular senescence are upstream events in the manifestation of post-mTBI symptoms and pathology, and represent promising opportunities for discovery of biomarkers for early TBI detection and follow-up of progression.
机译：轻度创伤性脑损伤（MTBI）或脑震荡是联系运动的非常常见的发生，并且可能导致长期症状导致脑损伤，包括抑郁，侵略，记忆力丧失，以及生活中的神经变性的风险增加。最近，在研究和培养基中，在运动中脑震荡的关注，但MTBI诱导的神经变性的性质和病理生理学仍然是未知的。本研究的目的是鉴定TBI的早期病理生理标志物。本研究采用了一系列捐赠的后期大脑，其历史与联系运动和非TBI控制大脑中的重复MTBI历史。用于评估基因表达的纳米麻疹的免疫面板，结果表明，TBI历史的脑力趋于较旧的大脑，其免疫剖面上没有TBI的历史。对该表达面板的进一步分析显示，衰老和分泌表型相关的基因在具有MTBI的历史中的脑中上调。另外，用于γ-H2AX的免疫组织化学（双链DNA断裂的标志物）显示，具有重复TBI历史的大脑累积了不存在于对照中的DNA损伤的光谱。这种损害是普遍的，主要涉及胶质细胞，包括少突胶质细胞和星形胶质细胞。后者表现出形态变化让人想起衰老，包括躯体肿胀和过程的珠子。此外，这些变化伴有结构核蛋白的易位。这些变化在脑中异常蛋白质沉积的外观。总体而言，这些结果表明DNA损伤和细胞衰老是MTBI后症状和病理学表现的上游事件，并且代表了对早期TBI检测和进展后续行动的生物标志物发现的有希望的机会。

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