Developing Biomarkers of Mild Traumatic Brain Injury: Promise and Progress of CNS-Derived Exosomes.
Developing Biomarkers of Mild Traumatic Brain Injury: Promise and Progress of CNS-Derived Exosomes.
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DOI：
10.3389/fneur.2021.698206
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发表时间：
2021
影响因子：
3.4
通讯作者：
Risbrough VB
中科院分区：
文献类型：
--
作者：
Vaughn MN;Winston CN;Levin N;Rissman RA;Risbrough VB
轻度创伤性脑损伤（mTBI）是平民和军人的常见损伤。虽然大多数人在mTBI后恢复，但有些人继续表现出长期症状以及神经退行性疾病和神经精神疾病的风险增加。目前，诊断TBI严重程度主要依赖于自我报告和主观症状，诊断或预后工具有限。脑源性外泌体是细胞外囊泡的一种形式，可以通过帮助诊断以及以相对较低的患者负担预测结果来提供解释损伤状态的解决方案。释放到循环中的外泌体含有可以分离和定量的蛋白质和RNA货物，为外泌体来源的分子状态提供了分子窗口。在这里，我们检查了研究外泌体，特别是神经元和星形胶质细胞来源的外泌体的效用的当前文献，以鉴定损伤严重程度、轨迹和功能结果的蛋白质和miRNA生物标志物。目前的证据支持这些新兴的新工具在大脑对创伤性损伤做出反应时捕获进入大脑的分子窗口的潜力，但是在未来的研究中必须解决一些限制。目前大多数研究都是相对较小的横断面研究;需要跨损伤严重程度和人群的前瞻性纵向研究来跟踪损伤后外泌体货物的变化。标准化的外泌体分离以及从CNS特异性组织来源鉴定/分离外泌体的进展将提高对货物变化的机械理解以及发现的可靠性。外泌体也刚刚开始用于模型系统，以了解TBI相关货物的功能效应，如毒性。最后，将外泌体货物变化与神经元病理和认知变化的客观标志物联系起来，对于验证这些工具以提供对TBI后损伤和恢复状态的见解至关重要。
Mild traumatic brain injuries (mTBI) are common injuries across civilian and military populations. Although most individuals recover after mTBI, some individuals continue to show long-term symptoms as well as increased risk for neurodegenerative and neuropsychiatric disorders. Currently, diagnosing TBI severity relies primarily on self-report and subjective symptoms, with limited tools for diagnosis or prognosis. Brain-derived exosomes, a form of extracellular vesicle, may offer a solution for interpreting injury states by aiding in diagnosis as well as outcome prediction with relatively low patient burden. Exosomes, which are released into circulation, contain both protein and RNA cargo that can be isolated and quantified, providing a molecular window into molecular status of the exosome source. Here we examined the current literature studying the utility of exosomes, in particular neuronal- and astrocyte-derived exosomes, to identify protein and miRNA biomarkers of injury severity, trajectory, and functional outcome. Current evidence supports the potential for these emerging new tools to capture an accessible molecular window into the brain as it responds to a traumatic injury, however a number of limitations must be addressed in future studies. Most current studies are relatively small and cross sectional; prospective, longitudinal studies across injury severity, and populations are needed to track exosome cargo changes after injury. Standardized exosome isolation as well as advancement in identifying/isolating exosomes from CNS-specific tissue sources will improve mechanistic understanding of cargo changes as well as reliability of findings. Exosomes are also just beginning to be used in model systems to understand functional effects of TBI-associated cargo such as toxicity. Finally linking exosome cargo changes to objective markers of neuronal pathology and cognitive changes will be critical in validating these tools to provide insights into injury and recovery states after TBI.
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影响因子：
4.6
作者：
Bhomia M;Balakathiresan NS;Wang KK;Papa L;Maheshwari RK
通讯作者：
Maheshwari RK
影响因子：
--
作者：
Bryden, Daniel W.;Tilghman, Jessica I.;Hinds, Sidney R., II
通讯作者：
Hinds, Sidney R., II
影响因子：
3.4
作者：
Garcia JM;Stillings SA;Leclerc JL;Phillips H;Edwards NJ;Robicsek SA;Hoh BL;Blackburn S;Doré S
通讯作者：
Doré S
DOI：
10.1042/bcj20160082
发表时间：
2016-08-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Bishop P;Rocca D;Henley JM
通讯作者：
Henley JM
DOI：
10.1073/pnas.1209414109
发表时间：
2012-07-31
影响因子：
11.1
作者：
Fabbri, Muller;Paone, Alessio;Croce, Carlo M.
通讯作者：
Croce, Carlo M.