Hu Tianpeng, Han Zhaoli, Xiong Xiangyang, Li Meimei, Guo Mengtian, Yin Zhenyu, Wang Dong, Cheng Lu, Li Dai, Zhang Shishuang, Wang Lu, Zhao Jing, Liu Qiang, Chen Fanglian, Lei Ping
Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China.
Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
Front Cell Neurosci. 2022 Jan 27;16:832140. doi: 10.3389/fncel.2022.832140. eCollection 2022.
Repetitive mild traumatic brain injury (rmTBI) is closely associated with chronic traumatic encephalopathy (CTE). Neuroinflammation and neuropathological protein accumulation are key links to CTE progression. Exosomes play important roles in neuroinflammation and neuropathological protein accumulation and spread. Here, we explored the role of brain-derived exosomes (BDEs) in mice with rmTBI and how the inhibition of BDE release contributes to neuroprotection.
GW4869 was used to inhibit exosome release, and behavioural tests, PET/CT and western blotting were conducted to explore the impact of this inhibition from different perspectives. We further evaluated cytokine expression by Luminex and microglial activation by immunofluorescence in mice with rmTBI after exosome release inhibition.
Inhibition of BDE release reversed cognitive impairment in mice with rmTBI, enhanced glucose uptake and decreased neuropathological protein expression. Inhibition of BDE release also changed cytokine production trends and enhanced microglial proliferation.
In this study, we found that BDEs are key factor in cognitive impairment in mice with rmTBI and that microglia are the main target of BDEs. Thus, inhibition of exosome release may be a new strategy for improving CTE prognoses.
重复性轻度创伤性脑损伤（rmTBI）与慢性创伤性脑病（CTE）密切相关。神经炎症和神经病理蛋白积累是CTE进展的关键环节。外泌体在神经炎症、神经病理蛋白积累和传播中发挥重要作用。在此，我们探讨了脑源性外泌体（BDEs）在rmTBI小鼠中的作用以及抑制BDE释放如何有助于神经保护。
使用GW4869抑制外泌体释放，并通过行为测试、PET/CT和蛋白质印迹从不同角度探讨这种抑制的影响。我们进一步通过Luminex评估细胞因子表达，并通过免疫荧光评估rmTBI小鼠在外泌体释放抑制后的小胶质细胞激活情况。
抑制BDE释放可逆转rmTBI小鼠的认知障碍，增强葡萄糖摄取并降低神经病理蛋白表达。抑制BDE释放还改变了细胞因子产生趋势并增强了小胶质细胞增殖。
在本研究中，我们发现BDEs是rmTBI小鼠认知障碍的关键因素，且小胶质细胞是BDEs的主要靶点。因此，抑制外泌体释放可能是改善CTE预后的一种新策略。
