Inhibition of Exosome Release Alleviates Cognitive Impairment After Repetitive Mild Traumatic Brain Injury.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Tianpeng Hu, Zhaoli Han, Xiangyang Xiong, Meimei Li, Mengtian Guo, Zhenyu Yin, Dong Wang, Lu Cheng, Dai Li, Shishuang Zhang, Lu Wang, Jing Zhao, Qiang Liu, Fanglian Chen, Ping Lei
• Journal: Frontiers in cellular neuroscience (Front Cell Neurosci) Vol. 16 Pg. 832140 ( 2022) ISSN: 1662-5102 [Print] Switzerland
• PMID: 35153676 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Hu, Han, Xiong, Li, Guo, Yin, Wang, Cheng, Li, Zhang, Wang, Zhao, Liu, Chen and Lei.