Modified Exosomes Reduce Apoptosis and Ameliorate Neural Deficits Induced by Traumatic Brain Injury

ASAIO Journal : a Peer-reviewed Journal of the American Society for Artificial Internal Organs
Bo Wang, Shuangshuang Han

Abstract

Apoptosis contributes to the pathogenesis of traumatic brain injury (TBI). Engineered exosomes incorporated with therapeutic nuclear acids have been explored for gene therapy for human diseases. The current study sought to investigate the effect of modified exosome-containing plasmids expressing B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X-protein (Bax) short hairpin RNA (shRNA) on apoptosis and neural functions after TBI. C57BL/6J mice were subjected to controlled cortical impact injury and were treated with the modified exosomes. The results showed that modified exosomes attenuated the decrease of myeloid cell leukemia-1 (Mcl-1), X-linked inhibitor of apoptosis protein (XIAP), and Survivin protein levels in the brain and reduced Cytochrome c release from mitochondria to cytosol after TBI. They also attenuated the impairments of miniature excitatory postsynaptic current (mEPSC) and long-term potentiation (LTP) in the hippocampus of TBI mice and improved the motor and cognitive behaviors after TBI. These results suggested that the modified exosomes might reduce apoptosis and ameliorate neural and functional deficits in mouse models of TBI.

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Citations

Aug 9, 2020·Frontiers in Neurology·Vivian A GuedesJessica M Gill
Oct 23, 2019·Frontiers in Molecular Neuroscience·Wanying LiuJunping Zhang
Nov 16, 2020·Biomaterials·Peipei WuHui Qian
Aug 12, 2021·Journal of Extracellular Vesicles·Ricardo C de AbreuLino Ferreira
Sep 18, 2021·Journal of Leukocyte Biology·Nijmeh AlsaadiMelanie J Scott
Feb 21, 2019·Neuroimmunomodulation·Jingjing LiuYutong Sui

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