Research Paper Volume 13, Issue 17 pp 21642—21658
Astrocyte-derived exosomes protect hippocampal neurons after traumatic brain injury by suppressing mitochondrial oxidative stress and apoptosis
- 1 Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
- 2 Hebei Institute of Head Trauma, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
- 3 Graduate University, North China University of Science and Technology, Tangshan, Hebei 063000, China
- 4 Department of Cardiology, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
- 5 Department of Endocrinology, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
Received: May 18, 2021 Accepted: August 23, 2021 Published: September 13, 2021https://doi.org/10.18632/aging.203508
How to Cite
Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
In this study, we investigated the mechanisms through which astrocyte-derived exosomes (AS-Exos) alleviate traumatic brain injury (TBI)-induced neuronal defects in TBI model rats and mice. Treatment with AS-Exos alleviated neurobehavioral deficits, cognitive impairment, and brain edema in TBI rats. AS-Exos also significantly reduced neuronal cell loss and atrophy in the TBI rats. AS-Exos significantly reduced oxidative stress and mitochondrial H2O2 levels by increasing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) in the hippocampal neurons of TBI rats. TUNEL-staining assays showed that AS-Exos significantly reduced TBI-induced neuronal apoptosis. Mechanistically, AS-Exos ameliorated oxidative stress by activating Nrf2/HO-1 signaling in the hippocampus of TBI rats. In addition, the neuroprotective effects of AS-Exos were abrogated in brain-specific Nrf2-knockout mice subjected to TBI. These findings demonstrate that AS-Exos protects against TBI-induced oxidative stress and neuronal apoptosis by activating Nrf2 signaling in both rat and mouse models.