Mir-17-92 cluster-enriched exosomes improve tissue and functional recovery in rats after traumatic brain injury
Recommended Citation
Zhang Y, Zhang Y, Chopp M, Pang H, Zhang ZG, Mahmood A, and Xiong Y. Mir-17-92 cluster-enriched exosomes improve tissue and functional recovery in rats after traumatic brain injury. J Neurotrauma 2021; 38(14):A112-A113.
Document Type
Conference Proceeding
Publication Date
7-1-2021
Publication Title
J Neurotrauma
Abstract
Exosomes play an important role in intercellular communication by delivering microRNAs to recipient cells. Previous studies have demonstrated that multipotent mesenchymal stromal cell (MSC)-derived exosomes improve functional recovery after experimental traumatic brain injury (TBI). This study was performed to determine whether treatment of TBI with miR-17-92 cluster-enriched exosomes (Exo-17-92) harvested from human bone marrow MSCs transfected with a miR-17-92 cluster plasmid enhances tissue and neurological recovery compared to exosomes derived from MSCs transfected with an empty plasmid vector (Exo-empty). Adult male rats were subjected to a unilateral moderate cortical contusion. Animals received a single intravenous injection ofmiR-17-92 cluster-enriched exosomes (100 lg/rat, Exo-17-92) or control exosomes (100 lg/rat, Exoempty) or Vehicle (phosphate-buffered solution) 1 day after injury. A battery of neurological functional tests were performed weekly after TBI for 5 weeks. Spatial learning and memory were measured on days 31-35 after TBI using the Morris water maze test. All animals were sacrificed 5 weeks after injury. Their brains were processed for histopathological and immunohistochemical analyses of lesion volume, cell loss, angiogenesis, neurogenesis and neuroinflammation. Compared to the vehicle, both Exo-17-92 and Exo-empty treatments significantly improved sensorimotor and cognitive function, reduced neuroinflammation and hippocampal neuronal cell loss, promoted angiogenesis and neurogenesis without altering the lesion volume. Moreover, Exo-17-92 treatment exhibited a significantly more robust therapeutic effect on improvement in functional recovery by reducing neuroinflammation and cell loss, enhancing angiogenesis and neurogenesis than did Exo-empty treatment. In conclusion, exosomes enriched with miR-17-92 cluster have a significantly better effect on im-proving functional recovery after TBI compared to Exo-empty, likely by reducing neuroinflammation and enhancing endogenous angiogenesis and neurogenesis. Engineering specific miRNA in exosomes may provide a novel therapeutic strategy for treatment of TBI.
Volume
38
Issue
14
First Page
A112
Last Page
A113
Comments
doi://10.1089/neu.2021.29111.abstracts