Abstract
Traumatic brain injury (TBI) is a serious public health problem worldwide, which could lead to an extremely high percentage of mortality and disability. Current treatment strategies mainly concentrate on neuronal protection and reconstruction, among them, exogenous neural stem cell (NSC) transplantation has long been regarded as the most effective curative treatment. However, due to secondary trauma, transplant rejection, and increased incidence of brain malignant tumor, a non-invasive therapy that enhanced endogenous neurogenesis was more suitable for TBI treatment. Our previous work has shown that miR-132 overexpression could improve neuronal differentiation of NSCs in vitro and in vivo. So, we engineered a new kind of AAV vector named AAV-PHP.eB which can transfect brain parenchyma through intravenous injection to overexpress miR-132 in brain after TBI. We found that miR-132 overexpression could reduce impact volume, promote neurogenesis in the dentate gyrus (DG), accelerate neuroblast migrating into the impact cortex, ameliorate microglia-mediated inflammatory reaction, and ultimately restore learning memory function. Our results revealed that AAV-PHP.eB-based miR-132 overexpression could improve endogenous tissue repairment and release clinical symptoms after traumatic brain injury. This work would provide a new therapeutic strategy for TBI treatment and other neurological disorders characterized by markable neuronal loss and memory impairment. miR-132 overexpression accelerates endogenous neurogenesis and releases TBI-induced tissue repairment and memory impairment. Controlled cortical impact onto the cortex would induce serious cortical injury and microglia accumulation in both cortex and hippocampus. Moreover, endogenous neuroblast could migrate around the injury core. miR-132 overexpression could accelerate neuroblast migration toward the injury core and decreased microglia accumulation in the ipsilateral cortex and hippocampus. miR-132 could be a suitable target on neuroprotective therapy after TBI.