Elevated expression of miR-302 cluster improves traumatic brain injury by inhibiting phosphorylation of connexin43 via ERK signaling

We examined apoptosis and ERK1/2 and connexin43 phosphorylation in SH-SY5Y cells undergoing pulsatile shear stress treatment. We assessed expression of miR-302 cluster members and exogenously expressed miR-302 cluster in stressed cells to determine its effect on ERK1/2 and connexin43 phosphorylation. Finally, we investigated the effects of elevated miR-302 expression on cognitive function and brain damage in TBI rats generated by the controlled cortical impact method. Pulsatile shear stress leads to increased apoptosis and upregulation of ERK1/2 and connexin43 phosphorylation in vitro. Additionally, pulsatile shear stress significantly suppressed miR-302 expression and exogenously expression of miR-302 cluster inhibited ERK1/2 and connexin43 phosphorylation. Finally, elevated expression of miR-302 cluster not only improved cognitive function of TBI rats but also attenuated brain damage by suppressing edema and reducing contusion volume. Our study suggests that miR-302 protects rats from TBI induced brain damage and cognitive impairment and may represent an effective therapeutic strategy for TBI.
Source: Journal of Chemical Neuroanatomy - Category: Neuroscience Source Type: research