Valproate improves middle cerebral artery occlusion-induced ischemic cerebral disorders in mice and oxygen-glucose deprivation-induced injuries in microglia by modulating RMRP/PI3K/Akt axis.

Valproate (VPA) is capable of attenuating ischemic stroke (IS)-related disorders in brain tissues. Long non-coding RNAs (lncRNAs) are involved in the progression of IS. In the current study, the role of lncRNA RMRP in the protective effects of VPA against IS was explored. Mice were subjected to middle cerebral artery occlusion (MCAO) model to induce IS injures and then were administrated with VPA. The effects of VPA on infarction area and apoptosis in brain tissues, and the RMRP-regulated PI3K/Akt signaling activity were detected. Thereafter, oxygen-glucose deprivation (OGD) BV-2 cells were used as the in vitro model to further explore the mechanism underlying VPA function. The administration of VPA reduced infarction area and suppressed apoptosis in brain tissues of MCAO mice. VPA also inhibited RMRP expression and activated PI3K/Akt signaling. In OGD BV-2 cells, the treatment of VPA increased viability and attenuated apoptosis, which was associated with the inhibition of RMRP and the activation of PI3K/Akt pathway. Moreover, the induced expression of RMRP blocked the anti-OGD function of VPA, indicating the key role of RMRP inhibition in the effects of VPA on nerve system. Collectively, VPA attenuated MCAO/OGD-induced disorders in mice and microglia. The effects were dependent on the inhibition of RMRP, which subsequently induced the activation of PI3K/Akt signaling.