CK2 inhibitor DMAT ameliorates spinal cord injury by increasing autophagy and inducing anti-inflammatory microglial polarization

Spinal cord injury (SCI) is a destructive and disabling nerve injury from which complete recovery has not yet been achieved due to complex pathology. Casein kinase II (CK2) is a pleiotropic serine/threonine protein kinase that plays an essential role in the nervous system. This study aimed to investigate the role of CK2 in SCI to understand the pathogenesis of SCI and explore new therapeutic methods. The SCI rat model of C5 unilateral clamp was established by modified clamp method in male adult SD rats. Then, CK2 inhibitor DMAT was used to treat SCI rats, and the behaviour, pathological changes in the spinal cord and microglial polarization were analysed. Additionally, the effects of DMAT on the polarization and autophagy of microglial BV-2 cells were investigated in vitro, and the effects of BV-2 polarization on spinal cord neuronal cells were analysed by Transwell coculture. Results showed that DMAT significantly increased the BBB score, improved histopathological injury, decreased the expression of inflammatory cytokines, and promoted M2 polarization of microglia in SCI rats. In vitro experiments further confirmed that DMAT could promote the polarization of BV-2 to the M2 type, promote autophagy, and reverse the LPS-induced decline in cell viability and increase in apoptosis of neuronal cells. The use of 3-MA confirmed that autophagy plays an important role in DMAT promoting M2 polarization of BV-2 to improve neuronal cell viability. In conclusion, CK2 inhibitor DMAT improved SCI by inducing anti-inflammatory polarization of microglia through autophagy and is a potential therapeutic target for SCI.