Butylphthalide has an Anti-Inflammatory Role in Spinal Cord Injury by Promoting Macrophage/Microglia M2 Polarization via p38 Phosphorylation

Study Design. An experimental animal study of treatment of spinal cord injury (SCI). Objective. This report aims to evaluate the in vivo effects of butylphthalide NBP on SCI biology and to explore its potential mechanism. Summary of Background Data. SCI causes great damage to humans. The inflammatory and reconstructive processes after SCI is regulated by activation of astroglial and microglial cells. Activated microglia/macrophages can be divided into M2 (anti-inflammatory) and M1 (pro-inflammatory) phenotypes. Butylphthalide (3-n-butylphthalide or NBP) treatment can significantly alleviate ischemic brain damage, and further study has confirmed that central neuroprotective effects can be realized by converting M1 polarized microglia/macrophages to the M2 phenotype. Thus far, it remains unknown whether NBP can modulate the transition of macrophages/microglia between the M1 and M2 phenotypes. Methods. We randomly divided male mice into three groups (sham group, SCI group, SCI+ NBP group). Molecular and histological tests were performed to detect the macrophage/microglia polarization as well as the potential mechanism of NBP in vivo and in vitro . Result. It was found that NBP treatment significantly attenuated the motor dysfunction and neuronal apoptosis induced by SCI. Treatment with NBP could also reduce pro-inflammatory cytokine release after SCI and could facilitate macrophage/microglia M2 polarization and inhibit M1 polarization after SCI. To verify the findings in animal experiments, we examined the effect of NBP on BV2 cell polarization, the results showed that NBP treatment could enhance M2 polarization and inhibit M1 polarization, and that M2 polarization occurred in a p38-dependent manner. Conclusion. NBP plays an important role in the anti-inflammatory response in SCI via the facilitation of macrophage/microglia M2 polarization as well as the inhibition of macrophage/microglia M1 polarization. The M2 polarization of macrophages/microglia occurs via activation of p38 pathway. Level of Evidence: 3