Oxymatrine ameliorates white matter injury by modulating gut microbiota after intracerebral hemorrhage in mice

Abstract

Abstract Background White matter injury (WMI) significantly affects neurobehavioral recovery in intracerebral hemorrhage (ICH) patients. Gut dysbiosis plays an important role in the pathogenesis of neurological disorders. Oxymatrine (OMT) has therapeutic effects on inflammation-mediated diseases. Whether OMT exerts therapeutic effects on WMI after ICH and the role of gut microbiota in this process is largely unknown. Methods ICH model was established by collagenase IV injection. OMT was daily administrated via oral gavage after ICH. Neurological deficits, WMI, the severity of corticospinal tract (CST) injury, intestinal barrier function and systemic inflammation were investigate after ICH. Microbial 16S rRNA sequencing was performed to reveal the dynamic microbial profiles. Fecal microbiota transplantation (FMT) was performed to elucidate the role of gut microbiota in the pathogenesis of ICH. Results OMT promoted a better long-term neurological function recovery and ameliorated axonal demyelination, microgliosis and glial scar formation in the peri-hematoma region and distal CST in the chronic phase after ICH. The significant and persistent alterations of gut microbial composition induced by ICH, which lasted more than two weeks, were obviously regulated by OMT via increasing the species richness and diversity. Additionally, treatment with OMT alleviated intestinal barrier dysfunction, accompanied by a significant down-regulation of the levels of pro-inflammatory cytokines. Correlation analysis revealed that gut microbiota alteration was correlated with inflammation, intestinal barrier permeability, and neurological deficits after ICH. Moreover, the therapeutic effects of OMT on ICH-induced WMI and intestinal barrier disruption were transferrable by fecal microbiota transplantation (FMT). Conclusion Our study showed that OMT ameliorates ICH-induced WMI, neurological deficits and intestinal barrier disruption, and OMT-modulated gut microbiota plays an important role in the underlying mechanism.