miR-221 activates Sox11 to reduce brain injury after intracerebral hemorrhage via inhibiting neuroinflammation.

As a global public health issue, intracerebral hemorrhage (ICH) is characterized by high morbidity and mortality. Brain injury following ICH is composed of primary and secondary injury, with the latter being more severe and resulting in increased apoptosis. Sox11 (sex-determining region Y-related high-mobility-group 11), a vital member of the Sox gene family, is broadly discovered in the developing nervous system and may have a vital impact on neurogenesis, neuronal survival, and neurite outgrowth. The level and impacts of Sox11 in brain with ICH remain indistinct. The major objective of the current work was to explore the spatiotemporal expression of Sox11 and its roles in secondary brain injury under the ICH impairment. The ICH rat model was established by injecting autologous blood into the right basal ganglia of male Sprague-Dawley rats. It was observed that Sox11 expression was notably elevated in brain tissue after ICH. The enhancement of Sox11 expression through miR-221 reduced neuronal apoptosis and inflammation in the affected rats. Furthermore, overexpression of Sox11 mitigated ICH-induced brain edema, blood-brain barrier disruption, and cognitive impairments. In contrast, Sox11 knockdown resulted in opposing effects. These findings highlight the crucial role of Sox11 in alleviating secondary brain injury following ICH. Thus, upregulating Sox11 presents a promising therapeutic strategy to reduce secondary brain injury in clinical ICH cases.