Xiaoshuan Tongluo recipe alleviated acute hyperglycemia-enhanced hemorrhagic transformation by regulating microglia polarization in thromboembolic stroke rats

Abstract

Backgrounds: Hemorrhagic transformation (HT) is a complication after stroke and is associated with increased mortality and disability. Hyperglycemia is a risk factor for HT incidence and seriously affects the treatment of stroke. There are no effective drugs to cure HT in the clinic. The Xiaoshuan Tongluo effective component group (XECG) is a Chinese medicine formula reconstituted by active ingredients, which is clinically used for the treatment of stroke. However, the roles of XECG in hyperglycemia-enhanced HT are not clear. This study aims to evaluate the effects of XECG on hyperglycemia-enhanced HT and explore the potential mechanisms. Methods: In this study, a hyperglycemia-induced HT model was used. XECG (100, 200, 400 mg·kg−1) was orally administered for 5 days before the operation, and the incidence of HT was evaluated. Microglia polarization and related signaling pathways were measured to clarify the mechanisms of XECG on hyperglycemia-induced HT. Results: Our results revealed that pretreatment with XECG alleviated neurological deficits and BBB disruption and improved the incidence and severity of HT enhanced by hyperglycemia. Further studies confirmed that XECG regulated microglial polarization by inhibiting the M1 phenotype and promoting the M2 phenotype and inhibited the activation of the HMGB1-RAGE-NF-κB signaling pathway. Conclusions: These results suggested that pretreatment with XECG alleviated hyperglycemia-enhanced HT. XECG may be a potential drug for the treatment of HT.

Keywords

• Xiaoshuan Tongluo recipe
• Stroke
• Hyperglycemia
• Hemorrhagic transformation
• Blood-brain barrier
• Microglia polarization