Objective This study aimed to clarify the neuroprotective effect of dexmedetomidine (DEX) against cerebral ischemia reperfusion injury (CIRI) and its underlying mechanism using network pharmacology and in vivo validation. Methods Network pharmacology was employed to explore the mechanism underlying DEX-mediated alleviation of CIRI. A rat CIRI model was established using the suture-occlusion method. Neurological scoring and behavioral assessments were conducted to evaluate neurological and motor functions; histological examination was performed to observe brain tissue and blood–brain barrier (BBB) injury. Western blotting and immunofluorescence analysis were utilized to assess the protein levels of factors associated with BBB integrity. Results Network pharmacology analysis revealed that DEX may exert a protective effect against CIRI through the AMPK/mTOR signaling pathway. DEX treatment significantly attenuated CIRI-induced impairments in neurological function and motor performance. Specifically, DEX upregulated the protein expression levels of P-AMPK/AMPK ratio, beclin 1, LC3 II/I, and ZO-1, whereas the P-mTOR/mTOR ratio and P62 were significantly downregulated, and cerebral tissue injury was alleviated. Conclusion DEX exerts a significant protective effect against BBB injury in rats with CIRI. This neuroprotective effect is mediated by multiple synergistic mechanisms, including the upregulation of tight junction proteins and the regulation of the AMPK/mTOR signaling pathway. Collectively, the findings of the present study suggest that DEX represents a promising potential agent for the clinical treatment of CIRI-associated BBB impairment.
Lv et al. (Wed,) studied this question.