Dexmedetomidine attenuates cerebral ischemia-reperfusion injury in rats by inhibiting the JNK pathway

BACKGROUND: Cerebral ischemic reperfusion injury (CI/RI) is a common cerebrovascular disease with high morbidity and disability that threatens human health. This study was conducted to explore the effects of dexmedetomidine (Dex) on the c-Jun N-terminal kinase (JNK) pathway in CI/RI, and to provide a theoretical basis for the recovery of brain function after cerebral ischemia. METHODS: Sprague Dawley (SD) rats (n=24) were randomly divided into Sham, Sham + Dex, Sham + yohimbine (Yoh) + Dex, Sham + SP600125, ischemic reperfusion (I/R), I/R + Dex, I/R + Yoh + Dex, and I/R + SP600125 groups, and a focal cerebral ischemia reperfusion rat model was established by linear thrombus. The neurological deficit score and infarct volume were measured. Wet/dry weight ratios were used to measure brain water content, and cerebral infarct volume was determined by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The cellular distribution of p-JNK and cleaved caspase-3 were examined using immunofluorescent staining (IF) and the total JNK and p-JNK were determined by Western blotting (WB). RESULTS: Compared with the Sham group, the rats in I/R, I/R + Dex, I/R + Yoh + Dex, and I/R + SP600125 groups developed hemiparesis of the left forelimb at different levels with a higher neurological deficit score, brain water content, infarct volume, and markedly upregulated expression of cleaved caspase-3, p-JNK (P<0.05). Compared with the I/R group, the neurological deficit score, brain water content, infarct volume, and expression of cleaved caspase-3, p-JNK were markedly decreased in I/R + Dex, I/R + Yoh + Dex, and I/R + SP600125 groups (P<0.05), and compared with the I/R + Dex group, the neurological deficit score, brain water content, infarct volume, and expression of cleaved caspase-3, p-JNK were markedly increased in the I/R + Yoh + Dex group (P<0.05). Double immunofluorescence staining showed there was a strong colocalization between p-JNK and the astroglial marker GFAP. CONCLUSIONS: The JNK signaling pathway is involved in CI/RI. Inhibition of the JNK pathway blocked caspase-3 activation which can decrease CI/RI. Dex can alleviate cerebral CI/RI in rats by increasing α2-adrenergic receptor and blocking JNK phosphorylation and activation of caspase-3.