Dexmedetomidine attenuates cerebral ischemia-reperfusion injury by inhibiting c-Jun N-terminal kinase and p38 pathway in rats

Objective To establish cerebral ischemia reperfusion injury induced by middle cerebral artery occlusion (MCAO), and investigate whether the effect of dexmedetomidine (Dex) on the cerebral ischemia reperfusion (I/R) injury is connected with c-Jun N-terminal kinase (JNK) and p38 pathways. Methods Fifty-four adult male SD rats, weighing 240-280 g, were randomly divided into three groups: sham group, I/R group and Dex group. I/R group and Dex group were subjected to cerebral ischemia, which was induced by the MCAO. Dex group was administered with Dex when ischemia began through the tail vein at 3 μg/kg for 5 min, then at the speed of 6 μg/(kg·h) dose of continuous pumping for 2 h. Sham group and I/R group were given equal volume of normal saline at the same time points. After 90 min ischemia and 24 h reperfusion, animals were evaluated for motor-deficits, then sacrificed for further analysis. The wet minus dry weight method was applied for the analysis of brain water content, staining with 2% triphenyltetrazolium chloride (TTC) to measure infarct areas, immunofluorescence to observe p-JNK, p-p38 and cleaved cysteinyl aspartate-specific protease (Caspase)-3 in brain tissue, and Western blotting to detect the protein expression of p-JNK and p-p38. Results As compared with the I/R group, the neurological deficit score, the brain water content and the cerebral infarct size were significantly decreased in Dex group [2.86±0.45 vs. 2.16±0.63, (85.23±1.19)% vs. (79.16±1.50)%, (28.53±1.68)% vs. (20.09±1.62)%, F=136.500, P=0.000; F=162.777, P=0.000; F=707.707, P=0.000]. As compared with the I/R group, the number of cells expressing p-p38 (32.33±3.01 vs. 18.67±2.73, F=210.481, P=0.000), p-JNK (35.33±3.20 vs. 17.83±2.48, F=257.534, P=0.000) and cleaved Caspase-3 (51.50±3.62 vs. 33.00±3.58, F=346.888, P=0.000) was significantly redcued in Dex group. As compared with I/R group, the protein expression of p-p38 (1.38±0.11 vs. 2.08±0.19, F=190.834, P=0.000), p-JNK (0.77±0.06 vs. 1.31±0.08, F=514.456, P=0.000) was significantly decreased in Dex group. Conclusion Dex can attenuate cerebral I/R probably by inhibiting JNK and p38 phosphorylation, then decreasing the activation of Caspase-3. Key words: Dexmedetomidine; Cerebral ischemia; Repeffusion injury; Mitogen-activated protein kinases