The effect of edaravone on the inflammasome NLRP3 and blood brain barrier associated protein after embolic stroke in rat / 医学研究生学报

ABSTRACT

ObjectiveIn cerebral ischemia, free radicals form in large quantities and activate the inflammasome nod-like recepter protein 3(NLRP3), thereby exacerbating brain damage. Edaravone has the effect of scavenging free radicals, but the relationgship between its neuroprotective effect and inflammasome NLRP3 has not been reported. To study the neuroprotective effects of edaravone on inflammasome NLRP3 and associated protein of the blood-brain barrier against cerebral ischemia injury.Methods60 male Sprague-Dawley rats were randomly divided into Sham group, cerebral embolism group and edaravone group, respectively. Rat thromboembolic MCAO models were established and edaravone (3mg/kg) was intravenous injected immediately after occlusion and 4 hours after occlusion. In the sham group, cervical blood vessels were separated only, and no embolus was injected. At 24 hours after thrombi injected, mNSS score was used to evaluate neurological function deficits. Brain infarct volume was estimated by TTC staining. The expression of inflammasome NLRP3, occludin and ZO-1 was detected by Western blot. Immunohistochemistry was used to measure IgG leakage.ResultsThe mNSS score and infarct volume of cerebral embolism group at 24 hours after stroke were significantly higher than Sham group (P<0.05). The expression of inflammasome NLRP3 in the brain increased (P<0.05), occludin and ZO-1 blood brain barrier associated protein decreased (P<0.05), and IgG leakage increased. But compared with cerebral embolism group, the mNSS score（4.50±2.12 vs 6.50±1.35, P<0.05）and infarct volume （19.29±11.92 vs 29.99±7.56, P<0.05）decreased when treated with edaravone. Edaravone treatment significantly attenuated inflammasome NLRP3 expression in cerebral ischemic area (0.97±0.47 vs 1.58±0.86, P<0.05), degradation of BBB components (occludin, ZO-1) (1.04±0.19 vs 0.53±0.09, 0.66±0.05 vs 0.30±0.04,P<0.05) and IgG leakage decreased.ConclusionInflammasome NLRP3 play an important role in acute cerebral ischemia injury. Edaravone may provide neuroprotection by inhibiting expression of inflammasome NLRP3 and degradation of associated protein of blood brain barrier.