Edaravone Alleviates Delayed Neuronal Death And Long-dated Cognitive Dysfunction Of Hippocampus After Transient Focal Ischemia In Wistar Rat Brains

Objective:Edaravone is currently being used in acute ischemic stroke both in clinical and experimental research as a potent free radical scavenger. However, current research mainly focuses on Ischemic core and penumbra surrounding of acute cerebrovascular diseases, later nerve injury and long term cognitive impairment occurred in the region away from ischemic site such as hippocampus has not been reported until now. In this part of the study, we will explore the effect of edaravone on delayed neuronal death and long-dated cognitive dysfunction of hippocampus after transient focal ischemia in Wistar rat brains.Materials and Methods:Wistar rats were divided into sham group (surgery was performed on rats but without artery occlusion, n=28), vehicle group (rats were treated with saline solution after the middle cerebral artery occlusion (MCAO), n=72) and edaravone-treated group (3mg/kg of edaravone was administered intravenously immediately and 30 min after reperfusion, n=72). The model of middle cerebral artery occlusion was established. Nissl and TUNEL staining were performed to observe neuronal loss and apoptosis in hippocampus CA1 at 3,7,30 days after reperfusion. Morris water maze test was performed to evaluate learning and memory function of rats at 30 day after reperfusion.Results:Nissl and TUNEL staining revealed a restricted loss of neuron and apoptosis in the pyramidal layer of the ipsilateral hippocampus at 3,7 and 30 days after MCAO (1 h). But in the edaravone-treated group, the loss of neuron and apoptosis were significantly reduced at all time points tested compared to the vehicle group. The vehicle group displayed a significantly longer escape latency and less time in the target quadrant compared to the sham group, suggesting that ischemia/reperfusion strongly induces learning dysfunction. Edaravone-treated group behaved completely different compared to the vehicle group, Furthermore, results demonstrated that the edaravone-treated rats spent significantly more time in the target quadrant when the hidden platforms were removed on the last day of training. These results indicated that administration of edaravone alleviated rat long-term cognitive impairment caused by MCAO and improved their spatial learning and memory effectively.Conclusion:This part of the study showed that edaravone reduced hippocampal delayed neuronal death and Protected long-term cognitive function after reperfusion of Middle cerebral artery occlusion. Objective:The mechanism of hippocampal delayed neuronal death (DND) has rarely been reported. In our study we found that Edaravone alleviates delayed neuronal death in rat hippocampus after focal cerebral ischemia. In this part of study we will further research the mechanism of edaravone on delayed neuronal death.Materials and Methods:The model of middle cerebral artery occlusion was established. MDA and SOD in the ipsilateral hippocampus were detected at 3,7,30 days after MCAO. Protein and mRNA expression of IL-1βand TNF-a at 3,7,30 days after MCAO were evaluated by ELISA and RT-PCR. TUNEL and GFAP staining in the ipsilateral hippocampus were performed at 3,7,30 days following MCAO. Western blot was used for analysis of GFAP expression at 3,7,30 days following MCAO.Results:Our findings suggested that Ischemia group showed significantly increased MDA, decreased SOD activity, markedly increased IL-1(3 and TNF-a protein and mRNA expression levels in the ipsilateral hippocampus compared with the sham group at days 3,7 after MCAO. Edaravone markedly decreased MDA levels and increased SOD levels. In addition, edaravone reduced the levels of inflammatory cytokines IL-1βand TNF-a expression at 3d and 7d after reperfusion; Edaravone, also suppressed GFAP proliferation at days 3,7 and 30 after reperfusion.Conclusion:the consensus emerging from this body of data indicated that edaravone exerts a later neuroprotective effect to hippocampus through its ability to inhibit inflammation, suppression of astrocyte activation and scavenging free radicals in stroke events.