Effects of Edaravone Dexborneol on Neural Function and BDNF-AKT-CREB Signaling Pathway in Ischemic Stroke Rats
Objective:To investigate the effect of edaravone dexborneol(EDDE)on neurological func-tion in rats with cerebral ischemic stroke(CIS),and to preliminarily explore the possible mechanism of BDNF(brain-derived neurotrophic factor)-AKT-CREB(cAMP response element binding protein)signaling path-way.Methods:Rats were randomly divided into five groups:sham operation group(sham group),CIS model group(CIS group),EDDE low dose group(EDDE-L group),EDDE high dose group(EDDE-H group),and nimodipine group;neural function was assessed by mNSS scoring method,and the area of cerebral infarc-tion was detected by 2,3,5-triphenyltetrazolium chloride(TTC)staining in the rat,and the area of ni The pathological damage of rat brain tissue was observed,and the interleukin-1β(IL-1β),interleukin-6(IL-6),superoxide dismutase(SOD),malondialdehyde(MDA)content,BDNF mRNA,AKT mRNA,CREB mRNA,and BDNF,AKT,CREB protein expression of brain tissue were also detected.Results:Compared with the sham group,the neurological function score,cerebral infarction area,apoptosis rate and the contents of IL-1β,IL-6,and MDA in the CIS group were significantly increased,while the expressions of SOD,BD-NF mRNA,AKT mRNACREB mRNA,BDNF protein,AKT protein,CREB protein were significantly de-creased(P<0.05).At the same time the number of cells in the cerebral cortex decreases,vacuoles are more numerous and nuclei appear to be consolidated.Compared with the CIS group,the neurological function scores,cerebral infarct area,apoptosis rate,and the contents of IL-1β,IL-6,and MDA were significantly reduced in the EDDE-L,EDDE-H,and nimodipine groups,whereas the contents of SOD,the BDNF mR-NA,AKT mRNA,CREB mRNA,and the expression of BDNF protein,AKT protein,and CREB protein were all significantly increased(P<0.05),and the cellular structure of the cerebral cortex was also relatively in-tact;among them,the effect was more obvious in the EDDE-H and nimodipine groups(P<0.05).Conclu-sion:EDDE may reduce the area of cerebral infarction and improve the neurological impairment in CIS rats by activating the BDNF-AKT-CREB pathway,inhibiting the expression of inflammatory factors,and reducing the level of oxidative stress.
Edaravone dexborneolBDNF-AKT-CREB signaling pathwayIschemic strokeNeurological function
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