Effect And Significance Of Dexamethasone On BDNF,TrkB And KCC2 Of Cerebellar Flocculus During Vestibular Compensation

Objective:To investigate the effect and significance of dexamethasone(DXM)on the expression of BDNF,TrkB and KCC2 in rat flocculus during central compensation after peripheral vestibular injury.Methods:The SD rats were randomly divided into five groups:normal saline group(negative control group),AA group(positive control group),low-dose DXM group,high-dose DXM group and DXM antagonist group.The rat model of vestibular injury was established by injection of arsanilic acid(AA)into the unilateral tympanum,and meanwhile,DXM was injected intraperitoneally in low and high dose DXM groups and RU486(DXM antagonist)was injected subcutaneously into the neck and back in DXM antagonist group for three consecutive days.On the fourth day of the experiment,posturo-locomotor functions of rats were observed.The positive rate of air righting reflex,contact righting reflex time and nystagmus frequency in the first 15 seconds after head fixation were recorded.The expression levels of BDNF,TrkB and KCC2 in rats' flocculus were detected by Western-blot,immunohistochemistry and reverse transcription-quantitative polymerase chain reaction assay and one-way analysis of variance(One-way ANOVA)was performed by Prism 8 statistical software,P<0.05 indicated that the difference was statistically significant.Results:In terms of behavior,compared with normal saline group,AA group had more severe vestibular dysfunction,lower positive rate of righting reflex,longer contact righting reflex time and more spontaneous nystagmus.The above-mentioned performance of low-dose and high-dose DXM groups were better than that of AA group,in which the improvement of high-dose group was more obvious,and the performance of rats in DXM antagonistic group was worse than that in high-dose DXM group,the difference between groups was statistically significant(P<0.05).In terms of molecular expression,the protein and mRNA expressions of BDNF,TrkB and KCC2 in the ipsilateral side of AA group were significantly lower than those in the control side(P<0.05),and the difference was statistically significant(P<0.05).Compared with AA group,the protein and mRNA expression of BDNF,TrkB and KCC2 in the flocculus of low dose DXM group and high dose DXM group were increased in turn,and the high dose DXM group increased more significantly,and the differences between groups were statistically significant(P<0.05).However,the protein and mRNA expression of BDNF,TrkB and KCC2 in the treated side of DXM antagonist group were significantly lower than those in DXM group(P<0.05).Conclusion:Intratympanic injection of AA may cause damage to the peripheral vestibular function of rats;the down-regulation of BDNF-TrkB signal expression in flocculus is involved in the vestibular dysfunction induced by AA;DXM acts on GR and activates the BDNF-TrkB signal of flocculus,and upregulates KCC2,which may be one of its ways to promote vestibular central compensation.