The Effects Of Exercise Training On Spasticity Of Rat After Spinal Cord Injury And The Mechanism Implicated

Objective:To investigate the effect of exercise training on spasticity of the rat after spinal cord injury and to explore the mechanism of exercise training to relieve spasticity.Methods:The female SD rats were randomly classified into three groups:sham operated group(sham group),SCI control group(SCI-Sed group)and SCI treadmill training group(SCI-TT group).The SCI-TT group received exercise intervention with body weight support treadmill training.The spastic rat model after spinal cord injury(SCI)was induced by modified Allen’s,each group dynamically observed BBB scale,Ashworth scale and H reflex(including Hmax/Mmax ratio and Rate dependent depression ratio).The expression of Brain derived neurotrophic factor(BDNF),Tyrosine protein kinase B(TrkB),cAMP-response element binding protein(CREB),phosphorylated cAMP-response element binding protein(pCREB),Glutamic acid decarboxylase 65(GAD65),Glutamic acid decarboxylase 67(GAD67),γ-aminobutyric acid receptor B(GABA_B receptor),potassium-chloride cotransporter-2(KCC2)in injured spinal cord was examined by immunohistochemistry and western blot at the 5th week post injury.Results:(1)The behavior of sham operation group didn’t change.From the first day to fifth week after the operation,the BBB values of SCI-Sed group and SCI-TT group both increased,and each group showed statistically significant in the scales at different time after the operation(P<0.05).At the 2nd-5th week,the BBB values of SCI-TT group were higher than SCI-Sed group,and the differences between the 2groups were statistical significant(P<0.05).Ashworth values increased about one week after the operation in SCI-Sed group and SCI-TT group,and gradually aggravated afterwards.About 5 weeks after the operation,spasticity was somewhat alleviated.the Ashworth values was statistical significant at different time after the operation in each group(P<0.05).At the 3rd-5th week,the Ashworth values of SCI-Sed group were higher than those of SCI-TT group,and the differences showed statistically significant(P<0.05).(2)The H reflex of sham operation group didn’t change.The Hmax/Mmax ratio and RDD ratio increased about one week after the operation in SCI-Sed group and SCI-TT group,and gradually aggravated afterwards.About 5 weeks after the operation,the ratio was somewhat decreased.At the 3rd-5th week,the Hmax/Mmax ratio of SCI-Sed group were higher than those of SCI-TT group,and the differences showed statistically significant(P<0.05).At the third and fifth weeks,the RDD ratio of SCI-Sed group were higher than those of SCI-TT group,and the differences showed statistically significant(P<0.05).(3)Immunohistochemistry and western blot results showed that there were significant differences in the BDNF and TrkB expression among 3 groups(P<0.05).Furthermore,compared with the sham operation group,the BDNF and TrkB expression upregulated in the other 2 group,compared with the SCI-Sed group,the BDNF and TrkB expression of the SCI-TT group upregulated(P<0.05),but lower than sham operation group(P<0.05).Meanwhile,there were significant differences in the pCREB and activiationg of CREB among 3 groups.Compared with the SCI-Sed group,the pCREB and activiationg of CREB of the SCI-TT group upregulated(P<0.05)。In addition,there were significant differences in the GAD65、GAD67、GABA_B receptor and KCC2 expression among 3 groups(P<0.05).Furthermore,compared with the sham operation group,the GAD65、GAD67、GABA_B receptor and KCC2 expression downregulated in the other 2 group,compared with the SCI-Sed group,the GAD65、GAD67、GABA_B receptor and KCC2 expression of the SCI-TT group upregulated(P<0.05),but lower than sham operation group(P<0.05).Conclusion:The occurrence of spasticity after SCI may be related to the decrease of GAD65,GAD67,GABA_B receptor and KCC2 expression in the distal segment of spinal cord injury.Exercise training can promote the recovery of motor function in SCI rats and relieve spasm effectively.It may be related to the induction of BDNF/TrkB synthesis,the increase of pCREB and activiationg of CREB,the promotion of GAD65/67,and the enhancement of GABA_B receptor and KCC2 expression.