Effects of repetitive transcranial magnetic stimulation on spasticity and BDNF-TrkB signaling pathway in rats with spinal cord injury
Objective:To investigate the effects of repetitive transcranial magnetic stimulation(rTMS)on spasticity in rats with spinal cord injury(SCI)and explore the relationship between the effect of rTMS on spasticity and the signaling pathway of BDNF-TrkB.Method:This study was divided into three parts:A,B and C.There were 18,30 and 15 female SD rats in each part,respectively,and a total of 63 SD rats.Rats in Part A and Part B were randomly divided into Sham group,SCI group and SCI+rTMS group.Rats in Part C were randomly divided into SCI group,SCI+rT-MS group,and SCI+rTMS+K252a group.One week after the successful SCI modeling,rTMS treatment groups were given a 4-week intervention.In Part A,H reflex(H-max/M-max ratio)was used to evaluate the spasticity,and BBB score was used to evaluate the motor function every week.In Part B,Western Blot and immunofluorescence were used to detect the expressions of BDNF,TrkB and KCC2 in cortex,the adjacent parts of damage and lumbosacral spinal cord after the experiment.One week after SCI modeling,K252a was used to block the BDNF-TrkB signaling pathway in the SCI+rTMS+K252a group.During 4 weeks of rTMS treatment,BBB score was used to evaluate the hind limb motor function of the rats every week.After experi-ment,Western Blot was used to detect the expression of KCC2.Result:①Part A:BBB scores in the SCI+rTMS group were significantly higher than those in SCI group dur-ing 2-5 weeks after SCI(P<0.05).At the 5th week after SCI,Hmax/Mmax in the SCI+rTMS group was signifi-cantly lower than that in the SCI group(P<0.05),there was no significant difference in RDD between the two groups(P>0.05).②Part B:Western Blot results showed that 5 weeks after SCI,the expressions of BDNF,TrkB and KCC2 in the cortex,adjacent to the spinal cord injury and lumbosacral spinal cord in the SCI+rTMS group were significantly increased compared with the SCI group(P<0.05).③Part C:During 2-5 weeks after SCI,BBB scores in the SCI+rTMS+K252a group were significantly lower than the SCI+rTMS group(P<0.05).Western Blot results showed that at the 5th week after SCI,the expression level of KCC2 in all parts in the SCI+rTMS+K252a group was significantly lower than the SCI+rTMS group(P<0.05).Conclusion:rTMS can relieve spasticity and improve motor function of SCI rats,which is related to the in-crease of BDNF,TrkB and KCC2.The mechanism of rTMS alleviating spasticity may be related to the BDNF-TrkB-KCC2 signaling pathway.
spinal cord injuryspasticityrepeated transcranial magnetic stimulationbrain-derived neurotrophic factor