Effects Of Repetitive Transcranial Magnetic Stimulation And Exercise Training On The Recovery Of Motor Function In A Rat Model Of Incomplete Spinal Cord Injury

Background: Spinal cord injury(SCI)is a neurological disorder,leading to severe and permanent motor and sensory dysfunction.After SCI,in some neural circuits plastic changes occur not only in the spinal cord but also in cortical structures.The key factor in promoting locomotion recovery may be the construction of plasticity both in the motor cortex and the spinal cord.Research have showed that exercise training and repetitive transcranial magnetic stimulation(rTMS)could promote neuroplasticity and functional recovery after SCI.Moreover,recent studies suggest that the combination of exercise training and rTMS may be more beneficial for functional recovery than monotherapy.However,the researches on the combination of exercise training and magnetic/electrical stimulation mainly focused on the local neural functional remodeling of the spinal cord,but do not involve the motor cortex.Objective: To investigate the effects of exercise training and rTMS on motor functional recovery,spinal reflex,motor cortical and spinal neuroplasticity in rats with incomplete SCI.Methods: Sixty rats with incomplete SCI induced by moderate T9 contusive SCI model were randomly allocated to five groups: Sham surgery(Intact),Sham rTMS without treadmill training(S-rTMS/Non-TT),Sham rTMS with TT(S-rTMS/TT),rTMS without TT(rTMS/Non-TT)and rTMS with TT(rTMS/TT).Interventions commenced 8 days after SCI and continued for 8 weeks.Outcomes studied were Basso,Beattie and Bresnahan(BBB)locomotor scale scores,grid walking test,H-reflex and biochemical analysis of the brain-derived neurotrophic factor(BDNF),synapsin I(SYN)and postsynaptic density protein-95(PSD-95)in the motor cortex and spinal cord.Results:(1)BBB scores: rTMS/TT group showed significantly higher BBB scores than those in the S-rTMS/Non-TT(P<0.01),S-rTMS/TT(P<0.05)and rTMS/Non-TT(P<0.05)groups.(2)Grid walking test: The number of foot drops in the rTMS/TT group was significantly less than that in the S-rTMS/Non-TT group(P<0.05).(3)H-reflex: The S-rTMS/Non-TT group showed significantly higher Hmax/Mmax than that in the Intact group(P<0.01);Hmax/Mmax in the rTMS/TT and rTMS/Non-TT groups were close to the level of the Intact group(P>0.05),and significantly lower than that in S-rTMS/Non-TT group(P<0.05).(4)The expressions of BDNF,SYN and PSD-95 in the motor cortex: a)The expressions of BDNF(Immunohistochemistry/Western Blot: P<0.05,P<0.05)and PSD-95(P<0.05,P<0.05)in the rTMS/TT group were significantly higher than those in the S-rTMS/TT group.The expressions of BDNF(P<0.05,P<0.05)and PSD-95(P<0.01,P<0.05)in the rTMS/Non-TT group were significantly higher than those in the S-rTMS/Non-TT group.b)No statistically significant difference was observed between the rTMS/TT and the rTMS/Non-TT groups.No statistically significant difference was observed between the S-rTMS/TT and the S-rTMS/Non-TT groups.c)Compared with the S-rTMS/Non-TT group,the expressions of BDNF(P<0.01,P<0.001),SYN(P<0.01,P<0.05)and PSD-95(P<0.001,P<0.001)were significantly increased in the rTMS/TT group.(5)The expressions of BDNF,SYN and PSD-95 in the spinal cord: a)The BDNF expression in the rTMS/TT group was significantly higher than that in rTMS/Non-TT group(P<0.001,P<0.001).The BDNF expression in the S-rTMS/TT group was significantly higher than that in the S-rTMS/Non-TT group(P<0.001,P<0.001).b)The BDNF expression in the rTMS/TT group was significantly higher than that in the S-rTMS/TT group(P<0.01,P<0.05).No statistically significant difference was observed between the rTMS/Non-TT and S-rTMS/Non-TT groups.c)Compared with S-rTMS/Non-TT group,rTMS/TT group not only significantly increased the BDNF expression(P<0.001,P<0.001),but also the expressions of synaptic plasticity markers SYN(P<0.01,P<0.05)and PSD-95(P<0.05,P<0.05).Conclusion: In a rat model of incomplete SCI,combined exercise training with rTMS effectively improved the motor function,inhibited H-reflex facilitation and promoted the adaptive neuroplasticity between the motor cortex and the spinal cord,which providing theoretical basis for SCI bimodal therapy.