The Effect And Mechanism Of Microglial Activation In Post-stroke Spasticity

Objectives:Spasticity is one of the most common symptoms in the cerebral or spinal disorders.It is also the major cause of disability of neurological diseases and the hot spot in the rehabilitation researches.Recent studies have shown that activation of microglia after neurological disease contributes to excitability of the hyperexcitability of spinal neurons,is considered a possible mechanism at the basis of spasticity.The aim of this study was to investigate the correlation betw,een microglia activation in the spinal cord neurons loop and cerebral spasticity,thus further discuss the role of microglia activation in pathophysiological mechanism of spasticity and provide a theoretical basis for the clinical treatment of spasticity.Methods:Rat cerebral spasticiy intracerebral hemorrhage model was established by stereotaxic injection of collagenase in right striatum.Electromyography and behavioral tests were performed on 1,3,7,14 days after cerebral hemorrhage and 14 dyas after the microglia inhibition.Three electrophysiology parameters including H wave latency,H wave amplitude and H/M of fifth toe muscle were observed to identify those that changed in spasticity.Behavioral tests including modified Neurological deficit score(mNSS)and Cylinder test were performed to investigate the motor function after spasticity.The expression of OX42 in transverse sections of the brain,neck segment,thoracic segment and lumbar spinal cord were detected by immunohistochemical method to evaluate the activation and proliferation of microglia.Results:1.electrophysiological parameters1.1 Unilateral cerebral spasticity ICH rats displayed a significant conralateral decrease in H latency on day 3 and day 7(P<0.05);A contralateral increase in H amplitude on day 3,day 7 and day 14(P<0.05);A contralateral increase in H/M ratio on day 3(P<0.05);compared control group,ICH group and MG group,a decrease in contralateral hindlimb H latency(P<0.05)1.2 It cues both ICH group and MG group existed the phenomenon of increased excitatory activity in spinal cord neurons.The contralateral H latency of MG group was higher than that of ICH group on day 7 and day 14.(P<0.05).2.Behavioural evaluation2.1 mNSS:compared control group,an increase score on day 1,day 3,day 7 and day 14 in ICH group.(P<0.05)2.2 mNSS:compared control group,an increase score on day 1,day 3,day 7 and day 14 in MG group.(P<0.05)It cues that two group existed obvious nerve function defect.2.3 Compared with ICH group,a decrease of mNSS score on day 3 and day 7(P<0.05)in MG group.It showed that the nerve function defect was recovered in MG group.2.4 Cylinder test:a decrease in contralateral forelimb usage in ICH group detected on day 3?day 7 and day 14 compared with control group.(P<0.05)2.5 Cylinder test:a decrease in contralateral forelimb usage in MG group detected on day 3,day 7 and day 14 compared with control group.It cues that two group existed the reduction ot the use rate on the affected forelimb.But it showed no significant on cylinder test compared with spasticity ICH rats on 3 time poionts.(P<0.05)3.Elevated expressions of OX423.1 It can be observed in white matters at brain as well as cervical and lumbar segments of spinal cord in cerebral spasticity ICH rats on day 3,7,14.3.2 Compared with MG gruop and ICH group on day 14,the number of OX42 positive cells in the brain white matter in MG group decreased(P<0.05)3.3 The number of positive cells of microglia OX42 in the cervical and lumbar segments of the white matter was decreased in the MG group and ICH group on day 14,the difference was statistically significant.(P<0.05)4.Correlation4.1 The H amplitude of the fifth toe of the affected side was positively correlated with the number of activated microglia in the white matter of the brain(r=0.733,P<0.01).4.2 There was a negative correlation between the latency of H and the activation of microglia in the cervical spinal cord(r=-0.819,P<0.01).4.3 Cylinder Test was negatively correlated with the activation of microglia in the cervical spinal cord(r=-0.745,P<0.01).Conclusion:1.The striatum cerebral hemorrhage model can successfully induce brain-derived spasticity.The motor function showed that the use rate of the forelimb on the affected side was reduced,and the H reflex showed an increased excitability of the spinal cord.2.The increased expression of activated microglial cells was found in the white matter of brain and spinal cord in the spasticity model after ICH injury.The expression of brain derived spasticity may be related to the activation and proliferation of microglia in the central nervous system.