Background:Neuronal structure is disrupted after spinal cord injury(SCl),causing functional impairment.The effectiveness of exercise therapy(ET)in clinical settings for nerve remodeling post-SCI and its underlying mec...Background:Neuronal structure is disrupted after spinal cord injury(SCl),causing functional impairment.The effectiveness of exercise therapy(ET)in clinical settings for nerve remodeling post-SCI and its underlying mechanisms remain unclear.This study aims to explore the effects and related mechanisms of ET on nerve remodeling in SCI rats.Methods:We randomly assigned rats to various groups:sham-operated group,sham-operated+ET,SCI alone,SCI+H89,SCI+ET,and SCI+ET+H89.Techniques including motor-evoked potential(MEP),video capture and analysis,the Basso-Beattie-Bresnahan(BBB)scale,western blotting,transmission electron microscopy,hematoxylin and eosin staining,Nissl staining,glycine silver staining,immunofluorescence,and Golgi staining were utilized to assess signal conduction capabilities,neurological deficits,hindlimb performance,protein expression levels,neuron ultrastructure,and tissue morphology.H89-an inhibitor that targets the protein kinase A(PKA)/cAMP response element-binding(CREB)signaling pathway-was employed to investigate molecular mechanisms.Results:This study found that ET can reduce neuronal damage in rats with SCl,protect residual tissue,promote the remodeling of motor neurons,neurofilaments,dendrites/axons,synapses,and myelin sheaths,reorganize neural circuits,and promote motor function recovery.In terms of mechanism,ET mainly works by mediating the PKA/CREB signaling pathway in neurons.Conclusions:Our findings indicated that:(1)ET counteracted the H89-induced suppression of the PKA/CREB signaling pathway following SCl;(2)ET significantly alleviated neuronal injury and improved motor dysfunction;(3)ET facilitated neuronal regeneration by mediating the PKA/CREB signaling pathway;(4)ET enhanced synaptic and dendritic spine plasticity,as well as myelin sheath remodeling,post-SCI through the PKA/CREB signaling pathway.展开更多
基金supported by National Natural Science Foundation of China(No.82302856,No.82271629 and No.81873376)China Postdoctoral Science Foundation under Grant Number 2024M762443+3 种基金Priority-Funded Postdoctoral Research Project,Zhejiang Province(ZJ2024133)Postdoctoral Fellowshiprogram of CPSF under Grant Number Grant Number GZC20241252Zhejiang Provincial Natural Science Foundation of China(No.LQ21H170003)Science Technology Bureau of Wenzhou funded project(No.Y20210164).
文摘Background:Neuronal structure is disrupted after spinal cord injury(SCl),causing functional impairment.The effectiveness of exercise therapy(ET)in clinical settings for nerve remodeling post-SCI and its underlying mechanisms remain unclear.This study aims to explore the effects and related mechanisms of ET on nerve remodeling in SCI rats.Methods:We randomly assigned rats to various groups:sham-operated group,sham-operated+ET,SCI alone,SCI+H89,SCI+ET,and SCI+ET+H89.Techniques including motor-evoked potential(MEP),video capture and analysis,the Basso-Beattie-Bresnahan(BBB)scale,western blotting,transmission electron microscopy,hematoxylin and eosin staining,Nissl staining,glycine silver staining,immunofluorescence,and Golgi staining were utilized to assess signal conduction capabilities,neurological deficits,hindlimb performance,protein expression levels,neuron ultrastructure,and tissue morphology.H89-an inhibitor that targets the protein kinase A(PKA)/cAMP response element-binding(CREB)signaling pathway-was employed to investigate molecular mechanisms.Results:This study found that ET can reduce neuronal damage in rats with SCl,protect residual tissue,promote the remodeling of motor neurons,neurofilaments,dendrites/axons,synapses,and myelin sheaths,reorganize neural circuits,and promote motor function recovery.In terms of mechanism,ET mainly works by mediating the PKA/CREB signaling pathway in neurons.Conclusions:Our findings indicated that:(1)ET counteracted the H89-induced suppression of the PKA/CREB signaling pathway following SCl;(2)ET significantly alleviated neuronal injury and improved motor dysfunction;(3)ET facilitated neuronal regeneration by mediating the PKA/CREB signaling pathway;(4)ET enhanced synaptic and dendritic spine plasticity,as well as myelin sheath remodeling,post-SCI through the PKA/CREB signaling pathway.
