Multimodal rehabilitation promotes axonal sprouting and functional recovery in a murine model of spinal cord injury (SCI)

Wang, Yunhang; Luo, Haodong; Liu, Yuan; Yang, Chen; Yin, Ying; Tan, Botao

doi:10.1016/j.neulet.2022.137029

Cited by 3 publications

(2 citation statements)

References 41 publications

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“…Based on our data, combining treadmill training with OPN strongly activated mTOR signaling in the right sensorimotor cortex. Additionally, our previous studies reported that treadmill training promotes CST axon sprouting, close connectivity of sprouted axons with neurons, and the reforming of synaptic connectivity [ 62 , 67 ]. Therefore, the sprouting and regeneration of the left side CST (injured) axons may be another reason that promotes functional recovery.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin enhances the effect of treadmill training and promotes functional recovery after spinal cord injury

Wang,

Su,

Zhong

et al. 2023

Mol Biomed

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In this study, we examined the combined impact of osteopontin (OPN) and treadmill training on mice with spinal cord injury (SCI). OPN was overexpressed by injecting AAV9-SPP1-GFP into the sensorimotor cortex, followed by a left incomplete C5 crush injury two weeks later. Mice (Ex or Ex + OPN group) were trained at 50% maximum running speed for 8 weeks. To analyze the effects, we used biotinylated dextran amine (BDA) for tracing the corticospinal tract (CST) and performed Western blotting and immunohistochemical methods to assess the activation of the mammalian target of rapamycin (mTOR). We also examined axonal regeneration and conducted behavioral tests to measure functional recovery. The results demonstrated that treadmill training promoted the expression of neurotrophic factors such as brain-derived neurotrophic factor (BNDF) and insulin-like growth factor I (IGF-1) and activated mTOR signaling. OPN amplified the effect of treadmill training on activating mTOR signaling indicated by upregulated phosphorylation of ribosomal protein S6 kinase (S6). The combination of OPN and exercise further promoted functional recovery and facilitated limited CST axonal regeneration which did not occur with treadmill training and OPN treatment alone. These findings indicate that OPN enhances the effects of treadmill training in the treatment of SCI and offer new therapeutic insights for spinal cord injury.

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Section: Discussionmentioning

confidence: 99%

Osteopontin enhances the effect of treadmill training and promotes functional recovery after spinal cord injury

Wang,

Su,

Zhong

et al. 2023

Mol Biomed

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“…First, the limited axon regrowth observed following SCI may be insufficient for regaining pre-injury levels of motor control. Other strategies (e.g., NSC grafts [26][27][28] , rehabilitation 32,33 , chondroitinase treatment with peripheral nerve grafts 34,35 ) may need to be incorporated to further enhance motor recovery. A second possibility is that other circuits in addition to the CST, such as ascending sensory fibers, may also need restoration to regain full functionality.…”

Section: Discussionmentioning

confidence: 99%

Forelimb motor recovery by modulating extrinsic and intrinsic signaling as well as neuronal activity after the cervical spinal cord injury

Takatani,

Fujita,

Imai

et al. 2024

Preprint

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SUMMARYSingular strategies for promoting axon regeneration and motor recovery after spinal cord injury (SCI) have been attempted with limited success. Here, we propose the combinatorial approach of deleting extrinsic and intrinsic factors paired with neural stimulation, will enhance adaptive axonal growth and motor recovery after SCI. We previously showed the deletion ofRhoAandPtenin corticospinal neurons inhibits axon dieback and promotes axon sprouting after lumbar SCI. Here, we examined the effects ofRhoA;Ptendeletion coupled with neural stimulation after cervical SCI. This combinatorial approach promoted more boutons on injured corticospinal neurons in the spinal cord compared to soleRhoA;Ptendeletion. AlthoughRhoA;Ptendeletion does not promote motor recovery in the forelimb after SCI, stimulating corticospinal neurons in those mice results in partial motor recovery. These results demonstrate that a combinatorial approach that pairs genetic modifications with neuronal stimulation can promote axon sprouting and motor recovery following SCI.

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Low-Dose LPS Modulates Microglia/Macrophages Phenotypic Transformation to Amplify Rehabilitation Effects in Chronic Spinal Cord Injured (CSCI) Mice

Zhong,

He,

Zhao

et al. 2024

Mol Neurobiol

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Multimodal rehabilitation promotes axonal sprouting and functional recovery in a murine model of spinal cord injury (SCI)

Cited by 3 publications

References 41 publications

Osteopontin enhances the effect of treadmill training and promotes functional recovery after spinal cord injury

Osteopontin enhances the effect of treadmill training and promotes functional recovery after spinal cord injury

Forelimb motor recovery by modulating extrinsic and intrinsic signaling as well as neuronal activity after the cervical spinal cord injury

Low-Dose LPS Modulates Microglia/Macrophages Phenotypic Transformation to Amplify Rehabilitation Effects in Chronic Spinal Cord Injured (CSCI) Mice

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