Corticospinal circuit neuroplasticity may involve silent synapses: Implications for functional recovery facilitated by neuromodulation after spinal cord injury

Chen, Mingcong; Chen, Zuxin; Xiao, Xiao; Zhou, Libing; Fu, Rao; Jiang, Xian; Pang, Mao; Xia, Jianxun

doi:10.1016/j.ibneur.2022.08.005

Cited by 2 publications

(1 citation statement)

References 127 publications

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“…Currently, there are many studies supporting a potential role for post-synaptic plasticity in encouraging axonal regeneration and recovery. Notably, recent studies have shown that following SCI, electrical stimulation can significantly increase the growth and branching of axons via upregulation of axon growth-and regeneration-promoting genes and factors, which also contributes to induction of Hebbian www.nature.com/scientificreports/ plasticity 46,47 . Furthermore, previously "silent" (NDMA-only) synapses have been found to undergo activation and reorganization in the face of electrical stimulation, which has been proposed to be a potential mechanism for rejuvenating neural pathways via encouragement of post-injury synaptic plasticity and axonal regrowth 46 .…”

Section: Discussionmentioning

confidence: 99%

Exposure to an enriched environment modulates the synaptic vesicle cycle in a mouse spinal cord injury model

Yoo,

Shin,

Lim

et al. 2024

Sci Rep

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Spinal cord injury (SCI) leads to motor and sensory impairment below the site of injury, thereby necessitating rehabilitation. An enriched environment (EE) increases social interaction and locomotor activity in a mouse model, similar to human rehabilitation. However, the impact of EE on presynaptic plasticity in gene expression levels remains unclear. Hence, this study aimed to investigate the therapeutic potential of EE in an SCI mouse model. Mice with spinal cord contusion were divided into two groups: those housed in standard cages (control) and those in EE conditions (EE). Each group was housed separately for either 2- or 8-weeks post-injury, after which RNA sequencing was performed and compared to a sham group (receiving only a dorsal laminectomy). The synaptic vesicle cycle (SVC) pathway and related genes showed significant downregulation after SCI at both time points. Subsequently, we investigated whether exposure to EE for 2- and 8-weeks post-SCI could modulate the SVC pathway and its related genes. Notably, exposure to EE for 8 weeks resulted in a marked reversal effect of SVC-related gene expression, along with stimulation of axon regeneration and mitigation of locomotor activity loss. Thus, prolonged exposure to EE increased presynaptic activity, fostering axon regeneration and functional improvement by modulating the SVC in the SCI mouse model. These findings suggest that EE exposure proves effective in inducing activity-dependent plasticity, offering a promising therapeutic approach akin to rehabilitation training in patients with SCI.

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Section: Discussionmentioning

confidence: 99%

Exposure to an enriched environment modulates the synaptic vesicle cycle in a mouse spinal cord injury model

Yoo,

Shin,

Lim

et al. 2024

Sci Rep

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DBS in the restoration of motor functional recovery following spinal cord injury

Li,

Qu,

et al. 2024

Front. Neurol.

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The landscape of therapeutic deep brain stimulation (DBS) for locomotor function recovery is rapidly evolving. This review provides an overview of electrical neuromodulation effects on spinal cord injury (SCI), focusing on DBS for motor functional recovery in human and animal models. We highlight research providing insight into underlying cellular and molecular mechanisms. A literature review via Web of Science and PubMed databases from 1990 to May 29, 2024, reveals a growing body of evidence for therapeutic DBS in SCI recovery. Advances in techniques like optogenetics and whole-brain tractogram have helped elucidate DBS mechanisms. Neuronal targets sites for SCI functional recovery include the mesencephalic locomotor region (MLR), cuneiform nucleus (CNF), and nucleus raphe magnus (NRG), with pedunculopontine nucleus (PPN), periaqueductal gray (PAG), and nucleus ventroposterolateral thalami (VPL) for post-injury functional recovery treatment. Radiologically guided DBS optimization and combination therapy with classical rehabilitation have become an effective therapeutic method, though ongoing interventional trials are needed to enhance understanding and validate DBS efficacy in SCI. On the pre-clinical front, standardization of pre-clinical approaches are essential to enhance the quality of evidence on DBS safety and efficacy. Mapping brain targets and optimizing DBS protocols, aided by combined DBS and medical imaging, are critical endeavors. Overall, DBS holds promise for neurological and functional recovery after SCI, akin to other electrical stimulation approaches.

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Corticospinal circuit neuroplasticity may involve silent synapses: Implications for functional recovery facilitated by neuromodulation after spinal cord injury

Cited by 2 publications

References 127 publications

Exposure to an enriched environment modulates the synaptic vesicle cycle in a mouse spinal cord injury model

Exposure to an enriched environment modulates the synaptic vesicle cycle in a mouse spinal cord injury model

DBS in the restoration of motor functional recovery following spinal cord injury

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