Activity-dependent plasticity and spinal cord stimulation for motor recovery following spinal cord injury

Samejima, Soshi; Henderson, Richard; Pradarelli, Jared; Mondello, Sarah E.; Moritz, Chet T.

doi:10.1016/j.expneurol.2022.114178

Cited by 17 publications

(12 citation statements)

References 210 publications

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“…After all, maladaptive neural activity was allowed to develop unchecked and to chronify naturally, resulting in a 'worst case scenario' for plasticity-promoting interventions. And whereas preclinical and clinical studies have repeatedly demonstrated the ability of motor-dominant circuits below a lesion to beneficially and durably reorganize (25)(26)(27)(28)(29)(30)(31)(32), neural transmission in spinal pain pathways has been comparatively difficult to shape. Indeed, interventions explicitly designed to promote functionally-relevant neural plasticity as well as those that attempt to pharmacologically rebalance spinal excitability have been met with variable and generally nominal successespecially when initiated after establishment of the neuropathic pain state (33,34).…”

Section: Discussionmentioning

confidence: 99%

Motor-targeted spinal stimulation promotes concurrent rebalancing of pathologic nociceptive transmission in chronic spinal cord injury

Bandres

Gomes²,

McPherson

2023

Preprint

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Electrical stimulation of spinal networks below a spinal cord injury (SCI) is a promising approach to restore functions compromised by inadequate excitatory neural drive. The most translationally successful examples are paradigms intended to increase neural transmission in weakened yet spared motor pathways and spinal motor networks rendered dormant after being severed from their inputs by lesion. Less well understood is whether spinal stimulation is also capable of reducing neural transmission in pathways made pathologically overactive by SCI. Debilitating spasms, spasticity, and neuropathic pain are all common manifestations of hyperexcitable spinal responses to sensory feedback. But whereas spasms and spasticity can often be managed pharmacologically, SCI-related neuropathic pain is notoriously medically refractory. Interestingly, however, spinal stimulation is a clinically available option for ameliorating neuropathic pain arising from etiologies other than SCI, and it has traditionally been assumed to modulate sensorimotor networks overlapping with those engaged by spinal stimulation for motor rehabilitation. Thus, we reasoned that spinal stimulation intended to increase transmission in motor pathways may simultaneously reduce transmission in spinal pain pathways. Using a well-validated pre-clinical model of SCI that results in severe bilateral motor impairments and SCI-related neuropathic pain, we show that the responsiveness of neurons integral to the development and persistence of the neuropathic pain state can be enduringly reduced by motor-targeted spinal stimulation while preserving spinal responses to non-painrelated sensory feedback. These results suggest that spinal stimulation paradigms could be intentionally designed to afford multi-modal therapeutic benefits, directly addressing the diverse, intersectional rehabilitation goals of people living with SCI.

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Section: Discussionmentioning

confidence: 99%

Motor-targeted spinal stimulation promotes concurrent rebalancing of pathologic nociceptive transmission in chronic spinal cord injury

Bandres

Gomes²,

McPherson

2023

Preprint

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“…For instance, a number of surfacing studies have explored the utility of deep brain stimulation for focal targeting of midbrain structures implicated in treatment-resistant depression [36][37][38], however sweeping conclusions remain illgeneralizable in the TBI patient population [39]. Hofer and Schwab further reviewed the therapeutic benefits afforded by electrical stimulation for spinal cord injury patients years after the initial injury event [40], owed to previously described activity-dependent restoration of residual brain and spinal cord networks [41].…”

Section: Repetitive Transcranial Magnetic Stimulationmentioning

confidence: 99%

Neurostimulation for Traumatic Brain Injury: Emerging Innovation

Diaz¹,

Root²,

Beneke³

et al. 2023

OBM Neurobiol

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Traumatic brain injury (TBI) is a significant source of brain deficit and death among neurosurgical patients, with limited prospects for functional recovery in the cases of moderate-to-severe injury. Until now, the relevant body of literature on TBI intervention has focused on first-line, invasive treatment options (namely craniectomy and hematoma evacuation) with underwhelming focus on non-invasive therapies following surgical stabilization. Recent advances in our understanding of the impaired brain have encouraged deeper investigation of neurostimulation strategies, owed largely to its demonstrated livening of damaged neural circuitry and capacity to stabilize erratic network activity. The objective of the present study is to provide a scoping review of new knowledge in neurostimulation published in the PubMed, Scopus, and Google Scholar databases from inception to November 2022. We critically assess and appraise the available data on primary neurostimulation delivery techniques, with marked emphasis on restorative opportunities for accessory neurostimulation in the interdisciplinary care of moderate-to-severe TBI (msTBI) patients. These data identify two primary future directions: 1) to relate obtained gain-of-function outcomes to hemodynamic and histological changes and 2) to develop a clearer understanding of neurostimulation efficacy, when combined with pharmacologic interventions or other modulatory techniques, for complex brain insult.

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“…The mechanisms for neural plasticity after SCI and how to enhance that plasticity to improve rehabilitation are still being elucidated. The increased inflammation may blunt the potential for neuroplasticity 118–121 . Gut dysbiosis post‐SCF could also impact important molecules involved in neuroplasticity after SCI, such as BDNF and other neurotrophic factors 122–126 .…”

Section: Spinal Cord Injurymentioning

confidence: 99%

“…The increased inflammation may blunt the potential for neuroplasticity. [118][119][120][121] Gut dysbiosis post-SCF could also impact important molecules involved in neuroplasticity after SCI, such as BDNF and other neurotrophic factors. [122][123][124][125][126] The intestinal microbiome modulates BDNF messenger RNA affecting the capacity for long-term potentiation in the hippocampus.…”

Section: Neuronal Recovery and Gut Dysbiosismentioning

confidence: 99%

Gut microbiome and neurosurgery: Implications for treatment

Willman

Reddy

et al. 2022

Clinical and Translational Dis

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Introduction: The aim of this review is to summarize the current understanding of the gut-brain axis (GBA), its impact on neurosurgery, and its implications for future treatment. Background: An abundance of research has established the existence of a collection of pathways between the gut microbiome and the central nervous system (CNS), commonly known as the GBA. Complicating this relationship, the gut microbiome bacterial diversity appears to change with age, antibiotic exposure and a number of external and internal factors. Methods: In this paper, we present the current understanding of the key protective and deleterious roles the gut microbiome plays in the pathogenesis of several common neurosurgical concerns. Results: Specifically, we examine how spinal cord injury, traumatic brain injury and stroke may cause gut microbial dysbiosis. Furthermore, this link appears to be bidirectional as gut dysbiosis contributes to secondary CNS injury in each of these ailment settings. This toxic cycle may be broken, and the future secondary damage rescued by timely, therapeutic, gut microbiome modification. In addition, a robust gut microbiome appears to improve outcomes in brain tumour treatment. There are several primary routes by which microbiome dysbiosis may be ameliorated, including faecal microbiota transplant, oral probiotics, bacteriophages, genetic modification of gut microbiota and vagus nerve stimulation. Conclusion: The GBA represents an important component of patient care in the field of neurosurgery. Future research may illuminate ideal methods of therapeutic microbiome modulation in distinct pathogenic settings.

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Activity-dependent plasticity and spinal cord stimulation for motor recovery following spinal cord injury

Cited by 17 publications

References 210 publications

Motor-targeted spinal stimulation promotes concurrent rebalancing of pathologic nociceptive transmission in chronic spinal cord injury

Motor-targeted spinal stimulation promotes concurrent rebalancing of pathologic nociceptive transmission in chronic spinal cord injury

Neurostimulation for Traumatic Brain Injury: Emerging Innovation

Gut microbiome and neurosurgery: Implications for treatment

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