The Functional Role of Spinal Interneurons Following Traumatic Spinal Cord Injury

Zavvarian, Mohammad-Masoud; Hong, James; Fehlings, Michael G.

doi:10.3389/fncel.2020.00127

Cited by 40 publications

(25 citation statements)

References 117 publications

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“…For the formation of neuronal relays, propriospinal neurons and interneurons might be ideal as these neurons serve as natural “relays” in the intact spinal cord [ 85 ]. In preclinical studies, spinal interneurons and propriospinal neurons can serve as relays for injured circuits and promote functional recovery in incomplete spinal cord injuries [ 86 , 87 ].…”

Section: Neural Stem Cell Transplants As a Relay For Spinal Cord Connectivitymentioning

confidence: 99%

Neural Stem Cells: Promoting Axonal Regeneration and Spinal Cord Connectivity

Freria

Niekerk

Blesch

et al. 2021

Cells

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Spinal cord injury (SCI) leads to irreversible functional impairment caused by neuronal loss and the disruption of neuronal connections across the injury site. While several experimental strategies have been used to minimize tissue damage and to enhance axonal growth and regeneration, the corticospinal projection, which is the most important voluntary motor system in humans, remains largely refractory to regenerative therapeutic interventions. To date, one of the most promising pre-clinical therapeutic strategies has been neural stem cell (NSC) therapy for SCI. Over the last decade we have found that host axons regenerate into spinal NSC grafts placed into sites of SCI. These regenerating axons form synapses with the graft, and the graft in turn extends very large numbers of new axons from the injury site over long distances into the distal spinal cord. Here we discuss the pathophysiology of SCI that makes the spinal cord refractory to spontaneous regeneration, the most recent findings of neural stem cell therapy for SCI, how it has impacted motor systems including the corticospinal tract and the implications for sensory feedback.

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Section: Neural Stem Cell Transplants As a Relay For Spinal Cord Connectivitymentioning

confidence: 99%

Neural Stem Cells: Promoting Axonal Regeneration and Spinal Cord Connectivity

Freria

Niekerk

Blesch

et al. 2021

Cells

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“…The latter regulate motor activity by GABAergic signaling, but also releasing Glycine, important in spinal cord presynaptic inhibition. Spinal cord interneurons contribution into injury induced neuroplasticity is documented; however, this was not yet directly linked to PGC-1α activity and its role in this process still needs to be explained [ 74 ].…”

Section: Role Of Pgc-1α In Different Types Of Neuronal Cells In the Nervous Systemmentioning

confidence: 99%

Covering the Role of PGC-1α in the Nervous System

Kuczynska

Metin

Liput

et al. 2021

Cells

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The peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a well-known transcriptional coactivator involved in mitochondrial biogenesis. PGC-1α is implicated in the pathophysiology of many neurodegenerative disorders; therefore, a deep understanding of its functioning in the central nervous system may lead to the development of new therapeutic strategies. The central nervous system (CNS)-specific isoforms of PGC-1α have been recently identified, and many functions of PGC-1α are assigned to the particular cell types of the central nervous system. In the mice CNS, deficiency of PGC-1α disturbed viability and functioning of interneurons and dopaminergic neurons, followed by alterations in inhibitory signaling and behavioral dysfunction. Furthermore, in the ALS rodent model, PGC-1α protects upper motoneurons from neurodegeneration. PGC-1α is engaged in the generation of neuromuscular junctions by lower motoneurons, protection of photoreceptors, and reduction in oxidative stress in sensory neurons. Furthermore, in the glial cells, PGC-1α is essential for the maturation and proliferation of astrocytes, myelination by oligodendrocytes, and mitophagy and autophagy of microglia. PGC-1α is also necessary for synaptogenesis in the developing brain and the generation and maintenance of synapses in postnatal life. This review provides an outlook of recent studies on the role of PGC-1α in various cells in the central nervous system.

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“…combined with further sources of excitation (116) and potentially contributing to subsequent motor recovery (27). Interneurons may also activate dormant relay circuits to restore sensorimotor function (191) but are involved in both adaptive and maladaptive anatomical and functional plasticity after SCI, and there is growing interest in how this may contribute to respiratory function (192).…”

Section: Other Ees Substratesmentioning

confidence: 99%

Electrical epidural stimulation of the cervical spinal cord: implications for spinal respiratory neuroplasticity after spinal cord injury

Malone

Nosacka

Nash

et al. 2021

Journal of Neurophysiology

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Traumatic cervical spinal cord injury (cSCI) can lead to damage of bulbospinal pathways to the respiratory motor nuclei and consequent life-threatening respiratory insufficiency due to respiratory muscle paralysis/paresis. Reports of electrical epidural stimulation (EES) of the lumbosacral spinal cord to enable locomotor function after SCI are encouraging, with some evidence of facilitating neural plasticity. Here, we detail the development and success of EES in recovering locomotor function with consideration of stimulation parameters and safety measures to develop effective EES protocols. EES is just beginning to be applied in other motor, sensory, and autonomic systems; however, there has only been moderate success in preclinical studies aimed at improving breathing function after cSCI. Thus, we explore rationale for applying EES to the cervical spinal cord, targeting the phrenic motor nucleus for the restoration of breathing. We also suggest cellular/molecular mechanisms by which EES may induce respiratory plasticity including a brief examination of sex-related differences in these mechanisms. Finally, we suggest more attention be paid to the effects of specific electrical parameters that have been used in the development of EES protocols and how that can impact the safety and efficacy for those receiving this therapy. Ultimately, we aim to inform readers about the potential benefits of EES in the phrenic motor system and encourage future studies in this area.

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The Functional Role of Spinal Interneurons Following Traumatic Spinal Cord Injury

Cited by 40 publications

References 117 publications

Neural Stem Cells: Promoting Axonal Regeneration and Spinal Cord Connectivity

Neural Stem Cells: Promoting Axonal Regeneration and Spinal Cord Connectivity

Covering the Role of PGC-1α in the Nervous System

Electrical epidural stimulation of the cervical spinal cord: implications for spinal respiratory neuroplasticity after spinal cord injury

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