Elsevier eBooks, Год журнала: 2022, Номер unknown, С. 35 - 67
Опубликована: Дек. 2, 2022
Язык: Английский
Nature Communications, Год журнала: 2022, Номер 13(1)
Опубликована: Сен. 26, 2022
Abstract After spinal cord injury, tissue distal to the lesion contains undamaged cells that could support or augment recovery. Targeting these requires a clearer understanding of their injury responses and capacity for repair. Here, we use single nucleus RNA sequencing profile how each cell type in lumbar changes after thoracic mice. We present an atlas dynamic across dozens types acute, subacute, chronically injured cord. Using this resource, find rare neurons express signature regeneration response including major population represent spinocerebellar projection neurons. characterize anatomically observed axonal sparing, outgrowth, remodeling cerebellum. Together, work provides key resource studying cellular uncovers spontaneous plasticity neurons, uncovering potential candidate targeted therapy.
Язык: Английский
Процитировано
66
North American Spine Society Journal (NASSJ), Год журнала: 2023, Номер 15, С. 100235 - 100235
Опубликована: Июнь 8, 2023
Spinal cord injury (SCI) is a debilitating condition with significant personal, societal, and economic burden. The highest proportion of traumatic injuries occur at the cervical level, which results in severe sensorimotor autonomic deficits. Following initial physical trauma associated injuries, secondary pro-inflammatory, excitotoxic, ischemic cascades are initiated further contributing to neuronal glial cell death. Additionally, emerging evidence has begun reveal that spinal interneurons undergo subtype specific neuroplastic circuit rearrangements weeks months following SCI, or hindering functional recovery. current therapeutic guidelines standards care for SCI patients include early surgery, hemodynamic regulation, rehabilitation. preclinical work ongoing clinical trials have exploring neuroregenerative strategies utilizing endogenous neural stem/progenitor cells, stem transplantation, combinatorial approaches, direct reprogramming. This review will focus on cellular non-cellular regenerative therapies an overview available strategies, role plasticity, exciting research avenues enhancing tissue repair SCI.
Язык: Английский
Процитировано
14
Current Opinion in Neurobiology, Год журнала: 2023, Номер 82, С. 102763 - 102763
Опубликована: Авг. 21, 2023
Язык: Английский
Процитировано
11
Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(15)
Опубликована: Апрель 8, 2025
Various strategies targeting spinal locomotor circuitry have been associated with functional improvements after cord injury (SCI). However, the neuronal populations mediating beneficial effects remain largely unknown. Using a combination therapy in mouse model of complete SCI, we show that virally delivered brain-derived neurotrophic factor (BDNF) (AAV-BDNF) activates hindlimb stepping and causes hyperreflexia, whereas submotor threshold epidural stimulation (ES) reduces BDNF-induced hyperreflexia. Given their role gating proprioceptive afferents as potential convergence point BDNF ES, hypothesized an enhanced excitability inhibitory RORβ neurons would be improvements. Ex vivo slice recordings from mice range hyperreflexia scores revealed was related to outcome post-SCI. Mice poor function SCI had less excitable neurons, but similar between uninjured “best stepping” groups. Further, chemogenetic activation reduced improved stepping, ES. Our findings identify target population limit enhance SCI.
Язык: Английский
Процитировано
0
The Journal of Physiology, Год журнала: 2025, Номер unknown
Опубликована: Май 11, 2025
Abstract Locomotor behaviours are performed by organisms throughout life, despite developmental changes in cellular properties, neural connectivity and biomechanics. The basic rhythmic activity the central nervous system underlying locomotion is considered to be generated via a complex interplay between network intrinsic properties. Within mature mammalian spinal locomotor circuitry, we have yet determine which properties of interneurons (INs) critical rhythmogenesis how they change during development. Here, combined whole cell patch clamp recordings, immunohistochemistry RNAscope targeting lumbar Shox2 INs mice, known involved rhythm generation. Our goal was postnatal expression voltage‐sensitive conductances, addition respective ion channels, INs. We show that subsets display persistent inward currents, M‐type potassium slow afterhyperpolarization T‐type calcium enhanced with age. By contrast, hyperpolarization‐activated A‐type currents were either found low prevalence neonatal, juvenile, adult or did not developmentally change. become more electrophysiologically diverse juvenile ages, when behaviour becomes weight‐bearing. Computational modelling used simulate reproduce electrophysiological experiments for representative make predictions regarding interactions experimentally recorded conductances bursting behaviour. results suggest shift magnitude rhythmogenic ionic corresponding channels may important image Key points locomotor‐related neurons contribute shaping maintaining activity. (INs), similar many other components well‐characterized neonatal mouse. Electrophysiological recordings reveal express ‘rhythmogenic properties’, including afterhyperpolarization, as well channels/RNA. Hierarchical clustering demonstrates seen related emergence types, largely defined strong current expression. data gain diversity age, from mice employ
Язык: Английский
Процитировано
0
Cell Reports, Год журнала: 2022, Номер 41(4), С. 111535 - 111535
Опубликована: Окт. 1, 2022
Mechanisms underlying spontaneous locomotor recovery after spinal cord injury (SCI) remain unclear. Using adult zebrafish with complete SCI, we show that V2a interneurons regrow their axon to bridge the lesioned segments in a subclass-specific and chronological order. Early reestablishment of unitary high-rhythm circuit is driven merely by axon-regrown fast interneurons. Later, reestablished intraspinal de novo organized into modular design slow rostral lesion, selectively driving caudal V2a/motor neurons neurons, respectively. This orderly circuitry determines stepwise restoration repertoire recapitulates developmental processes. progress can be interrupted ablation calretinin, module-related protein, accelerated physical training. These findings suggest promotion regrowth propriospinal establishment circuits underpin effectiveness training patients SCI.
Язык: Английский
Процитировано
13
Biology, Год журнала: 2021, Номер 10(10), С. 976 - 976
Опубликована: Сен. 28, 2021
Neuroplasticity is a robust mechanism by which the central nervous system attempts to adapt structural or chemical disruption of functional connections between neurons. Mechanical damage from spinal cord injury potentiates via neuroinflammation and can cause aberrant changes in neural circuitry known as maladaptive plasticity. Together, these alterations greatly diminish function quality life. This review discusses contemporary efforts harness neuroplasticity through rehabilitation neuromodulation restore with focus on motor recovery following cervical injury. Background information general mechanisms plasticity long-term potentiation system, most well studied learning memory fields, will be reviewed. Spontaneous both during natural outlined provide baseline builds. Previous research has focused impact descending commands driving However, this focuses influence physical therapy primary afferent input interneuron modulation within cord. Finally, future directions into previously untargeted populations are presented.
Язык: Английский
Процитировано
17
Communications Biology, Год журнала: 2023, Номер 6(1)
Опубликована: Май 19, 2023
Abstract Neural progenitor cell (NPC) transplantation is a promising therapeutic strategy for replacing lost neurons following spinal cord injury (SCI). However, how graft cellular composition influences regeneration and synaptogenesis of host axon populations, or recovery motor sensory functions after SCI, poorly understood. We transplanted developmentally-restricted NPCs, isolated from E11.5-E13.5 mouse embryos, into sites adult SCI analyzed outgrowth, composition, regeneration, behavior. Earlier-stage grafts exhibited greater enrichment ventral interneurons Group-Z interneurons, enhanced 5-HT + regeneration. Later-stage were enriched late-born dorsal horn interneuronal subtypes Group-N supported more extensive CGRP ingrowth, exacerbated thermal hypersensitivity. Locomotor function was not affected by any type NPC graft. These findings showcase the role in determining anatomical functional outcomes SCI.
Язык: Английский
Процитировано
6
Cells, Год журнала: 2024, Номер 13(8), С. 652 - 652
Опубликована: Апрель 9, 2024
The differential expression of transcription factors during embryonic development has been selected as the main feature to define specific subclasses spinal interneurons. However, recent studies based on single-cell RNA sequencing and transcriptomic experiments suggest that this approach might not be appropriate in adult cord, where interneurons show overlapping profiles, especially ventral region. This constitutes a major challenge for identification direct targeting populations could involved locomotor recovery after traumatic cord injury adults. Current experimental therapies, including electrical stimulation, training, pharmacological treatments, or cell implantation, have resulted improvements behavior rely modulation activity connectivity located surroundings lesion core formation detour circuits. very few publications clarify identity these cells. In work, we review premotor were able create new intraspinal circuits different kinds injury, highlighting difficulties encountered by researchers, classify populations.
Язык: Английский
Процитировано
2
Frontiers in Systems Neuroscience, Год журнала: 2022, Номер 16
Опубликована: Март 3, 2022
In most vertebrates, posture and locomotion are achieved by a biomechanical apparatus whose effectors symmetrically positioned around the main body axis. Logically, motor commands to these intrinsically adapted such anatomical symmetry, underlying sensory-motor neural networks correspondingly arranged during central nervous system (CNS) development. However, many developmental and/or life accidents may alter organization acutely generate asymmetries in operation that often at least partially compensated for over time. First, we briefly present basic of posturo-locomotor vertebrates. Next, review some aspects plasticity is implemented response unilateral injury or asymmetrical sensory deprivation order substantially restore symmetry control functions. Data finally discussed context CNS structure-function relationship.
Язык: Английский
Процитировано
9