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1.
Nature ; 611(7936): 540-547, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36352232

RESUMO

A spinal cord injury interrupts pathways from the brain and brainstem that project to the lumbar spinal cord, leading to paralysis. Here we show that spatiotemporal epidural electrical stimulation (EES) of the lumbar spinal cord1-3 applied during neurorehabilitation4,5 (EESREHAB) restored walking in nine individuals with chronic spinal cord injury. This recovery involved a reduction in neuronal activity in the lumbar spinal cord of humans during walking. We hypothesized that this unexpected reduction reflects activity-dependent selection of specific neuronal subpopulations that become essential for a patient to walk after spinal cord injury. To identify these putative neurons, we modelled the technological and therapeutic features underlying EESREHAB in mice. We applied single-nucleus RNA sequencing6-9 and spatial transcriptomics10,11 to the spinal cords of these mice to chart a spatially resolved molecular atlas of recovery from paralysis. We then employed cell type12,13 and spatial prioritization to identify the neurons involved in the recovery of walking. A single population of excitatory interneurons nested within intermediate laminae emerged. Although these neurons are not required for walking before spinal cord injury, we demonstrate that they are essential for the recovery of walking with EES following spinal cord injury. Augmenting the activity of these neurons phenocopied the recovery of walking enabled by EESREHAB, whereas ablating them prevented the recovery of walking that occurs spontaneously after moderate spinal cord injury. We thus identified a recovery-organizing neuronal subpopulation that is necessary and sufficient to regain walking after paralysis. Moreover, our methodology establishes a framework for using molecular cartography to identify the neurons that produce complex behaviours.


Assuntos
Neurônios , Paralisia , Traumatismos da Medula Espinal , Medula Espinal , Caminhada , Animais , Humanos , Camundongos , Neurônios/fisiologia , Paralisia/genética , Paralisia/fisiopatologia , Paralisia/terapia , Medula Espinal/citologia , Medula Espinal/fisiologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia , Caminhada/fisiologia , Estimulação Elétrica , Região Lombossacral/inervação , Reabilitação Neurológica , Análise de Sequência de RNA , Perfilação da Expressão Gênica
2.
JAMA Surg ; 157(11): 1024-1032, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36169962

RESUMO

Importance: The optimal clinical management of central cord syndrome (CCS) remains unclear; yet this is becoming an increasingly relevant public health problem in the face of an aging population. Objective: To provide a head-to-head comparison of the neurologic and functional outcomes of early (<24 hours) vs late (≥24 hours) surgical decompression for CCS. Design, Setting, and Participants: Patients who underwent surgery for CCS (lower extremity motor score [LEMS] - upper extremity motor score [UEMS] ≥ 5) were included in this propensity score-matched cohort study. Data were collected from December 1991 to March 2017, and the analysis was performed from March 2020 to January 2021. This study identified patients with CCS from 3 international multicenter studies with data on the timing of surgical decompression in spinal cord injury. Participants were included if they had a documented baseline neurologic examination performed within 14 days of injury. Participants were eligible if they underwent surgical decompression for CCS. Exposures: Early surgery was compared with late surgery. Main Outcomes and Measures: Propensity scores were calculated as the probability of undergoing early compared with late surgery using the logit method and adjusting for relevant confounders. Propensity score matching was performed in a 1:1 ratio by an optimal-matching technique. The primary end point was motor recovery (UEMS, LEMS, American Spinal Injury Association [ASIA] motor score [AMS]) at 1 year. Secondary end points were Functional Independence Measure (FIM) motor score and complete independence in each FIM motor domain at 1 year. Results: The final study cohort consisted of 186 patients with CCS. The early-surgery group included 93 patients (mean [SD] age, 47.8 [16.8] years; 66 male [71.0%]), and the late-surgery group included 93 patients (mean [SD] age, 48.0 [15.5] years; 75 male [80.6%]). Early surgical decompression resulted in significantly improved recovery in upper limb (mean difference [MD], 2.3; 95% CI, 0-4.5; P = .047), but not lower limb (MD, 1.1; 95% CI, -0.8 to 3.0; P = .30), motor function. In an a priori-planned subgroup analysis, outcomes were comparable with early or late decompressive surgery in patients with ASIA Impairment Scale (AIS) grade D injury. However, in patients with AIS grade C injury, early surgery resulted in significantly greater recovery in overall motor score (MD, 9.5; 95% CI, 0.5-18.4; P = .04), owing to gains in both upper and lower limb motor function. Conclusions and Relevance: This cohort study found early surgical decompression to be associated with improved recovery in upper limb motor function at 1 year in patients with CCS. Treatment paradigms for CCS should be redefined to encompass early surgical decompression as a neuroprotective therapy.


Assuntos
Síndrome Medular Central , Traumatismos da Medula Espinal , Humanos , Masculino , Idoso , Pessoa de Meia-Idade , Síndrome Medular Central/cirurgia , Estudos de Coortes , Descompressão Cirúrgica/métodos , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/cirurgia , Coluna Vertebral/cirurgia
3.
Biomater Adv ; 139: 212971, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35882128

RESUMO

Spinal cord injury (SCI) is a devastating condition resulting in loss of motor function. The pathology of SCI is multifaceted and involves a cascade of events, including neuroinflammation and neuronal degeneration at the epicenter, limiting repair process. We developed a supermacroporous, mechanically elastic, electro-conductive, graphene crosslinked collagen (Gr-Col) cryogels for the regeneration of the spinal cord post-injury. The effects of graphene in controlling astrocytes reactivity and microglia polarization are evaluated in spinal cord slice organotypic culture and rat spinal cord lateral hemisection model of SCI. In our work, the application of external electric stimulus results in the enhanced expression of neuronal markers in an organotypic culture. The implantation of Gr-Col cryogels in rat thoracic T9-T11 hemisection model demonstrates an improved functional recovery within 14 days post-injury (DPI), promoted myelination, and decreases the lesion volume at the injury site. Decrease in the expression of STAT3 in the implanted Gr-Col cryogels may be responsible for the decrease in astrocytes reactivity. Microglia cells within the implanted cryogels shows higher anti-inflammatory phenotype (M2) than inflammatory (M1) phenotype. The higher expression of mature axonal markers like ß-tubulin III, GAP43, doublecortin, and neurofilament 200 in the implanted Gr-Col cryogel confirms the axonal regeneration after 28 DPI. Gr-Col cryogels also modulate the production of ECM matrix, favouring the axonal regeneration. This study shows that Gr-Col cryogels decreases neuroinflammation and accelerate axonal regeneration.


Assuntos
Axônios , Colágeno , Criogéis , Grafite , Regeneração Nervosa , Doenças Neuroinflamatórias , Traumatismos da Medula Espinal , Animais , Axônios/fisiologia , Colágeno/uso terapêutico , Criogéis/uso terapêutico , Grafite/uso terapêutico , Doenças Neuroinflamatórias/fisiopatologia , Doenças Neuroinflamatórias/terapia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia
4.
J Neurosci ; 42(25): 5007-5020, 2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35589391

RESUMO

Consolidation of memory is believed to involve offline replay of neural activity. While amply demonstrated in rodents, evidence for replay in humans, particularly regarding motor memory, is less compelling. To determine whether replay occurs after motor learning, we sought to record from motor cortex during a novel motor task and subsequent overnight sleep. A 36-year-old man with tetraplegia secondary to cervical spinal cord injury enrolled in the ongoing BrainGate brain-computer interface pilot clinical trial had two 96-channel intracortical microelectrode arrays placed chronically into left precentral gyrus. Single- and multi-unit activity was recorded while he played a color/sound sequence matching memory game. Intended movements were decoded from motor cortical neuronal activity by a real-time steady-state Kalman filter that allowed the participant to control a neurally driven cursor on the screen. Intracortical neural activity from precentral gyrus and 2-lead scalp EEG were recorded overnight as he slept. When decoded using the same steady-state Kalman filter parameters, intracortical neural signals recorded overnight replayed the target sequence from the memory game at intervals throughout at a frequency significantly greater than expected by chance. Replay events occurred at speeds ranging from 1 to 4 times as fast as initial task execution and were most frequently observed during slow-wave sleep. These results demonstrate that recent visuomotor skill acquisition in humans may be accompanied by replay of the corresponding motor cortex neural activity during sleep.SIGNIFICANCE STATEMENT Within cortex, the acquisition of information is often followed by the offline recapitulation of specific sequences of neural firing. Replay of recent activity is enriched during sleep and may support the consolidation of learning and memory. Using an intracortical brain-computer interface, we recorded and decoded activity from motor cortex as a human research participant performed a novel motor task. By decoding neural activity throughout subsequent sleep, we find that neural sequences underlying the recently practiced motor task are repeated throughout the night, providing direct evidence of replay in human motor cortex during sleep. This approach, using an optimized brain-computer interface decoder to characterize neural activity during sleep, provides a framework for future studies exploring replay, learning, and memory.


Assuntos
Aprendizagem/fisiologia , Córtex Motor/fisiologia , Sono/fisiologia , Adulto , Interfaces Cérebro-Computador , Vértebras Cervicais , Eletroencefalografia/métodos , Humanos , Masculino , Projetos Piloto , Quadriplegia/etiologia , Quadriplegia/fisiopatologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/fisiopatologia
5.
Hum Exp Toxicol ; 41: 9603271211066587, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35243930

RESUMO

OBJECTIVE: To explore the effects of hypoxic preconditioning neural stem cell (P-NSC) transplantation on rats with spinal cord injury (SCI). METHODS: After identification, the NSCs were treated with hypoxic preconditioning. The NSCs migration was detected by Transwell method. RT-qPCR was used to detect the mRNA levels of HIF-1α, CXCR4 in NSC. The secretion of representative neurotrophic factors (VEGF, HGF, and BDNF) was checked by Western blot. Forty-six SCI rats were randomly divided into three experimental groups: SCI group (PBS injection, n = 10); N-NSC group (NSC atmospheric normoxic pretreatment injection, n = 18); and P-NSC group (NSC 's hypoxic preconditioning injection, n = 18). The sham operation group was also included (rats underwent laminectomy but not SCI, n = 10). The recovery of hindlimb motor function was evaluated by BBB score. The level of spinal cord inflammation (IL-1ß, TNF-α, and IL-6) was determined by ELISA. Western blot was used to detect the content of TMIGD1 and TMIGD3 in spinal cord. RESULTS: Compared with the N-NSC group, the number of NSC-passing membranes in the P-NSC group increased with the increase of the culture time (p < 0.05). Compared with N-NSC, P-NSC had higher levels of VEGF, HGF, and BDNF after 1 week of culture (p < 0.05). The BBB score of the P-NSC group was significantly higher than that of the N-NSC group at 7 and 28 days (p < 0.05). Compared with the SCI group, the levels of TNF-α, IL-1ß, and IL-6 were significantly reduced after NSC treatment, and the P-NSC group was lower than the N-NSC group (p < 0.05). Compared with the SCI group, the levels of TMIGD1 and TMIGD3 increased. Compared with the N-NSC group, and the levels of TMIGD1 and TMIGD3 increased in the P-NSC group (p < 0.05). CONCLUSION: P-NSC administration could improve SCI injury, and the levels of TMIGD1 and TMIGD3.


Assuntos
Membrana Celular/metabolismo , Movimento Celular/efeitos dos fármacos , Domínios de Imunoglobulina , Células-Tronco Neurais/transplante , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/cirurgia , Transplante de Células-Tronco/métodos , Animais , Hipóxia , Masculino , Ratos , Ratos Sprague-Dawley
6.
Dev Cell ; 57(4): 415-416, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35231422

RESUMO

The capacity for long-distance axon regeneration and functional recovery after spinal cord injury in the adult has long been thought to be a unique feature of certain non-mammalian vertebrates. However, in this issue of Developmental Cell, Nogueira-Rodrigues et al. report an astonishingly high regenerative ability in the spiny mouse.


Assuntos
Axônios , Traumatismos da Medula Espinal , Animais , Modelos Animais de Doenças , Regeneração Nervosa , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia
7.
Biochem Biophys Res Commun ; 598: 124-130, 2022 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-35158211

RESUMO

At present, there are no satisfactory therapeutic drugs for the functional recovery of spinal cord injury (SCI). We previously identified a novel peptide (OM-LV20) that accelerated the regeneration of injured skin tissues of mice and exerts neuroprotective effects against cerebral ischemia/reperfusion injury in rats. Here, the intraperitoneal injection of OM-LV20 (1 µg/kg) markedly improved motor function recovery in the hind limbs of rats with traumatic SCI, and further enhanced spinal cord repair. Administration of OM-LV20 increased the number of surviving neuron bodies, as well as the expression levels of brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB). In the acute stage of SCI, OM-LV20 treatment also increased superoxide dismutase and glutathione content but decreased the levels of malonaldehyde and nitric oxide. Thus, OM-LV20 significantly promoted structural and functional recovery of SCI in adult rats by increasing neuronal survival and BDNF and TrkB expression, and thereby regulating the balance of oxidative stress. Based on our knowledge, this research is the first report on the effects of amphibian-derived peptide on the recovery of SCI and our results highlight the potential of peptide OM-LV20 administration in the acceleration of the recovery of SCI.


Assuntos
Peptídeos/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/fisiopatologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Feminino , Ratos Sprague-Dawley , Receptor trkB/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Traumatismos da Medula Espinal/metabolismo
8.
Arch Phys Med Rehabil ; 103(7): 1387-1397, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35202581

RESUMO

OBJECTIVE: To describe the status of spinal cord stimulation (SCS) research for the improvement of motor, sensory, and autonomic function for individuals living with a spinal cord injury (SCI). DATA SOURCES: This scoping review identified original research published before March 31, 2021, via literature searches using MEDLINE, Embase, PubMed, Science Direct, Cumulative Index to Nursing and Allied Health, Sport Discus, and Web of Science, as well as a targeted search for well-known principal investigators. Search terms included permutations of "spinal cord stimulation," "epidural spinal cord stimulation," "transcutaneous spinal cord stimulation," "magnetic spinal cord stimulation," and "neuromodulation." STUDY SELECTION: Studies were included if they (1) were in English, (2) presented original research on humans living with a SCI, and (3) investigated at least 1 of the 3 forms of SCS. DATA EXTRACTION: Extracted data included authors, publication year, participant characteristics, purpose, study design, stimulation (device, location, parameters), primary outcomes, and adverse events. DATA SYNTHESIS: As a scoping review the extracted data were tabulated and presented descriptively. Themes and gaps in the literature were identified and reported. Of the 5754 articles screened, 103 articles were included (55 epidural, 36 transcutaneous, 12 magnetic). The primary research design was a case study or series with only a single randomized controlled trial. Motor recovery was the most common primary outcome for epidural and transcutaneous SCS studies, whereas bowel and bladder outcomes were most common for magnetic SCS studies. Seventy percent of the studies included 10 or fewer participants, and 18 articles documented at least 1 adverse event. Incomplete stimulation parameter descriptions were noted across many studies. No articles mentioned direct engagement of consumers or advocacy groups. CONCLUSIONS: This review identified a need for more robust study designs, larger sample sizes, comparative studies, improved reporting of stimulation parameters, adverse event data, and alignment of outcomes with the priorities of the community with SCI.


Assuntos
Traumatismos da Medula Espinal/terapia , Estimulação da Medula Espinal , Humanos , Traumatismos da Medula Espinal/fisiopatologia
9.
Toxins (Basel) ; 14(1)2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35051024

RESUMO

Botulinum neurotoxin type A (BoNT-A) injection and augmentation enterocystoplasty (AE) are alternative and effective management strategies for neurogenic detrusor overactivity (NDO) refractory to pharmacotherapy. A great majority of patients with spinal cord injury (SCI) may, however, prefer BoNT-A injections to AE, due to the less invasive characteristics. In this study we evaluated the influence of various video-urodynamic study (VUDS) parameters in SCI patients who continuously received repeat BoNT-A detrusor injections or switched to AE to improve their bladder conditions. We compared the changes in the urodynamic parameters before and after each mode of treatment. In this retrospective study, all SCI patients with refractory NDO who had received at least one BoNT-A injection were enrolled. VUDS was performed before and after both BoNT-A injection and AE. All of the urodynamic parameters of the storage and micturition-including the bladder capacity of every sensation, maximal flow rate (Qmax), post-voiding residual volume, detrusor pressure at Qmax, and bladder contractility index-were recorded. A total of 126 patients, including 46 women and 80 men, with a mean age of 41.8 ± 13.1 years, were recruited for this study. All of the patients receiving either BoNT-A injection or AE had a statistically significant increase of bladder capacity at every time-point during filling and a decrease in detrusor pressure at Qmax during voiding. Patients who switched from BoNT-A to AE had greater improvements in their urodynamic parameters when compared with those who continued with BoNT-A injections. Accordingly, SCI patients receiving BoNT-A injections but experiencing few improvements in their urodynamic parameters should consider switching to AE to achieve a better storage function and bladder capacity.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Procedimentos Cirúrgicos do Sistema Digestório/estatística & dados numéricos , Bexiga Urinaria Neurogênica/tratamento farmacológico , Bexiga Urinária Hiperativa/tratamento farmacológico , Urodinâmica , Procedimentos Cirúrgicos Urológicos/estatística & dados numéricos , Adulto , Anastomose Cirúrgica/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Traumatismos da Medula Espinal/fisiopatologia
10.
Dev Cell ; 57(4): 440-450.e7, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-34986324

RESUMO

Regeneration of adult mammalian central nervous system (CNS) axons is abortive, resulting in inability to recover function after CNS lesion, including spinal cord injury (SCI). Here, we show that the spiny mouse (Acomys) is an exception to other mammals, being capable of spontaneous and fast restoration of function after severe SCI, re-establishing hind limb coordination. Remarkably, Acomys assembles a scarless pro-regenerative tissue at the injury site, providing a unique structural continuity of the initial spinal cord geometry. The Acomys SCI site shows robust axon regeneration of multiple tracts, synapse formation, and electrophysiological signal propagation. Transcriptomic analysis of the spinal cord following transcriptome reconstruction revealed that Acomys rewires glycosylation biosynthetic pathways, culminating in a specific pro-regenerative proteoglycan signature at SCI site. Our work uncovers that a glycosylation switch is critical for axon regeneration after SCI and identifies ß3gnt7, a crucial enzyme of keratan sulfate biosynthesis, as an enhancer of axon growth.


Assuntos
Axônios/fisiologia , Regeneração Nervosa/fisiologia , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/patologia , Animais , Axônios/patologia , Modelos Animais de Doenças , Glicosilação , Camundongos , Medula Espinal/fisiologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Coluna Vertebral/fisiopatologia
11.
Behav Brain Res ; 422: 113731, 2022 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-34979221

RESUMO

Animal models of cervical spinal cord injury (SCI) have frequently utilized partial transection injuries to evaluate plasticity promoting treatments such as rehabilitation training of skilled reaching and grasping tasks. Though highly useful for studying the effects of cutting specific spinal tracts that are important for skilled forelimb motor function, cervical partial-transection SCI-models underappreciate the extensive spread of most human SCIs, thus offering poor predictability for the clinical setting. Conversely, moderate cervical contusion SCI models targeting the spinal tracts important for skilled reaching and grasping can better replicate the increased size of most human SCIs and are often considered more clinically relevant. However, it is unknown whether animals with moderate cervical contusion SCIs that damage key spinal motor tracts can train in skilled reaching and grasping tasks. In this study, we quantify the impact of injury size and distribution on recovery in a skilled motor task called the single pellet reaching, grasping and retrieval (SPRGR) task in rats with cervical unilateral contusion injuries (UCs), and compare to rats with a partial transection SCIs (i.e., dorsolateral quadrant transection; DLQ). We found that UCs damage key tracts important for performing skilled motor tasks, similar to DLQs, but UCs also produce more extensive grey matter damage and more ventral white matter damage than DLQs. We also compared forelimb functionality at 1, 3, and 5 weeks of rehabilitative motor training between trained and untrained rats and found a more severe drop in SPRGR performance than in DLQ SCIs. Nevertheless, despite more severe injuries and initially low SPRGR performance, rehabilitative training for contusion animals resulted in significant improvements in SPRGR performance and proportionally more recovery than DLQ rats. Our findings show that rehabilitative motor training can facilitate considerable amounts of motor recovery despite extensive spinal cord damage, especially grey matter damage, thus supporting the use of contusion or compression SCI models and showing that ventral grey and white matter damage are not necessarily detrimental to recovery after training.


Assuntos
Medula Cervical/lesões , Terapia por Exercício , Membro Anterior/fisiopatologia , Destreza Motora/fisiologia , Reabilitação Neurológica , Condicionamento Físico Animal/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/reabilitação , Animais , Comportamento Animal/fisiologia , Contusões/fisiopatologia , Contusões/reabilitação , Modelos Animais de Doenças , Ratos
12.
PLoS One ; 17(1): e0262755, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35085322

RESUMO

Chronic spinal cord injury (SCI) is a highly debilitating and recalcitrant disease with limited treatment options. Although various stem cell types have shown some clinical efficacy for injury repair they have not for SCI. Hair-follicle-associated pluripotent (HAP) stem cells have been shown to differentiate into neurons, Schwan cells, beating cardiomyocytes and many other type of cells, and have effectively regenerated acute spinal cord injury in mouse models. In the present report, HAP stem cells from C57BL/6J mice, encapsulated in polyvinylidene fluoride membranes (PFM), were implanted into the severed thoracic spinal cord of C57BL/6J or athymic nude mice in the early chronic phase. After implantation, HAP stem cells differentiated to neurons, astrocytes and oligodendrocytes in the regenerated thoracic spinal cord of C57BL/6J and nude mice. Quantitative motor function analysis, with the Basso Mouse Scale for Locomotion (BMS) score, demonstrated a significant functional improvement in the HAP-stem-cell-implanted mice, compared to non-implanted mice. HAP stem cells have critical advantages over other stem cells: they do not develop teratomas; do not loose differentiation ability when cryopreserved and thus are bankable; are autologous, readily obtained from anyone; and do not require genetic manipulation. HAP stem cells therefore have greater clinical potential for SCI repair than induced pluripotent stem cells (iPSCs), neuronal stem cells (NSCs)/neural progenitor cells (NPCs) or embryonic stem cells (ESCs). The present report demonstrates future clinical potential of HAP-stem-cell repair of chronic spinal cord injury, currently a recalcitrant disease.


Assuntos
Folículo Piloso/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes/citologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia , Regeneração da Medula Espinal/fisiologia , Animais , Diferenciação Celular/fisiologia , Polímeros de Fluorcarboneto/metabolismo , Folículo Piloso/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Camundongos Transgênicos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/fisiologia , Nestina/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Células-Tronco Pluripotentes/metabolismo , Polivinil/metabolismo , Medicina Regenerativa/métodos , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/metabolismo
13.
Am J Phys Med Rehabil ; 101(2): 196-200, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35026782

RESUMO

ABSTRACT: Rehabilitation strategies after traumatic spinal cord injury aim to maximize functional recovery by applying principles of neuroplasticity via task-specific, repetitive training. Rehabilitation of patients with traumatic spinal cord injury poses unique challenges, including bilateral limb involvement, autonomic dysfunction, loss of proprioception, and potentially spinal precautions/bracing. The purpose of this retrospective case series was to determine whether use of dynamic body weight support would yield greater improvement in functional recovery compared with standard of care in adults with traumatic spinal cord injury. Data were collected from patients with traumatic spinal cord injury who completed inpatient rehabilitation incorporating dynamic body weight support (n = 5) and who completed inpatient rehabilitation without dynamic body weight support (n = 5). The primary outcome measure was the change in Functional Independence Measures. The dynamic body weight support group had a significantly greater improvement in Total Functional Independence Measures and in Functional Independence Measures motor subscale compared with the standard of care group (P = 0.023 and P = 0.033, respectively). This study presents initial evidence that dynamic body weight support therapy during inpatient rehabilitation has the potential to improve functional independence compared with standard of care in patients with traumatic spinal cord injury. Larger prospective randomized studies need to be conducted to expand on these findings.


Assuntos
Peso Corporal , Aparelhos Ortopédicos , Modalidades de Fisioterapia/instrumentação , Traumatismos da Medula Espinal/reabilitação , Adulto , Idoso , Avaliação da Deficiência , Feminino , Estado Funcional , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Centros de Reabilitação , Estudos Retrospectivos , Traumatismos da Medula Espinal/fisiopatologia , Resultado do Tratamento , Adulto Jovem
14.
PLoS One ; 17(1): e0262864, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35073366

RESUMO

OBJECTIVES: To determine the Effect of Hybrid functional electrically stimulated (FES) Exercise on Body Composition during the Sub-acute Phase of Spinal Cord Injury (SCI). DESIGN: Randomized Clinical Trial. SETTING: Rehabilitation Hospital. PARTICIPANTS: Patients within sub-acute phase (3-24 months) of SCI. INTERVENTIONS: We investigated if high-intensity exercise training via the addition of functional electrically stimulated (FES) leg muscles, provides sufficient stimulus to mitigate against body composition changes in the sub-acute phase after SCI. MAIN OUTCOME MEASURES: We explored potential effects of FES row training (FESRT) on body fat gain, lean mass loss, and cardiometabolic parameters and compared the effects of 6-month of FESRT (n = 18) to standard of care (SOC, n = 13). Those in SOC were crossed over to FESRT. RESULTS: FESRT resulted in greater exercise capacity and a tendency for lesser total body fat accumulation with a significant increase in total and leg lean mass (p<0.05). In addition pelvis and total bone mineral density declines were significantly less (p<0.05). Compared to SOC, FESRT did not lead to any significant difference in insulin sensitivity or serum lipids. However, HbA1C levels were significantly decreased in SOC participants who crossed over to 6-month FESRT. CONCLUSION: FESRT early after SCI provides a sufficient stimulus to mitigate against detrimental body composition changes. This may lead to prevention of losses in lean mass, including bone.


Assuntos
Composição Corporal , Terapia por Estimulação Elétrica , Terapia por Exercício , Músculo Esquelético/fisiopatologia , Traumatismos da Medula Espinal , Adolescente , Adulto , Feminino , Humanos , Masculino , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia
15.
PLoS One ; 17(1): e0262915, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35085340

RESUMO

BACKGROUND: Robotic assisted gait training (RAGT) uses a powered exoskeleton to support an individual's body and move their limbs, with the aim of activating latent, pre-existing movement patterns stored in the lower spinal cord called central pattern generators (CPGs) to facilitate stepping. The parameters that directly stimulate the stepping CPGs (hip extension and ipsilateral foot unloading) should be targeted to maximise the rehabilitation benefits of these devices. AIM: To compare the biomechanical profiles of individuals with a spinal cord injury (SCI) and able-bodied individuals inside the ReWalkTM powered exoskeleton and to contrast the users' profiles with the exoskeleton. METHODS: Eight able-bodied and four SCI individuals donned a ReWalkTM and walked along a 12-meter walkway, using elbow crutches. Whole-body kinematics of the users and the ReWalkTM were captured, along with GRF and temporal-spatial characteristics. Discreet kinematic values were analysed using a Kruskall-Wallis H and Dunn's post-hoc analysis. Upper-body differences, GRF and temporal-spatial characteristics were analysed using a Mann-Whitney U test (P<0.05). RESULTS: Walking speed ranged from 0.32-0.39m/s. Hip abduction, peak knee flexion and ankle dorsiflexion for both the SCI and able-bodied groups presented with significant differences to the ReWalkTM. The able-bodied group presented significant differences to the ReWalkTM for all kinematic variables except frontal plane hip ROM (P = 0.093,δ = -0.56). Sagittal plane pelvic and trunk ROM were significantly greater in the SCI vs. able-bodied (P = 0.004,δ = -1; P = 0.008,δ = -0.94, respectively). Posterior braking force was significantly greater in the SCI group (P = 0.004, δ = -1). DISCUSSION: The different trunk movements used by the SCI group and the capacity for the users' joint angles to exceed those of the device suggest that biomechanical profiles varied according to the user group. However, upright stepping with the ReWalkTM device delivered the appropriate afferent stimulus to activate CPGs as there were no differences in key biomechanical parameters between the two user groups.


Assuntos
Exoesqueleto Energizado , Marcha , Traumatismos da Medula Espinal/fisiopatologia , Caminhada , Adolescente , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
J Chin Med Assoc ; 85(2): 167-174, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34974511

RESUMO

BACKGROUND: Patients with traumatic spinal cord injury (SCI) at C3-C5 have a wide range of tracheostomy rates (27%-75%), and the influencing factors for tracheostomy remain unclear. We conducted a retrospective case-control study to identify the influencing factors for tracheostomy in this subset of patient population. METHODS: A total of 101 acute traumatic C3-C5 SCI patients with acute respiratory failure requiring translaryngeal intubation and invasive mechanical ventilation (IMV) for more than 48 hours were identified and divided into the no tracheostomy (No-TCO, n = 59) and tracheostomy group (TCO, n = 42) groups. Clinical data were retrospectively reviewed and analyzed. RESULTS: Compared with the No-TCO patients, the TCO patients had a higher proportion of C3 level injury, lower Glasgow Coma Scale (GCS), and lower blood hemoglobin levels at admission. During the first weaning attempt, the TCO patients had lower levels of maximal inspiratory pressure, maximal expiratory pressure, and minute ventilation but had a higher level of rapid shallow breathing index (RSBI). The TCO patients had longer durations of IMV, ICU stay, and hospitalization compared with the No-TCO patients. Moreover, due to prolonged IMV, the TCO patients had a higher incidence of complications, including ventilator-associated pneumonia, bacteremia, urinary tract infection, and acute kidney injury compared with the No-TCO patients. Multivariate logistic regression analysis revealed that low GCS at admission and high initial RSBI were independent risk factors for tracheostomy. Importantly, a combination of these two influencing factors synergistically increased the odds ratio for tracheostomy. CONCLUSION: Low GCS at admission and high initial RSBI are two independent influencing factors that synergistically impact tracheostomy in our patients. These findings are helpful for making the decision of performing tracheostomy in this subset of patient population.


Assuntos
Síndrome do Desconforto Respiratório , Traumatismos da Medula Espinal/fisiopatologia , Traqueostomia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Taiwan
17.
Int J Mol Sci ; 23(2)2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-35054791

RESUMO

Spinal cord injury (SCI) produces paralysis and a unique form of neurogenic disuse osteoporosis that dramatically increases fracture risk at the distal femur and proximal tibia. This bone loss is driven by heightened bone resorption and near-absent bone formation during the acute post-SCI recovery phase and by a more traditional high-turnover osteopenia that emerges more chronically, which is likely influenced by the continual neural impairment and musculoskeletal unloading. These observations have stimulated interest in specialized exercise or activity-based physical therapy (ABPT) modalities (e.g., neuromuscular or functional electrical stimulation cycling, rowing, or resistance training, as well as other standing, walking, or partial weight-bearing interventions) that reload the paralyzed limbs and promote muscle recovery and use-dependent neuroplasticity. However, only sparse and relatively inconsistent evidence supports the ability of these physical rehabilitation regimens to influence bone metabolism or to increase bone mineral density (BMD) at the most fracture-prone sites in persons with severe SCI. This review discusses the pathophysiology and cellular/molecular mechanisms that influence bone loss after SCI, describes studies evaluating bone turnover and BMD responses to ABPTs during acute versus chronic SCI, identifies factors that may impact the bone responses to ABPT, and provides recommendations to optimize ABPTs for bone recovery.


Assuntos
Osso e Ossos/patologia , Exercício Físico/fisiologia , Modalidades de Fisioterapia , Traumatismos da Medula Espinal/terapia , Animais , Densidade Óssea , Remodelação Óssea/fisiologia , Osso e Ossos/fisiopatologia , Humanos , Traumatismos da Medula Espinal/fisiopatologia
18.
Dis Markers ; 2022: 5389162, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35082930

RESUMO

OBJECTIVE: Spinal cord injury (SCI) has become popular in recent years, and cognitive decline is a common complication. Adiponectin is a common protein hormone involved in the course of many diseases, but its relationship with SCI has not yet been elucidated. The purpose of our prospective study is to explore whether adiponectin can be used as a biomarker of cognitive decline in SCI. METHODS: A total of 64 healthy volunteers and 92 patients with acute SCI were recruited by us. Serum adiponectin levels, demographic data (age and gender), lifestyle (smoking and drinking), medical history (diabetes and hypertension), and clinical baseline data (low-density lipoprotein, high-density lipoprotein, and fasting blood glucose) were recorded. Three months after enrollment, we used the Montreal Cognitive Assessment (MoCA) to evaluate cognitive function. Based on a quarter of the serum adiponectin levels, SCI patients were divided into 4 groups, and the differences in their MoCA scores were compared. In addition, we used multivariate linear regression to predict the risk factors of the MoCA score. RESULTS: The serum adiponectin level (6.1 ± 1.1 µg/ml) of SCI patients was significantly lower than that of the healthy control group (6.7 ± 0.9 µg/ml), and there was a significant difference between the two (p < 0.001). The group with higher serum adiponectin levels after 3 months of spinal cord injury had higher MoCA scores. Multivariate regression analysis showed that serum adiponectin level is a protective factor for cognitive function after SCI (ß = 0.210, p = 0.043). CONCLUSIONS: Serum adiponectin levels can be used as an independent predictor of cognitive function in patients with acute SCI.


Assuntos
Adiponectina/sangue , Disfunção Cognitiva/sangue , Índice de Gravidade de Doença , Traumatismos da Medula Espinal/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Disfunção Cognitiva/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Traumatismos da Medula Espinal/fisiopatologia
19.
Brain Res Bull ; 180: 59-72, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34995751

RESUMO

After spinal cord injury (SCI), endogenous angiogenesis occurs in the injury core, unexpectedly accompanied by continuous leakage of the blood-spinal cord barrier (BSCB), which may be caused by destruction of the tight junctions (TJs) between vascular endothelial cells-an important structure of the BSCB. Blood-derived macrophages infiltrate into the spinal cord, aggregate to the injury core and then polarize toward M1/M2 phenotypes after SCI. However, the effect of macrophages with different polarizations on the TJs between vascular endothelial cells remains unclear. Here, we demonstrated that from 7 days postinjury (dpi) to 28 dpi, accompanied by the aggregation of macrophages, the expression of claudin-5 (CLN-5) and zonula occludens-1 (ZO-1) in vascular endothelial cells in the injury core was significantly decreased in comparison to that in normal spinal cord tissue and in the penumbra. Moreover, the leakage of the BSCB was severe in the injury core, as demonstrated by FITC-dextran perfusion. Notably, our study demonstrated that depletion of macrophages facilitated the restoration of TJs between vascular endothelial cells and decreased the leakage of BSCB in the injury core after SCI. Furthermore, we confirmed that the endothelial TJs could be impaired by M1 macrophages through secreting IL-6 in vitro, leading to an increased permeability of endothelial cells, but it was not significantly affected by M0 and M2 macrophages. These results indicated that the TJs between vascular endothelial cells were impaired by M1 macrophages in the injury core, potentially resulting in continuous leakage of the BSCB after SCI. Preventing M1 polarization of macrophages or blocking IL-6 in the injury core may promote restoration of the BSCB, thus accelerating functional recovery after SCI.


Assuntos
Células Endoteliais/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Traumatismos da Medula Espinal , Junções Íntimas/fisiologia , Animais , Modelos Animais de Doenças , Ratos , Traumatismos da Medula Espinal/imunologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia
20.
Exp Neurol ; 348: 113937, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34826427

RESUMO

Neurogenic lower urinary tract dysfunction typically develops after spinal cord injury. We investigated the time course and the anatomical changes in the spinal cord that may be causing lower urinary tract symptoms following injury. Rats were implanted with a bladder catheter and external urethral sphincter electromyography electrodes. Animals underwent a large, incomplete spinal transection at the T8/9 spinal level. At 1, 2-3, and 4 weeks after injury, the animals underwent urodynamic investigations. Urodynamic investigations showed detrusor overactivity and detrusor-sphincter-dyssynergia appearing over time at 3-4 weeks after injury. Lower urinary tract dysfunction was accompanied by an increase in density of C-fiber afferents in the lumbosacral dorsal horn. CRF-positive Barrington's and 5-HT-positive bulbospinal projections drastically decreased after injury, with partial compensation for the CRF fibers at 3-4 weeks. Interestingly, a decrease over time was observed in the number of GABAergic neurons in the lumbosacral dorsal horn and lamina X, and a decrease of glutamatergic cells in the dorsal horn. Detrusor overactivity and detrusor-sphincter-dyssynergia might therefore arise from a discrepancy in inhibitory/excitatory interneuron activity in the lumbosacral cord as well as input changes which develop over time after injury. The processes point to spinal plastic changes leading to malfunction of the important physiological pathway of lower urinary tract control.


Assuntos
Interneurônios/fisiologia , Fibras Nervosas Amielínicas/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Bexiga Urinaria Neurogênica/fisiopatologia , Bexiga Urinária/inervação , Bexiga Urinária/fisiopatologia , Animais , Neurônios Colinérgicos/fisiologia , Eletromiografia/métodos , Feminino , Neurônios GABAérgicos/fisiologia , Vértebras Lombares/lesões , Ratos , Ratos Endogâmicos Lew , Sacro/lesões , Traumatismos da Medula Espinal/complicações , Bexiga Urinaria Neurogênica/etiologia
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