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1.
Am J Phys Med Rehabil ; 100(11): 1034-1041, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34673705

RESUMO

OBJECTIVE: The first objective was to identify a method for early prediction of independent outdoor functional walking 1 yr after a traumatic spinal cord injury using the motor and sensory function derived from the International Standards for Neurological Classification of Spinal Cord Injury assessment during acute care. Then, the second objective was to develop a clinically relevant prediction rule that would be accurate, easy to use, and quickly calculated in clinical setting. DESIGN: A prospective cohort of 159 traumatic spinal cord injury patients was analyzed. Bivariate correlations were used to determine the assessment method of motor strength and sensory function as well as the specific dermatomes and myotomes best associated with independent outdoor functional walking 1 yr after injury. An easy-to-use clinical prediction rule was produced using a multivariable linear regression model. RESULTS: The highest motor strength for a given myotome (L3 and L5) and preserved light touch sensation (dermatome S1) were the best predictors of the outcome. The proposed prediction rule displayed a sensitivity of 84.21%, a specificity of 85.54%, and a global accuracy of 84.91% for classification. CONCLUSIONS: After an acute traumatic spinal cord injury, accurately predicting the ability to walk is challenging. The proposed clinical prediction rule aims to enhance previous work by identifying traumatic spinal cord injury patients who will reach a mobility level that fosters social participation and quality of life in the chronic period after the injury. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Revise the different motor and sensory function assessment methods used for prognostication of walking after an acute traumatic spinal cord injury; (2) Identify clinical factors that are significantly associated with functional walking 1 yr after a traumatic spinal cord injury; and (3) Accurately estimate the likelihood of reaching independent outdoor functional walking in the chronic phase after an acute traumatic spinal cord injury. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.


Assuntos
Regras de Decisão Clínica , Avaliação da Deficiência , Estado Funcional , Traumatismos da Medula Espinal/diagnóstico , Adulto , Idoso , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Traumatismos da Medula Espinal/fisiopatologia , Caminhada
2.
Cells ; 10(10)2021 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-34685763

RESUMO

Aldynoglia are growth-promoting cells with a morphology similar to radial glia and share properties and markers with astrocytes and Schwann cells. They are distributed in several locations throughout the adult central nervous system, where the cells of the aldynoglia interact and respond to the signals of the immune cells. After spinal cord injury (SCI), the functions of resident aldynoglia, identified as ependymocytes, tanycytes, and ependymal stem cells (EpSCs) of the spinal cord are crucial for the regeneration of spinal neural tissue. These glial cells facilitate axonal regrowth and remyelination of injured axons. Here, we review the influence of M1 or M2 macrophage/microglia subpopulations on the fate of EpSCs during neuroinflammation and immune responses in the acute, subacute, and chronic phases after SCI.


Assuntos
Inflamação/imunologia , Inflamação/patologia , Neuroglia/patologia , Neurônios/imunologia , Neurônios/patologia , Traumatismos da Medula Espinal/imunologia , Traumatismos da Medula Espinal/patologia , Animais , Humanos , Imunidade , Regeneração Nervosa , Traumatismos da Medula Espinal/fisiopatologia
3.
Molecules ; 26(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34641529

RESUMO

Neurodegenerative diseases (NDDs) are one of the leading causes of death and disability in humans. From a mechanistic perspective, the complexity of pathophysiological mechanisms contributes to NDDs. Therefore, there is an urgency to provide novel multi-target agents towards the simultaneous modulation of dysregulated pathways against NDDs. Besides, their lack of effectiveness and associated side effects have contributed to the lack of conventional therapies as suitable therapeutic agents. Prevailing reports have introduced plant secondary metabolites as promising multi-target agents in combating NDDs. Polydatin is a natural phenolic compound, employing potential mechanisms in fighting NDDs. It is considered an auspicious phytochemical in modulating neuroinflammatory/apoptotic/autophagy/oxidative stress signaling mediators such as nuclear factor-κB (NF-κB), NF-E2-related factor 2 (Nrf2)/antioxidant response elements (ARE), matrix metalloproteinase (MMPs), interleukins (ILs), phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt), and the extracellular regulated kinase (ERK)/mitogen-activated protein kinase (MAPK). Accordingly, polydatin potentially counteracts Alzheimer's disease, cognition/memory dysfunction, Parkinson's disease, brain/spinal cord injuries, ischemic stroke, and miscellaneous neuronal dysfunctionalities. The present study provides all of the neuroprotective mechanisms of polydatin in various NDDs. Additionally, the novel delivery systems of polydatin are provided regarding increasing its safety, solubility, bioavailability, and efficacy, as well as developing a long-lasting therapeutic concentration of polydatin in the central nervous system, possessing fewer side effects.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Glucosídeos/farmacologia , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Estilbenos/farmacologia , Animais , Transtornos Cognitivos/tratamento farmacológico , Glucosídeos/administração & dosagem , Glucosídeos/química , Glucosídeos/uso terapêutico , Humanos , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/fisiopatologia , Estilbenos/administração & dosagem , Estilbenos/química , Estilbenos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico
4.
Int J Mol Sci ; 22(18)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34575871

RESUMO

The pathobiology of traumatic and nontraumatic spinal cord injury (SCI), including degenerative myelopathy, is influenced by neuroinflammation. The neuroinflammatory response is initiated by a multitude of injury signals emanating from necrotic and apoptotic cells at the lesion site, recruiting local and infiltrating immune cells that modulate inflammatory cascades to aid in the protection of the lesion site and encourage regenerative processes. While peripheral immune cells are involved, microglia, the resident immune cells of the central nervous system (CNS), are known to play a central role in modulating this response. Microglia are armed with numerous cell surface receptors that interact with neurons, astrocytes, infiltrating monocytes, and endothelial cells to facilitate a dynamic, multi-faceted injury response. While their origin and essential nature are understood, their mechanisms of action and spatial and temporal profiles warrant extensive additional research. In this review, we describe the role of microglia and the cellular network in SCI, discuss tools for their investigation, outline their spatiotemporal profile, and propose translationally-relevant therapeutic targets to modulate neuroinflammation in the setting of SCI.


Assuntos
Inflamação/metabolismo , Microglia/metabolismo , Neurônios/metabolismo , Traumatismos da Medula Espinal/metabolismo , Animais , Astrócitos/metabolismo , Membrana Celular/metabolismo , Células Endoteliais/metabolismo , Humanos , Imunidade Inata , Inflamação/fisiopatologia , Macrófagos/metabolismo , Monócitos/metabolismo , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia
5.
Elife ; 102021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34586065

RESUMO

Sensory neurons with cell bodies in dorsal root ganglia (DRG) represent a useful model to study axon regeneration. Whereas regeneration and functional recovery occurs after peripheral nerve injury, spinal cord injury or dorsal root injury is not followed by regenerative outcomes. Regeneration of sensory axons in peripheral nerves is not entirely cell autonomous. Whether the DRG microenvironment influences the different regenerative capacities after injury to peripheral or central axons remains largely unknown. To answer this question, we performed a single-cell transcriptional profiling of mouse DRG in response to peripheral (sciatic nerve crush) and central axon injuries (dorsal root crush and spinal cord injury). Each cell type responded differently to the three types of injuries. All injuries increased the proportion of a cell type that shares features of both immune cells and glial cells. A distinct subset of satellite glial cells (SGC) appeared specifically in response to peripheral nerve injury. Activation of the PPARα signaling pathway in SGC, which promotes axon regeneration after peripheral nerve injury, failed to occur after central axon injuries. Treatment with the FDA-approved PPARα agonist fenofibrate increased axon regeneration after dorsal root injury. This study provides a map of the distinct DRG microenvironment responses to peripheral and central injuries at the single-cell level and highlights that manipulating non-neuronal cells could lead to avenues to promote functional recovery after CNS injuries or disease.


Assuntos
Gânglios Espinais/citologia , Células Receptoras Sensoriais/fisiologia , Animais , Axônios , Biomarcadores/metabolismo , Proliferação de Células , Microambiente Celular , Fenofibrato/administração & dosagem , Gânglios Espinais/metabolismo , Macrófagos/citologia , Camundongos , PPAR alfa/metabolismo , Células Receptoras Sensoriais/citologia , Células Receptoras Sensoriais/metabolismo , Análise de Célula Única , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia
6.
Int J Mol Sci ; 22(15)2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34360697

RESUMO

BACKGROUND: Spinal cord injury (SCI) causes a primary injury at the lesion site and triggers a secondary injury and prolonged inflammation. There has been no definitive treatment till now. Promoting angiogenesis is one of the most important strategies for functional recovery after SCI. The omentum, abundant in blood and lymph vessels, possesses the potent ability of tissue regeneration. METHODS: The present work examines the efficacy of autologous omentum, either as a flap (with vascular connection intact) or graft (severed vascular connection), on spinal nerve regeneration. After contusive SCI in rats, a thin sheath of omentum was grafted to the injured spinal cord. RESULTS: Omental graft improved behavior scores significantly from the 3rd to 6th week after injury (6th week, 5.5 ± 0.5 vs. 8.6 ± 1.3, p < 0.05). Furthermore, the reduction in cavity and the preservation of class III ß-tubulin-positive nerve fibers in the injury area was noted. Next, the free omental flap was transposed to a completely transected SCI in rats through a pre-implanted tunnel. The flap remained vascularized and survived well several weeks after the operation. At 16 weeks post-treatment, SCI rats with omentum flap treatment displayed the preservation of significantly more nerve fibers (p < 0.05) and a reduced injured cavity, though locomotor scores were similar. CONCLUSIONS: Taken together, the findings of this study indicate that treatment with an omental graft or transposition of an omental flap on an injured spinal cord has a positive effect on nerve protection and tissue preservation in SCI rats. The current data highlight the importance of omentum in clinical applications.


Assuntos
Omento/transplante , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/cirurgia , Regeneração da Medula Espinal , Medula Espinal/cirurgia , Retalhos Cirúrgicos/transplante , Animais , Neuroproteção , Ratos , Medula Espinal/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Retalhos Cirúrgicos/irrigação sanguínea , Transplante Autólogo , Resultado do Tratamento
7.
Biomed Res Int ; 2021: 3376496, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337004

RESUMO

Lactobacillus rhamnoides, a human intestinal colonizer, can act through various pathways to induce microglia/macrophages to produce cytokines and to polarize microglia/macrophages to different phenotypes to reduce the inflammatory response. In this article, we evaluated the treatment potential of the Lactobacillus rhamnoides GG conditioned medium (LGG-CM) in rat model with SCI (acute spinal cord injury), including functional, neurophysiological, and histological outcomes and the underlying neuroprotective mechanisms. In our experiment, LGG-CM (30 mg/kg) was injected directly into the injury site in rats immediately after SCI. Measured by the BBB scale (Basso, Beattie, and Bresnahan locomotor rating scale) and inclined plane test, rats in the LGG-CM-treated group showed better locomotor scores. Moreover, compared to the vehicle treatment group, LGG-CM increased the mRNA level of the M2 marker (CD206), and decreased that of the M1 marker (iNOS). Western blot assays showed that LGG-CM-treated SCI rats had a higher grayscale ratio of p65 and a lower ratio of p-IκBα/IκBα. Our study shows that local injection of LGG-CM after acute SCI can inhibit inflammatory responses and improve motor function recovery. These effects may be related with the inhibition to the NF-κB (The nuclear factor-kappa B) signal pathway which leads to M2 microglia/macrophage polarization.


Assuntos
Polaridade Celular , Meios de Cultivo Condicionados/farmacologia , Lactobacillus rhamnosus/química , Macrófagos/patologia , Microglia/patologia , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/fisiopatologia , Animais , Polaridade Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Inflamação/patologia , Macrófagos/efeitos dos fármacos , Microglia/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Recuperação de Função Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
8.
Biomolecules ; 11(7)2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34356596

RESUMO

Traumatic spinal cord injury (SCI) impairs neuronal function and introduces a complex cascade of secondary pathologies that limit recovery. Despite decades of preclinical and clinical research, there is a shortage of efficacious treatment options to modulate the secondary response to injury. Protein kinases are crucial signaling molecules that mediate the secondary SCI-induced cellular response and present promising therapeutic targets. The objective of this study was to examine the safety and efficacy of midostaurin-a clinically-approved multi-target protein kinase inhibitor-on cervical SCI pathogenesis. High-throughput analyses demonstrated that intraperitoneal midostaurin injection (25 mg/kg) in C6/7 injured Wistar rats altered the local inflammasome and downregulated adhesive and migratory genes at 24 h post-injury. Treated animals also exhibited enhanced recovery and restored coordination between forelimbs and hindlimbs after injury, indicating the synergistic impact of midostaurin and its dimethyl sulfoxide vehicle to improve functional recovery. Furthermore, histological analyses suggested improved tissue preservation and functionality in the treated animals during the chronic phase of injury. This study serves as a proof-of-concept experiment and demonstrates that systemic midostaurin administration is an effective strategy for mitigating cervical secondary SCI damage.


Assuntos
Medula Cervical , Fármacos Neuroprotetores/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Traumatismos da Medula Espinal , Estaurosporina/análogos & derivados , Animais , Medula Cervical/lesões , Medula Cervical/metabolismo , Medula Cervical/fisiopatologia , Feminino , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/fisiopatologia , Ratos , Ratos Wistar , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Estaurosporina/farmacologia
9.
Top Spinal Cord Inj Rehabil ; 27(3): 49-59, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456546

RESUMO

Objectives: To establish predictive equations for peak torque of muscle groups with totally and partially preserved innervation in individuals with motor complete spinal cord injury (SCI), based on hand dynamometry and strength predictor variables. Methods: The cross-sectional study conducted at a rehabilitation hospital consecutively recruited 108 men and women with SCI. All participants performed maximum peak torque tests for shoulder abduction/adduction (isokinetic), trunk flexion/extension (isometric), and handgrip strength testing (hand dynamometer) to establish predictive peak torque equations. The primary outcomes were peak torque variables. Handgrip strength, age, injury level, time since injury, age at injury, body mass, height, body mass index, and physical activity level were the secondary outcomes used as strength predictor variables. Results: Handgrip strength was a predictor variable for shoulder abduction/adduction peak torque. The best predictive models for shoulder abduction/adduction peak torque exhibited R 2 = 0.57 and R 2 = 0.60, respectively (p ≤ .05). Injury level showed the highest significant predictive capacity for trunk flexion/extension peak torque models (R 2 = 0.38 and R 2 = 0.29; p ≤ .05). Conclusion: Shoulder abduction/adduction peak torque predictive equations may be an alternative for use in an accessible strength tool (hand dynamometry) to evaluate training and rehabilitation programs. Trunk flexion/extension peak torque equations exhibited moderate correlations and high standard error of the estimates and should be used with caution.


Assuntos
Força da Mão/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Força Muscular/fisiologia , Dinamômetro de Força Muscular , Valor Preditivo dos Testes , Torque , Adulto Jovem
10.
Top Spinal Cord Inj Rehabil ; 27(3): 60-69, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456547

RESUMO

Objectives: To determine optimal handgrip strength (HGS) cutoff points for greater functional independence and wheelchair skills in men with spinal cord injury (SCI), and to establish predictive equations for functional independence and wheelchair ability in men with SCI, based on demographic characteristics, HGS, and functionality. Methods: In this cross-sectional study conducted at a rehabilitation hospital, 54 men with SCI were recruited and stratified into high and low paraplegia groups. All participants performed a maximum HGS test to determine cutoff points for the Spinal Cord Independence Measure (SCIM-III) and Adapted Manual Wheelchair Circuit (AMWC). The primary outcomes were the SCIM-III, AMWC, and HGS. Demographic characteristics obtained from participants' electronic medical records were the secondary outcomes, used as predictor variables of functional independence. Results: The SCIM-III scale, performance score, and 3-minute overground wheeling test presented significant regression equations (R = 0.45, R = 0.69, and R = 0.72). The HGS showed a cutoff point of 102.5 kilogram force (kgf) to achieve a score of 70 on the SCIM-III and a 3-minute overground wheeling distance of 270 m. The HGS cutoff point to obtain a performance score of 23.7 seconds was 93.0 kgf. Conclusion: The HGS was a significant predictor for the SCIM-III score, AMWC performance score, and 3-minute overground wheeling test. Three significant predictive equations were established based on HGS. The cutoff points could be adopted as parameters for optimal functional independence and wheelchair skills.


Assuntos
Estado Funcional , Força da Mão/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/reabilitação , Cadeiras de Rodas , Adulto , Estudos Transversais , Humanos , Masculino , Valor Preditivo dos Testes , Adulto Jovem
11.
Top Spinal Cord Inj Rehabil ; 27(3): 70-82, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456548

RESUMO

Objectives: To reach agreement on standardized protocols for assessing upper limb strength and grip and pinch force for upper limb reconstructive surgery for tetraplegia. Methods: Selected members of an expert panel composed of international therapists formed at the 2018 International Congress for Upper Limb Surgery for Tetraplegia conducted a literature review of current practice that identified gaps and inconsistencies in measurement protocols and presented to workshop attendees. To resolve discrepancies, a set of questions was presented to workshop attendees who voted electronically. Consensus was set at 75% agreement. Results: For manual muscle testing, consensus was reached for using the Medical Research Council scale, without plus or minus, and the use of resistance through range when testing grade 4 and grade 5 strength. Pectoralis major and serratus anterior should be routinely tested, however there was no consensus on other shoulder muscles. Grip and pinch strength should be tested according to the American Society of Hand Therapists positioning. For grip strength, either the Jamar or Biometrics dynamometer expressed in kilograms should be used. For grip and pinch strength, three measurements should be performed at each testing. No consensus was reached on a device for pinch strength. Conclusion: This work is an important step to enable comparable data in the future. Further consensus methods will work toward developing more comprehensive guidelines in this population. Building international consensus for pre- and postoperative measures of function supports objective evaluation of novel therapies and interpretation of multicenter studies.


Assuntos
Força Muscular/fisiologia , Exame Físico/normas , Quadriplegia/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Extremidade Superior/fisiopatologia , Extremidade Superior/cirurgia , Humanos , Quadriplegia/cirurgia , Procedimentos Cirúrgicos Reconstrutivos , Traumatismos da Medula Espinal/cirurgia
12.
Am J Physiol Heart Circ Physiol ; 321(4): H716-H727, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34448635

RESUMO

Spinal cord injury (SCI) impairs the cardiovascular responses to postural challenge, leading to the development of orthostatic hypotension (OH). Here, we apply lower body negative pressure (LBNP) to rodents with high-level SCI to demonstrate the usefulness of LBNP as a model for experimental OH studies, and to explore the effect of simulated OH on cardiovascular and cerebrovascular function following SCI. Male Wistar rats (n = 34) were subjected to a sham or T3-SCI surgery and survived into the chronic period postinjury (i.e., 8 wk). Cardiac function was tracked via ultrasound pre- to post-SCI to demonstrate the clinical utility of our model. At study termination, we conducted left-ventricular (LV) catheterization and insonated the middle cerebral artery to investigate the hemodynamic, cardiac, and cerebrovascular response to a mild dose of LBNP that is sufficient to mimic clinically defined OH in rats with T3-SCI but not sham animals. In response to mimicked OH, there was a greater decline in stroke volume, cardiac output, maximal LV pressure, and blood pressure in SCI compared with sham (P < 0.034), whereas heart rate was increased in sham but decreased in SCI (P < 0.029). SCI animals also had an exaggerated reduction in peak, minimum and mean middle cerebral artery flow, for a given change in blood pressure, in response to LBNP (P < 0.033), implying impaired dynamic cerebral autoregulation. Using a preclinical SCI model of OH, we demonstrate that complete high thoracic SCI impairs the cardiac response to OH and disrupts dynamic cerebral autoregulation.NEW & NOTEWORTHY This is the first use of LBNP to interrogate the cardiac and cerebrovascular responses to simulated OH in a preclinical study of SCI. Here, we demonstrate the utility of our simulated OH model and use it to demonstrate that SCI impairs the cardiac response to simulated OH and disrupts dynamic cerebrovascular autoregulation.


Assuntos
Circulação Cerebrovascular , Hemodinâmica , Hipotensão Ortostática/fisiopatologia , Artéria Cerebral Média/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/fisiopatologia , Função Ventricular Esquerda , Adaptação Fisiológica , Animais , Modelos Animais de Doenças , Hipotensão Ortostática/etiologia , Pressão Negativa da Região Corporal Inferior , Masculino , Ratos Wistar , Traumatismos da Medula Espinal/complicações , Vértebras Torácicas , Fatores de Tempo
13.
Sci Rep ; 11(1): 15892, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354119

RESUMO

Neurogenic bowel dysfunction, including hyperreflexic and areflexic bowel, is a common complication in patients with spinal cord injury (SCI). We hypothesized that removing part of the colonic sympathetic innervation can alleviate the hyperreflexic bowel, and investigated the effect of sympathectomy on the hyperreflexic bowel of SCI rats. The peri-arterial sympathectomy of the inferior mesenteric artery (PSIMA) was performed in T8 SCI rats. The defecation habits of rats, the water content of fresh faeces, the intestinal transmission function, the defecation pressure of the distal colon, and the down-regulation of Alpha-2 adrenergic receptors in colon secondary to PSIMA were evaluated. The incidence of typical hyperreflexic bowel was 95% in SCI rats. Compared to SCI control rats, PSIMA increased the faecal water content of SCI rats by 5-13% (P < 0.05), the emptying rate of the faeces in colon within 24 h by 14-40% (P < 0.05), and the defecation pressure of colon by 10-11 mmHg (P < 0.05). These effects lasted for at least 12 weeks after PSIMA. Immunofluorescence label showed the secondary down-regulation of Alpha-2 adrenergic receptors after PSIMA occurred mainly in rats' distal colon. PSIMA mainly removes the sympathetic innervation of the distal colon, and can relieve the hyperreflexic bowel in rats with SCI. The possible mechanism is to reduce the inhibitory effect of sympathetic activity, and enhance the regulatory effect of parasympathetic activity on the colon. This procedure could potentially be used for hyperreflexic bowel in patients with SCI.


Assuntos
Intestino Neurogênico/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Simpatectomia/métodos , Animais , Colo/fisiopatologia , Defecação/fisiologia , Fezes , Feminino , Motilidade Gastrointestinal/fisiologia , Masculino , Modelos Animais , Intestino Neurogênico/complicações , Intestino Neurogênico/cirurgia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/complicações
14.
Top Spinal Cord Inj Rehabil ; 27(3): 12-25, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456543

RESUMO

Background: Individuals with spinal cord injury (SCI) who use manual wheelchairs (MWCs) have a higher rate of rotator cuff pathology progression than able-bodied individuals. Objectives: This study aimed to test the ability of risk and recovery metrics of arm use to differentiate between (1) MWC users with SCI and matched able-bodied participants (cross-sectional matched-sample study) and (2) MWC users with rotator cuff pathology progression over 1 year from those without pathology progression (longitudinal study). Methods: Thirty-four MWC users and 34 age- and sex-matched able-bodied individuals were recruited. Upper arm risk (humeral elevation >60°) and recovery (static ≥5 seconds and humeral elevation <40°) metrics were calculated from wireless inertial measurement units (IMUs) worn on the upper arms and torso in the free-living environment. Two separate magnetic resonance imaging studies were completed and assessed for a subset of 16 MWC users approximately 1 year apart. Results: The frequency of risk events (p = .019), summated duration of recovery events (p = .025), and duration of each recovery event (p = .003) were higher for MWC users than able-bodied participants. The summated duration of risk events (p = .047), frequency of risk events (p = .027), and risk to recovery ratio (p = .02) were higher and the summated duration of recovery events (p = .036) and frequency of recovery events (p = .047) were lower for MWC users with rotator cuff pathology progression (n = 5) compared to those without progression (n = 11). Conclusion: IMU-derived metrics quantifying arm use at postures >60° and risk to recovery ratios may provide insights of potential risk factors for rotator cuff pathology progression.


Assuntos
Transtornos Traumáticos Cumulativos/fisiopatologia , Ergonomia/métodos , Lesões do Ombro/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/reabilitação , Cadeiras de Rodas/efeitos adversos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
15.
Cells ; 10(8)2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34440641

RESUMO

Spinal cord injury (SCI) is a debilitating condition, often leading to severe motor, sensory, or autonomic nervous dysfunction. As the holy grail of regenerative medicine, promoting spinal cord tissue regeneration and functional recovery are the fundamental goals. Yet, effective regeneration of injured spinal cord tissues and promotion of functional recovery remain unmet clinical challenges, largely due to the complex pathophysiology of the condition. The transplantation of various cells, either alone or in combination with three-dimensional matrices, has been intensively investigated in preclinical SCI models and clinical trials, holding translational promise. More recently, a new paradigm shift has emerged from cell therapy towards extracellular vesicles as an exciting "cell-free" therapeutic modality. The current review recapitulates recent advances, challenges, and future perspectives of cell-based spinal cord tissue engineering and regeneration strategies.


Assuntos
Vesículas Extracelulares/transplante , Regeneração Nervosa , Células-Tronco Neurais/transplante , Traumatismos da Medula Espinal/cirurgia , Medula Espinal/fisiopatologia , Transplante de Células-Tronco , Engenharia Tecidual , Animais , Vesículas Extracelulares/metabolismo , Humanos , Células-Tronco Neurais/metabolismo , Neurogênese , Fenótipo , Recuperação de Função Fisiológica , Medula Espinal/metabolismo , Medula Espinal/patologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/instrumentação , Tecidos Suporte
16.
Cells ; 10(8)2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34440655

RESUMO

Complete spinal cord injury (SCI) leads to permanent motor, sensitive and sensory deficits. In humans, there is currently no therapy to promote recovery and the only available treatments include surgical intervention to prevent further damage and symptomatic relief of pain and infections in the acute and chronic phases, respectively. Basically, the spinal cord is classically viewed as a nonregenerative tissue with limited plasticity. Thereby the establishment of the "glial" scar which appears within the SCI is mainly described as a hermetic barrier for axon regeneration. However, recent discoveries have shed new light on the intrinsic functional plasticity and endogenous recovery potential of the spinal cord. In this review, we will address the different aspects that the spinal cord plasticity can take on. Indeed, different experimental paradigms have demonstrated that axonal regrowth can occur even after complete SCI. Moreover, recent articles have demonstrated too that the "glial" scar is in fact composed of several cellular populations and that each of them exerts specific roles after SCI. These recent discoveries underline the underestimation of the plasticity of the spinal cord at cellular and molecular levels. Finally, we will address the modulation of this endogenous spinal cord plasticity and the perspectives of future therapeutic opportunities which can be offered by modulating the injured spinal cord microenvironment.


Assuntos
Regeneração Nervosa , Células-Tronco Neurais/patologia , Plasticidade Neuronal , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/fisiopatologia , Nervos Espinhais/fisiopatologia , Animais , Humanos , Células-Tronco Neurais/metabolismo , Neuroglia/metabolismo , Neuroglia/patologia , Fenótipo , Recuperação de Função Fisiológica , Medula Espinal/metabolismo , Medula Espinal/patologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/reabilitação , Nervos Espinhais/lesões , Nervos Espinhais/metabolismo , Nervos Espinhais/patologia
17.
Cells ; 10(8)2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34440711

RESUMO

Microglia and astrocytes play an important role in the regulation of immune responses under various pathological conditions. To detect environmental cues associated with the transformation of reactive microglia (M1) and astrocytes (A1) into their polarization states (anti-inflammatory M2 and A2 phenotypes), we studied time-dependent gene expression in naive and injured spinal cord. The relationship between astrocytes and microglia and their polarization states were studied in a rat model after Th9 compression (40 g/15 min) in acute and subacute stages at the lesion site, and both cranially and caudally. The gene expression of microglia/macrophages and M1 microglia was strongly up-regulated at the lesion site and caudally one week after SCI, and attenuated after two weeks post-SCI. GFAP and S100B, and A1 astrocytes were profoundly expressed predominantly two weeks post-SCI at lesion site and cranially. Gene expression of anti-inflammatory M2a microglia (CD206, CHICHI, IL1rn, Arg-1), M2c microglia (TGF-ß, SOCS3, IL4R α) and A2 astrocytes (Tgm1, Ptx3, CD109) was greatly activated at the lesion site one week post-SCI. In addition, we observed positive correlation between neurological outcome and expression of M2a, M2c, and A2 markers. Our findings indicate that the first week post-injury is critical for modulation of reactive microglia/astrocytes into their neuroprotective phenotypes.


Assuntos
Astrócitos/metabolismo , Comportamento Animal , Mediadores da Inflamação/metabolismo , Locomoção , Microglia/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Traumatismos da Medula Espinal/metabolismo , Medula Espinal/metabolismo , Animais , Astrócitos/imunologia , Astrócitos/patologia , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Macrófagos/imunologia , Macrófagos/metabolismo , Microglia/imunologia , Microglia/patologia , Proteínas do Tecido Nervoso/genética , Fenótipo , Ratos Wistar , Recuperação de Função Fisiológica , Transdução de Sinais , Medula Espinal/imunologia , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/imunologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Fatores de Tempo
18.
Cells ; 10(8)2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34440784

RESUMO

CNS neurons are generally incapable of regenerating their axons after injury due to several intrinsic and extrinsic factors, including the presence of axon growth inhibitory molecules. One such potent inhibitor of CNS axon regeneration is Reticulon (RTN) 4 or Nogo-A. Here, we focused on RTN3 as its contribution to CNS axon regeneration is currently unknown. We found that RTN3 expression correlated with an axon regenerative phenotype in dorsal root ganglion neurons (DRGN) after injury to the dorsal columns, a well-characterised model of spinal cord injury. Overexpression of RTN3 promoted disinhibited DRGN neurite outgrowth in vitro and dorsal column axon regeneration/sprouting and electrophysiological, sensory and locomotor functional recovery after injury in vivo. Knockdown of protrudin, however, ablated RTN3-enhanced neurite outgrowth/axon regeneration in vitro and in vivo. Moreover, overexpression of RTN3 in a second model of CNS injury, the optic nerve crush injury model, enhanced retinal ganglion cell (RGC) survival, disinhibited neurite outgrowth in vitro and survival and axon regeneration in vivo, an effect that was also dependent on protrudin. These results demonstrate that RTN3 enhances neurite outgrowth/axon regeneration in a protrudin-dependent manner after both spinal cord and optic nerve injury.


Assuntos
Axônios/metabolismo , Proteínas de Transporte/metabolismo , Gânglios Espinais/metabolismo , Regeneração Nervosa , Crescimento Neuronal , Traumatismos do Nervo Óptico/metabolismo , Células Ganglionares da Retina/metabolismo , Traumatismos da Medula Espinal/metabolismo , Animais , Axônios/patologia , Comportamento Animal , Proteínas de Transporte/genética , Células Cultivadas , Modelos Animais de Doenças , Feminino , Gânglios Espinais/patologia , Atividade Motora , Traumatismos do Nervo Óptico/genética , Traumatismos do Nervo Óptico/patologia , Traumatismos do Nervo Óptico/fisiopatologia , Ratos Sprague-Dawley , Células Ganglionares da Retina/patologia , Transdução de Sinais , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Regulação para Cima , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo
19.
J Neurosci ; 41(39): 8210-8219, 2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34408066

RESUMO

Different types of tissue injury, such as inflammatory and neuropathic conditions, cause modality-specific alternations on temperature perception. There are profound changes in peripheral sensory neurons after injury, but how patterned neuronal activities in the CNS encode injury-induced sensitization to temperature stimuli is largely unknown. Using in vivo calcium imaging and mouse genetics, we show that formalin- and prostaglandin E2-induced inflammation dramatically increase spinal responses to heating and decrease responses to cooling in male and female mice. The reduction of cold response is largely eliminated on ablation of TRPV1-expressing primary sensory neurons, indicating a crossover inhibition of cold response from the hyperactive heat inputs in the spinal cord. Interestingly, chemotherapy medication oxaliplatin can rapidly increase spinal responses to cooling and suppress responses to heating. Together, our results suggest a push-pull mechanism in processing cold and heat inputs and reveal a synergic mechanism to shift thermosensation after injury.SIGNIFICANCE STATEMENT In this paper, we combine our novel in vivo spinal cord two-photon calcium imaging, mouse genetics, and persistent pain models to study how tissue injury alters the sensation of temperature. We discover modality-specific changes of spinal temperature responses in different models of injury. Chemotherapy medication oxaliplatin leads to cold hypersensitivity and heat hyposensitivity. By contrast, inflammation increases heat sensitivity and decreases cold sensitivity. This decrease in cold sensitivity results from the stronger crossover inhibition from the hyperactive heat inputs. Our work reveals the bidirectional change of thermosensitivity by injury and suggests that the crossover inhibitory circuit underlies the shifted thermosensation, providing a mechanism to the biased perception toward a unique thermal modality that was observed clinically in chronic pain patients.


Assuntos
Hiperalgesia/fisiopatologia , Células Receptoras Sensoriais/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/fisiopatologia , Sensação Térmica/fisiologia , Animais , Antineoplásicos/farmacologia , Cálcio/metabolismo , Formaldeído/farmacologia , Camundongos , Camundongos Transgênicos , Oxaliplatina/farmacologia , Células Receptoras Sensoriais/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Temperatura , Sensação Térmica/efeitos dos fármacos
20.
Spinal Cord Ser Cases ; 7(1): 58, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34257266

RESUMO

STUDY DESIGN: Focused literature review. OBJECTIVES: Objective of the study was to perform a literature search and summarise the clinical features and prognosis of persons with spinal cord injury (SCI) infected with COVID-19 from the published articles. SETTING: India. METHODS: PubMed, CENTRAL and MEDLINE were systematically searched using specific keywords. The study assessed 2747 scientific studies involving COVID-19 and SCI for possible inclusion in a meta-analysis of SCI and SARS-COV-2. Studies involving persons with SCI who were tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in the nasopharyngeal or throat swab polymerase chain reaction were included. RESULTS: Out of 2747 articles, 11 articles (206 participants), including six case reports, were included in this review. Fever was the most frequently observed symptom of COVID-19 infection in the SCI population. C-reactive protein (CRP) and lymphocytopenia were common abnormal laboratory parameters. The most common radiological finding in COVID-19 infection was ground glass opacities in lung fields. Prophylactic/therapeutic anticoagulation was given in a significant number of SCI persons infected with COVID-19. Persons with SCI who were diagnosed early showed good outcomes. CONCLUSIONS: Based on the few studies published on COVID-19 and SCI populations since 2019, this study determined fever, elevated CRP, lymphocytopenia and ground glass opacities, which indicated inflammation, compromised immune response, and lung edema, as the main clinical features of COVID-19 infection in SCI population. Though COVID-19 infection reported an increased number of deaths in few studies, a significant number of SCI populations with positive RT-PCR were treated successfully and discharged at home.


Assuntos
COVID-19/complicações , COVID-19/fisiopatologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/fisiopatologia , Humanos , Prognóstico
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