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2.
Science ; 370(6512)2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33004487

RESUMO

Injuries to the central nervous system (CNS) are inefficiently repaired. Resident neural stem cells manifest a limited contribution to cell replacement. We have uncovered a latent potential in neural stem cells to replace large numbers of lost oligodendrocytes in the injured mouse spinal cord. Integrating multimodal single-cell analysis, we found that neural stem cells are in a permissive chromatin state that enables the unfolding of a normally latent gene expression program for oligodendrogenesis after injury. Ectopic expression of the transcription factor OLIG2 unveiled abundant stem cell-derived oligodendrogenesis, which followed the natural progression of oligodendrocyte differentiation, contributed to axon remyelination, and stimulated functional recovery of axon conduction. Recruitment of resident stem cells may thus serve as an alternative to cell transplantation after CNS injury.


Assuntos
Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia , Oligodendroglia/fisiologia , Regeneração da Medula Espinal/fisiologia , Animais , Astrócitos/fisiologia , Axônios/fisiologia , Linhagem da Célula , Epêndima/citologia , Epêndima/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurogênese/genética , Fator de Transcrição 2 de Oligodendrócitos/metabolismo , Oligodendroglia/citologia , Recuperação de Função Fisiológica/genética , Recuperação de Função Fisiológica/fisiologia , Remielinização/genética , Remielinização/fisiologia , Análise de Célula Única , Traumatismos da Medula Espinal/fisiopatologia , Regeneração da Medula Espinal/genética
3.
Nat Commun ; 11(1): 5209, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060602

RESUMO

Chronic high-thoracic and cervical spinal cord injury (SCI) results in a complex phenotype of cardiovascular consequences, including impaired left ventricular (LV) contractility. Here, we aim to determine whether such dysfunction manifests immediately post-injury, and if so, whether correcting impaired contractility can improve spinal cord oxygenation (SCO2), blood flow (SCBF) and metabolism. Using a porcine model of T2 SCI, we assess LV end-systolic elastance (contractility) via invasive pressure-volume catheterization, monitor intraparenchymal SCO2 and SCBF with fiberoptic oxygen sensors and laser-Doppler flowmetry, respectively, and quantify spinal cord metabolites with microdialysis. We demonstrate that high-thoracic SCI acutely impairs cardiac contractility and substantially reduces SCO2 and SCBF within the first hours post-injury. Utilizing the same model, we next show that augmenting LV contractility with the ß-agonist dobutamine increases SCO2 and SCBF more effectively than vasopressor therapy, whilst also mitigating increased anaerobic metabolism and hemorrhage in the injured cord. Finally, in pigs with T2 SCI survived for 12 weeks post-injury, we confirm that acute hemodynamic management with dobutamine appears to preserve cardiac function and improve hemodynamic outcomes in the chronic setting. Our data support that cardio-centric hemodynamic management represents an advantageous alternative to the current clinical standard of vasopressor therapy for acute traumatic SCI.


Assuntos
Coração/fisiopatologia , Hemodinâmica/fisiologia , Hemorragia/fisiopatologia , Fenômenos Fisiológicos Respiratórios , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/fisiopatologia , Animais , Modelos Animais de Doenças , Dobutamina/farmacologia , Feminino , Fluxometria por Laser-Doppler , Chaperonas Moleculares/metabolismo , Norepinefrina/farmacologia , Fluxo Sanguíneo Regional/fisiologia , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Suínos , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/fisiopatologia
4.
Spinal Cord Ser Cases ; 6(1): 87, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943611

RESUMO

INTRODUCTION: Respiratory complications (RC) are a leading cause of death after spinal cord injury (SCI) due to compromised immune function and respiratory muscle weakness. Thus, individuals with SCI are at high risk of developing COVID-19 related RC. Results of a SCI clinical trial showed a supervised respiratory muscle training (RMT) program decreased risk of developing RC. The feasibility of conducting unsupervised RMT is not well documented. Four publications (n = 117) were identified in which unsupervised RMT was performed. Significant improvements in respiratory outcomes were reported in two studies: Maximal Inspiratory and Expiratory Pressure (MIP40% and MEP25%, respectively), Peak Expiratory Flow (PEF9%), seated and supine Forced Vital Capacity (FVC23% and 26%, respectively), and Peak Cough Flow (28%). This review and case report will attempt to show that an inspiratory muscle training (IMT) home exercise program (HEP) is feasible and may prepare the respiratory system for RC associated with COVID-19 in patients with SCI. CASE PRESENTATION: A 23-year-old with tetraplegia (P1), history of mechanical ventilation, and hospitalization for RC, completed 27 IMT HEP sessions in one month. MIP and sustained MIP (SMIP) increased from baseline by 28% and 26.5%, respectively. Expiratory volumes and rates also improved (FVC, FEV1, and PEF: 11.7%, 8.3%, and 14.2%, respectively). DISCUSSION: The effects of COVID-19 on patients with SCI remains inconclusive, but recent literature and the results of this case suggest that unsupervised IMT is feasible and may limit the severity of RC in patients with SCI who contract COVID-19.


Assuntos
Betacoronavirus , Exercícios Respiratórios/métodos , Infecções por Coronavirus/prevenção & controle , Inalação/fisiologia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Infecções Respiratórias/prevenção & controle , Traumatismos da Medula Espinal/terapia , Infecções por Coronavirus/fisiopatologia , Humanos , Masculino , Pneumonia Viral/fisiopatologia , Quadriplegia/complicações , Quadriplegia/fisiopatologia , Quadriplegia/terapia , Infecções Respiratórias/fisiopatologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/fisiopatologia , Adulto Jovem
5.
Ideggyogy Sz ; 73(7-08): 269-273, 2020 Jul 30.
Artigo em Húngaro | MEDLINE | ID: mdl-32750244

RESUMO

A 21 year female polytraumatized patient was admitted to our unit after a serious motorbike accident. We carried out CT imaging, which confirmed the fracture of the C-II vertebra and compression of spinal cord. Futhermore, the diagnostic investigations detected the compound and comminuted fracture of the left humerus and femur; the sacrum and the pubic bones were broken as well. After the stabilization of the cervical vertebra, a tracheotomy and the fixation of her limbs were performed. She spent 1.5 years in our unit. Meanwhile we tried to fix all the medical problems related to tetraplegia and respiratory insufficiency. As part of this process she underwent an electrophysiological examination in Uppsala (Sweden) and a diaphragm pacemaker was implanted. Our main goal was to reach the fully available quality of life. It is worth making this case familiar in a wider range of public as it could be an excellent example for the close collaboration of medical and non-medical fields.


Assuntos
Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/lesões , Diafragma/diagnóstico por imagem , Quadriplegia/reabilitação , Insuficiência Respiratória/terapia , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/terapia , Tomografia Computadorizada por Raios X/métodos , Cuidados Críticos , Feminino , Humanos , Quadriplegia/etiologia , Quadriplegia/fisiopatologia , Qualidade de Vida , Traumatismos da Medula Espinal/fisiopatologia , Traqueotomia , Resultado do Tratamento , Adulto Jovem
6.
Spinal Cord Ser Cases ; 6(1): 69, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32753638

RESUMO

STUDY DESIGN: Observational case-control study. OBJECTIVE: Individuals with spinal cord injury (SCI) develop systemic physiological changes that could increase the risk of severe evolution of coronavirus disease 2019 (COVID-19) and result in atypical clinical features of COVID-19 with possible delay in both diagnosis and treatment. We evaluated differences in clinical features and evolution of COVID-19 between people with SCI and able-bodied individuals. SETTING: The study was conducted in an Italian inpatient rehabilitation referral center for individuals with SCI during the lockdown for the COVID-19 pandemic. METHODS: We compared clinical information between patients with SCI and able-bodied healthcare workers of the same center who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the nasopharyngeal swab polymerase chain reaction. RESULTS: Overall, 15 out of the 25 SCI patients admitted to the center and 17 out of the 69 healthcare workers tested positive for SARS-CoV-2. Patients with SCI exhibited a significantly more advanced age and a higher prevalence of comorbidities. Nevertheless, no significant differences in clinical expression of COVID-19 and treatment strategies were observed between the two groups. All hospitalized subjects were treated in nonintensive care units and no deaths occurred in either group. CONCLUSIONS: This study does not support the supposed notion that COVID-19 could exhibit atypical clinical features or a worse evolution in the frail population of people with SCI.


Assuntos
Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Infecções por Coronavirus/terapia , Hidroxicloroquina/uso terapêutico , Oxigenoterapia , Pneumonia Viral/terapia , Traumatismos da Medula Espinal/fisiopatologia , Adulto , Idoso , Azitromicina/uso terapêutico , Betacoronavirus , Estudos de Casos e Controles , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Combinação de Medicamentos , Inibidores Enzimáticos/uso terapêutico , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Itália , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Prognóstico , Centros de Reabilitação , Ritonavir/uso terapêutico , Traumatismos da Medula Espinal/complicações
7.
Medicine (Baltimore) ; 99(29): e21188, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702880

RESUMO

Retrospective single institution observational study.The aim of the present study was to analyze the influence of early extensive posterior decompression on complications in patients with severe traumatic cervical spinal cord injury (tcSCI).Cervical SCI is associated with a high prevalence of hyponatremia and cardiopulmonary dysfunction. However, very few studies have focused on this exploration to reduce the incidence of SCI early complications.We reviewed the medical records of consecutive patients undergoing extensive posterior decompression within 24 h for severe tcSCI (American Spinal Injury Association Impairment Scale [AIS] A to C) admitted between January 2009 and January 2018. The data collected retrospectively included age, gender, mechanism, and level of SCI, AIS grade, fracture or dislocation, electrolyte, and cardiopulmonary complications.Of the 97 enrolled patients, the baseline AIS grade was AIS A in 14, AIS B in 31, and AIS C in 52. Improvement of at least two AIS grades was found in 26 (26.8%), and improvement of at least one grade was found in 80.4% of patients at discharge. Twenty-nine (29.9%) patients had mild hyponatremia, 8 (8.2%) had moderate hyponatremia, and 3 (3.1%) had severe hyponatremia during hospitalization. The incidences of hyponatremia, hypotension, and tracheotomy were 41.2%, 13.4%, and 6.2%, respectively. The mean forced vital capacity (FVC) on admission and at discharge was 1.34 ±â€Š0.46 L and 2.21 ±â€Š0.41 L (P < .0001), respectively. Five patients developed pneumonia.Our results suggest that early expansive posterior decompression significantly reduces the incidence of hyponatremia, hypotension, and tracheotomy by promoting recovery of spinal cord function after severe tcSCI.


Assuntos
Medula Cervical/fisiopatologia , Descompressão Cirúrgica/reabilitação , Hiponatremia/etiologia , Traumatismos da Medula Espinal/cirurgia , Disfunção Ventricular/etiologia , Adulto , Medula Cervical/lesões , Medula Cervical/cirurgia , Descompressão Cirúrgica/métodos , Descompressão Cirúrgica/estatística & dados numéricos , Feminino , Humanos , Hiponatremia/sangue , Hiponatremia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Estudos Retrospectivos , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/fisiopatologia , Resultado do Tratamento , Disfunção Ventricular/fisiopatologia
8.
PLoS One ; 15(7): e0236050, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32678832

RESUMO

Neurotrophic factors have been regarded having promising potentials for neuronal protection and regeneration, and thus promoting beneficial effects of kinesiological functions. They can be suspected to play important roles in cell/tissue grafting for various neural diseases. The clinical applications of such trophic factors to the central nervous system (CNS), however, have caused problematic side effects on account of the distinctive bioactive properties. In the course of developing synthetic compounds reflecting beneficial properties of basic fibroblast growth factor (bFGF), we conducted screening candidates that stimulate to trigger the intracellular tyrosine phosphorylation of FGF receptor and lead to the subsequent intracellular signaling in neurons. A small synthetic molecule SUN13837 was characterized by mimicking the beneficial properties of bFGF, which have been known as its specific activities when applied to CNS. What is more remarkable is that SUN13837 is eliminated the bioactivity to induce cell proliferation of non-neuronal somatic cells. On the bases of studies of pharmacology, behavior, physiology and histology, the present study reports that SUN13837 is characterized as a promising synthetic compound for treatment of devastating damages onto the rat spinal cord.


Assuntos
Materiais Biomiméticos/farmacologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Axônios/efeitos dos fármacos , Axônios/fisiologia , Feminino , Crescimento Neuronal/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Regeneração/efeitos dos fármacos , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia
9.
PLoS One ; 15(7): e0236490, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716921

RESUMO

Individuals with spinal cord injury develop cardiovascular disease more than age-matched, non-injured cohorts. However, progression of systolic and diastolic dysfunction into cardiovascular disease after spinal cord injury is not well described. We sought to investigate the relationship between systolic and diastolic function in chronic spinal cord injury to describe how biological sex, level, severity, and duration of injury correlate with structural changes in the left ventricle. Individuals with chronic spinal cord injury participated in this study (n = 70). Registered diagnostic cardiac sonographers used cardiac ultrasound to measure dimensions, mass, and systolic and diastolic function of the left ventricle. We found no significant relationship to severity or duration of injury with left ventricle measurements, systolic function outcome, or diastolic function outcome. Moreover, nearly all outcomes measured were within the American Society of Echocardiography-defined healthy range. Similar to non-injured individuals, when indexed by body surface area (BSA) left ventricle mass [-14 (5) g/m2, p < .01], end diastolic volume [-6 (3) mL/m2, p < .05], and end systolic volume [-4 (1) mL/m2, p < .01] were significantly decreased in women compared with men. Likewise, diastolic function outcomes significantly worsened with age: E-wave velocity [-5 (2), p < .01], E/A ratio [-0.23 (0.08), p < .01], and e' velocity [lateral: -1.5 (0.3) cm/s, p < .001; septal: -0.9 (0.2), p < .001] decreased with age while A-wave velocity [5 (1) cm/s, p < .001] and isovolumic relaxation time [6 (3) ms, p < .05] increased with age. Women demonstrated significantly decreased cardiac size and volumes compared with men, but there was no biological relationship to dysfunction. Moreover, individuals were within the range of ASE-defined healthy values with no evidence of systolic or diastolic function and no meaningful relationship to level, severity, or duration of injury. Decreases to left ventricular dimensions and mass seen in spinal cord injury may result from adaptation rather than maladaptive myocardial remodeling, and increased incidence of cardiovascular disease may be related to modifiable risk factors.


Assuntos
Diástole/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Sístole/fisiologia , Adulto , Pressão Sanguínea , Feminino , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Análise Multivariada , Tamanho do Órgão
10.
BMC Neurol ; 20(1): 273, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641012

RESUMO

BACKGROUND: Restoring community walking remains a highly valued goal for persons recovering from traumatic incomplete spinal cord injury (SCI). Recently, studies report that brief episodes of low-oxygen breathing (acute intermittent hypoxia, AIH) may serve as an effective plasticity-inducing primer that enhances the effects of walking therapy in persons with chronic (> 1 year) SCI. More persistent walking recovery may occur following repetitive (weeks) AIH treatment involving persons with more acute SCI, but this possibility remains unknown. Here we present our clinical trial protocol, designed to examine the distinct influences of repetitive AIH, with and without walking practice, on walking recovery in persons with sub-acute SCI (< 12 months) SCI. Our overarching hypothesis is that daily exposure (10 sessions, 2 weeks) to AIH will enhance walking recovery in ambulatory and non-ambulatory persons with subacute (< 12 months) SCI, presumably by harnessing endogenous mechanisms of plasticity that occur soon after injury. METHODS: To test our hypothesis, we are conducting a randomized, placebo-controlled clinical trial on 85 study participants who we stratify into two groups according to walking ability; those unable to walk (non-ambulatory group) and those able to walk (ambulatory group). The non-ambulatory group receives either daily AIH (15, 90s episodes at 10.0% O2 with 60s intervals at 20.9% O2) or daily SHAM (15, 90s episodes at 20.9% O2 with 60s intervals at 20.9% O2) intervention. The ambulatory group receives either 60-min walking practice (WALK), daily AIH + WALK, or daily SHAM+WALK intervention. Our primary outcome measures assess overground walking speed (10-Meter Walk Test), endurance (6-Minute Walk Test), and balance (Timed Up & Go Test). For safety, we also measure levels of pain, spasticity, systemic hypertension, and autonomic dysreflexia. We record outcome measures at baseline, days 5 and 10, and follow-ups at 1 week, 1 month, 6 months, and 12 months post-treatment. DISCUSSION: The goal of this clinical trial is to reveal the extent to which daily AIH, alone or in combination with task-specific walking practice, safely promotes persistent recovery of walking in persons with traumatic, subacute SCI. Outcomes from this study may provide new insight into ways to enhance walking recovery in persons with SCI. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02632422 . Registered 16 December 2015.


Assuntos
Terapia por Exercício , Hipóxia , Traumatismos da Medula Espinal/fisiopatologia , Caminhada/fisiologia , Método Duplo-Cego , Humanos , Dor/etiologia , Recuperação de Função Fisiológica
11.
PLoS One ; 15(6): e0234245, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32542053

RESUMO

There are approximately 1.2 million people currently living with spinal cord injury (SCI), with a majority of cases at the cervical level and half involving incomplete injuries. Yet, as most preclinical research has been focused on bilateral thoracic models, there remains a disconnect between bench and bedside that limits translational success. Here, we profile a clinically relevant model of unilateral cervical contusion injury in the mouse (30kD with 0, 2, 5, or 10 second dwell time). We demonstrate sustained behavioral deficits in performance on grip strength, cylinder reaching, horizontal ladderbeam and CatWalk automated gait analysis tasks. Beyond highlighting reliable parameters for injury assessment, we also explored the effect of mouse strain and age on injury outcome, including evaluation of constitutively immunodeficient mice relevant for neurotransplantation and cellular therapy testing. Comparison of C57Bl/6 and immunodeficient Rag2gamma(c)-/- as well as Agouti SCIDxRag2Gamma(c)-/- hybrid mouse strains revealed fine differences in post-injury ipsilateral grip strength as well as total number of rearings on the cylinder task. Differences in post-SCI contralateral forepaw duty cycle and regularity index as measured by CatWalk gait analysis between the two immunodeficient strains were also observed. Further, assessment of young (3-4 months old) and aging (16-17 months old) Rag2gamma(c)-/- mice identified age-related pre-injury differences in strength and rearing that were largely masked following cervical contusion injury; observations that may help interpret previous results in aged rodents as well as human clinical trials. Collectively, the work provides useful insight for experimental design and analysis of future pre-clinical studies in a translational unilateral cervical contusion injury model.


Assuntos
Envelhecimento , Vértebras Cervicais/lesões , Contusões , Traumatismos da Medula Espinal , Animais , Contusões/metabolismo , Contusões/patologia , Contusões/fisiopatologia , Modelos Animais de Doenças , Feminino , Camundongos , Análise Multivariada , Neuroquímica , Recuperação de Função Fisiológica , Especificidade da Espécie , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia
12.
Neurology ; 95(7): e805-e814, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32591473

RESUMO

OBJECTIVE: To determine whether cervical cord levels of metabolites are associated with pain sensation after spinal cord injury (SCI) by performing magnetic resonance spectroscopy in patients with SCI with and without neuropathic pain (NP). METHODS: Cervical cord single-voxel spectroscopic data of 24 patients with SCI (14 with NP, 10 pain-free) and 21 healthy controls were acquired at C2/3 to investigate metabolite ratios associated with neuroinflammation (choline-containing compounds to myoinositol [tCho/mI]) and neurodegeneration (total N-acetylaspartate to myo-inositol [tNAA/mI]). NP levels were measured, and Spearman correlation tests assessed associations between metabolite levels, cord atrophy, and pinprick score. RESULTS: In patients with NP, tCho/mI levels were increased (p = 0.024) compared to pain-free patients and negatively related to cord atrophy (p = 0.006, r = 0.714). Better pinprick score was associated with higher tCho/mI levels (p = 0.032, r = 0.574). In pain-free patients, tCho/mI levels were not related to cord atrophy (p = 0.881, r = 0.055) or pinprick score (p = 0.676, r = 0.152). tNAA/mI levels were similar in both patient groups (p = 0.396) and were not associated with pinprick score in patients with NP (p = 0.405, r = 0.242) and pain-free patients (p = 0.117, r = 0.527). CONCLUSIONS: Neuroinflammatory metabolite levels (i.e., tCho/mI) were elevated in patients with NP, its magnitude being associated with less cord atrophy and greater pain sensation (e.g., pinprick score). This suggests that patients with NP have more residual spinal tissue and greater metabolite turnover than pain-free patients. Neurodegenerative metabolite levels (i.e., tNAA/mI) were associated with greater cord atrophy but unrelated to NP. Identifying the metabolic NP signature provides new NP treatment targets and could improve patient stratification in interventional trials. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that levels of magnetic resonance spectroscopy-identified metabolites of neuroinflammation were elevated in patients with SCI with NP compared to those without NP.


Assuntos
Medula Cervical/metabolismo , Inflamação/metabolismo , Neuralgia/metabolismo , Traumatismos da Medula Espinal/metabolismo , Adulto , Atrofia/patologia , Medula Cervical/patologia , Colina/metabolismo , Creatina/metabolismo , Feminino , Humanos , Inflamação/complicações , Inositol/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neuralgia/complicações , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/fisiopatologia
13.
BMC Neurol ; 20(1): 236, 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32517723

RESUMO

BACKGROUND: Diffusion tensor imaging (DTI) is an effective method to identify subtle changes to normal-appearing white matter (WM). Here we analyzed the DTI data with other examinations, including motor evoked potentials (MEPs), histopathological images, and behavioral results, to reflect the lesion development in different degrees of spinal cord injury (SCI) in acute and subacute stages. METHOD: Except for 2 Sprague -Dawley rats which died from the anesthesia accident, the rest 42 female rats were randomized into 3 groups: control group (n = 6), moderate group (n = 18), and severe group (n = 18). Moderate (a 50-g aneurysm clip with 0.4-mm thickness spacer) or severe (a 50-g aneurysm clip with no spacer) contusion SCI at T8 vertebrae was induced. Then the electrophysiological assessments via MEPs, behavioral deterioration via the Basso, Beattie, and Bresnaha (BBB) scores, DTI data, and histopathology examination were analyzed. RESULTS: In this study, we found that the damage of WM myelin, MEPs amplitude, BBB scores and the decreases in the values of fractional anisotropy (FA) and axial diffusivity (AD) were more obvious in the severe injury group than those of the moderate group. Additionally, the FA and AD values could identify the extent of SCI in subacute and early acute SCI respectively, which was reflected in a robust correlations with MEPs and BBB scores. While the values of radial diffusivity (RD) showed no significant changes. CONCLUSIONS: Our data confirmed that DTI was a valuable in ex vivo imaging tool to identify damaged white matter tracts after graded SCI in rat, which may provide useful information for the early identification of the severity of SCI.


Assuntos
Imagem de Tensor de Difusão/métodos , Potencial Evocado Motor/fisiologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Anisotropia , Feminino , Ratos , Ratos Sprague-Dawley , Substância Branca/patologia , Substância Branca/fisiopatologia
14.
PLoS One ; 15(5): e0232975, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392241

RESUMO

Finite element models combined with animal experimental models of spinal cord injury provides the opportunity for investigating the effects of the injury mechanism on the neural tissue deformation and the resulting tissue damage. Thus, we developed a finite element model of the mouse cervical spinal cord in order to investigate the effect of morphological, experimental and mechanical factors on the spinal cord mechanical behavior subjected to transverse contusion. The overall mechanical behavior of the model was validated with experimental data of unilateral cervical contusion in mice. The effects of the spinal cord material properties, diameter and curvature, and of the impactor position and inclination on the strain distribution were investigated in 8 spinal cord anatomical regions of interest for 98 configurations of the model. Pareto analysis revealed that the material properties had a significant effect (p<0.01) for all regions of interest of the spinal cord and was the most influential factor for 7 out of 8 regions. This highlighted the need for comprehensive mechanical characterization of the gray and white matter in order to develop effective models capable of predicting tissue deformation during spinal cord injuries.


Assuntos
Modelos Neurológicos , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Fenômenos Biomecânicos , Simulação por Computador , Modelos Animais de Doenças , Análise de Elementos Finitos , Substância Cinzenta/patologia , Substância Cinzenta/fisiopatologia , Humanos , Imageamento Tridimensional , Camundongos , Traumatismos da Medula Espinal/etiologia , Substância Branca/patologia , Substância Branca/fisiopatologia
15.
Urologe A ; 59(9): 1076-1081, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32424576

RESUMO

BACKGROUND: Nearly all patients with spinal cord injury (SCI) suffer from neurogenic lower urinary tract dysfunction (NLUTD). Untreated NLUTD is a risk factor for renal damage and can significantly affect quality of life (QoL). Patients with SCI frequently use complementary medicine to alleviate symptoms, namely for urologic problems. OBJECTIVES: We evaluated whether homeopathic treatment influences objective urodynamic parameters. MATERIALS AND METHODS: In a retrospective study, urodynamic data of patients with NLUTD due to SCI who received constitutional homeopathic treatment by the consultants of our hospital were evaluated before initiation of homeopathic treatment and at the most recent follow-up. Modifications in urologic treatment were taken into account. RESULTS: Urodynamic results from 35 patients who underwent homeopathic treatment (14 women, 21 men, median age 46 years, tetraplegia: n = 14; paraplegia: n = 21) were available at both time points and could therefore be evaluated. In all, 20 patients used intermittent catheterization, 6 persons had an indwelling catheter, and 9 persons emptied their bladders without a catheter. There were no significant differences in the urodynamic parameters before and during treatment. Changes in urologic therapy correlated with significant improvement in urodynamic findings. CONCLUSIONS: As all patients were under urologic surveillance, and immediate urologic treatment was established if necessary, a retrospective study design proved not to be suitable to detect possible influences of homeopathic treatment on urodynamic parameters in patients with SCI. Thus, a prospective randomized study is essential.


Assuntos
Sintomas do Trato Urinário Inferior/etiologia , Traumatismos da Medula Espinal/complicações , Bexiga Urinaria Neurogênica/etiologia , Urodinâmica/fisiologia , Adulto , Idoso , Feminino , Humanos , Sintomas do Trato Urinário Inferior/fisiopatologia , Sintomas do Trato Urinário Inferior/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Traumatismos da Medula Espinal/fisiopatologia , Bexiga Urinaria Neurogênica/fisiopatologia , Bexiga Urinaria Neurogênica/terapia
16.
Life Sci ; 254: 117796, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32417375

RESUMO

AIMS: To explore the possible mechanism that microRNA-223 regulates the spinal cord injury as well as the posttranscriptional control of genes after spinal injury. MATERIALS AND METHODS: Rats contusion spinal cord injury model and microglia model were established and examined by pathological test and the inflammatory cytokines levels were evaluated by RT-PCR. Then microRNA-223 was overexpressed in spinal cord to see the impact on rats with spinal cord injury. The overexpression of microRNA-223 in microglia stimulated by LPS was used to assess the inflammation. Then bioinformatic method combined with luciferase reporter genes were used to detect the target gene of microRNA-223. Then NLRP3, one of the target genes of microRNA-223 were regulated to see the impact on microglia as well as spinal injury rats. KEY FINDINGS: It showed that microRNA-223 increased after acute spinal injury. However, the suppression of microRNA-223 aggravated the spinal injury as well as the inflammation while the over-expression of microRNA-223 alleviated the spinal injury to some extent, decreased the inflammation and improved nervous system function. In vitro, it was found that the over-expression of microRNA-223 in microglia suppressed inflammation induced by LPS and vice versa. NLRP3 was found the target of microRNA-223. The up-regulation of NLRP3 could diminish the effects of microRNA-223 and aggravated inflammation in microglia. SIGNIFICANCE: The over-expression of microRNA-223 alleviated the inflammation and improved neuron function. NLRP3 was the downstream target of microRNA-223, the overexpression of which led to severe inflammation in microglia.


Assuntos
Inflamação/prevenção & controle , MicroRNAs/fisiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Animais , Citocinas/metabolismo , Inflamação/complicações , Lipopolissacarídeos , MicroRNAs/biossíntese , Microglia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Cultura Primária de Células , Ratos , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia
17.
Muscle Nerve ; 61(6): 708-718, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32413247

RESUMO

The loss of upper limb motor function can have a devastating effect on people's lives. To restore upper limb control and functionality, researchers and clinicians have developed interfaces to interact directly with the human body's motor system. In this invited review, we aim to provide details on the peripheral nerve interfaces and brain-machine interfaces that have been developed in the past 30 years for upper extremity control, and we highlight the challenges that still remain to transition the technology into the clinical market. The findings show that peripheral nerve interfaces and brain-machine interfaces have many similar characteristics that enable them to be concurrently developed. Decoding neural information from both interfaces may lead to novel physiological models that may one day fully restore upper limb motor function for a growing patient population.


Assuntos
Amputados/reabilitação , Pesquisa Biomédica/tendências , Robótica/tendências , Traumatismos da Medula Espinal/reabilitação , Extremidade Superior/fisiologia , Pesquisa Biomédica/métodos , Interfaces Cérebro-Computador/tendências , Previsões , Humanos , Robótica/métodos , Traumatismos da Medula Espinal/fisiopatologia
18.
Exerc Sport Sci Rev ; 48(3): 125-132, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32412926

RESUMO

Acute intermittent hypoxia (AIH) and task-specific training (TST) synergistically improve motor function after spinal cord injury; however, mechanisms underlying this synergistic relation are unknown. We propose a hypothetical working model of neural network and cellular elements to explain AIH-TST synergy. Our goal is to forecast experiments necessary to advance our understanding and optimize the neurotherapeutic potential of AIH-TST.


Assuntos
Terapia por Exercício/métodos , Neurônios Motores/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/reabilitação , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Humanos , Hipóxia/fisiopatologia , Glicoproteínas de Membrana/metabolismo , Plasticidade Neuronal , Receptor trkB/metabolismo , Medula Espinal/metabolismo
19.
J Vis Exp ; (157)2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32281968

RESUMO

Incomplete spinal cord injury (SCI) often leads to impairments of sensorimotor functions and is clinically the most frequent type of SCI. Human Brown-Séquard syndrome is a common type of incomplete SCI caused by a lesion to one half of the spinal cord which results in paralysis and loss of proprioception on the same (or ipsilesional) side as the injury, and loss of pain and temperature sensation on the opposite (or contralesional) side. Adequate methodologies for producing a spinal cord lateral hemisection (HX) and assessing neurological impairments are essential to establish a reliable animal model of Brown-Séquard syndrome. Although lateral hemisection model plays a pivotal role in basic and translational research, standardized protocols for creating such a hemisection and assessing unilateralized function are lacking. The goal of this study is to describe step-by-step procedures to produce a rat spinal lateral HX at the 9th thoracic (T9) vertebral level. We, then, describe a combined behavior scale for HX (CBS-HX) that provides a simple and sensitive assessment of asymmetric neurological performance for unilateral SCI. The CBS-HX, ranging from 0 to 18, is composed of 4 individual assessments which include unilateral hindlimb stepping (UHS), coupling, contact placing, and grid walking. For CBS-HX, the ipsilateral and contralateral hindlimbs are assessed separately. We found that, after a T9 HX, the ipsilateral hindlimb showed impaired behavior function whereas the contralateral hindlimb showed substantial recovery. The CBS-HX effectively discriminated behavioral functions between ipsilateral and contralateral hindlimbs and detected temporal progression of recovery of the ipsilateral hindlimb. The CBS-HX components can be analyzed separately or in combination with other measures when needed. Although we only provided visual descriptions of the surgical procedures and behavioral assessments of a thoracic HX, the principle may be applied to other incomplete SCIs and at other levels of the injury.


Assuntos
Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/cirurgia , Animais , Comportamento Animal , Modelos Animais de Doenças , Masculino , Ratos , Medula Espinal/patologia
20.
Lasers Med Sci ; 35(8): 1751-1758, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32337679

RESUMO

Complete or incomplete spinal cord injury (SCI) results in permanent neurological deficits due to the interruption of nerve impulses, causing the loss of motor and sensory function, which leads to a reduction in quality of life. The focus of rehabilitation for such individuals is to improve quality of life and promote functional recovery. Photobiomodulation (PBM) has proved to be promising complementary treatment in cases of SCI. The aim of the present study was to investigate the effects of PBM combined with physiotherapy on sensory-motor responses below the level of the injury and quality of life in individuals with SCI. Thirty participants were randomized for allocation to the PBM group (active PBM + physiotherapy) or sham group (sham PBM + physiotherapy). Physiotherapy was administered three times a week. Sensitivity and motor skills were evaluated using the ASIA impairment scale. Quality of life was assessed using the WHOQOL-BREF questionnaire. The data were analyzed with the level of significance set to 5%. Improvements in sensitivity and an increase in the perception of muscle contraction were found in the active PBM group 30 days after treatment compared with the sham group. The results of the WHOQOL-BREF questionnaire revealed a significant difference in general quality of life favoring the active PBM group over the sham group after treatment. Physiotherapy combined with PBM leads to better sensory-motor recovery in patients with SCI as well as a better perception of health and quality of life. Trial registration identifier: NCT03031223.


Assuntos
Terapia com Luz de Baixa Intensidade , Atividade Motora/efeitos da radiação , Modalidades de Fisioterapia , Sensação/efeitos da radiação , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular/efeitos da radiação , Qualidade de Vida , Recuperação de Função Fisiológica/efeitos da radiação , Traumatismos da Medula Espinal/radioterapia , Adulto Jovem
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