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1.
Anesthesiology ; 132(2): 253-266, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31939839

RESUMO

BACKGROUND: Cognitive changes after anesthesia and surgery represent a significant public health concern. We tested the hypothesis that, in patients 60 yr or older scheduled for noncardiac surgery, automated management of anesthetic depth, cardiac blood flow, and protective lung ventilation using three independent controllers would outperform manual control of these variables. Additionally, as a result of the improved management, patients in the automated group would experience less postoperative neurocognitive impairment compared to patients having standard, manually adjusted anesthesia. METHODS: In this single-center, patient-and-evaluator-blinded, two-arm, parallel, randomized controlled, superiority study, 90 patients having noncardiac surgery under general anesthesia were randomly assigned to one of two groups. In the control group, anesthesia management was performed manually while in the closed-loop group, the titration of anesthesia, analgesia, fluids, and ventilation was performed by three independent controllers. The primary outcome was a change in a cognition score (the 30-item Montreal Cognitive Assessment) from preoperative values to those measures 1 week postsurgery. Secondary outcomes included a battery of neurocognitive tests completed at both 1 week and 3 months postsurgery as well as 30-day postsurgical outcomes. RESULTS: Forty-three controls and 44 closed-loop patients were assessed for the primary outcome. There was a difference in the cognition score compared to baseline in the control group versus the closed-loop group 1 week postsurgery (-1 [-2 to 0] vs. 0 [-1 to 1]; difference 1 [95% CI, 0 to 3], P = 0.033). Patients in the closed-loop group spent less time during surgery with a Bispectral Index less than 40, had less end-tidal hypocapnia, and had a lower fluid balance compared to the control group. CONCLUSIONS: Automated anesthetic management using the combination of three controllers outperforms manual control and may have an impact on delayed neurocognitive recovery. However, given the study design, it is not possible to determine the relative contribution of each controller on the cognition score.


Assuntos
Anestesia Geral/métodos , Anestésicos Intravenosos/administração & dosagem , Cognição/fisiologia , Monitores de Consciência , Monitorização Intraoperatória/métodos , Recuperação de Função Fisiológica/fisiologia , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral/tendências , Cognição/efeitos dos fármacos , Monitores de Consciência/tendências , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Monitorização Intraoperatória/tendências , Recuperação de Função Fisiológica/efeitos dos fármacos
2.
Isr Med Assoc J ; 12(21): 812-816, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31814345

RESUMO

BACKGROUND: The effect of repeated intravenous amantadine (IVAM) in advanced Parkinsonism has not been studied in depth. OBJECTIVES: To report the experience of our medical center with repeated IVAM infusions in patients with advanced Parkinsonism. METHODS: Thirty patients with advanced Parkinsonism of various etiologies were enrolled in an open-label retrospective study. All patients were treated with IVAM infusions in a neurological daycare center. Treatment was initiated with a loading dose of 200/400 mg per day for 5 days followed by a once-daily maintenance dose of 200/400 mg every 1 to 3 weeks. Patients and their caregivers participated in a structured interview and independently completed a clinical global impression of changes scale questionnaire on various motor and non-motor symptoms. RESULTS: Patient mean age was 73.3 ± 9.7 years, average disease duration was 6.2 ± 5.7 years, and mean Hoehn and Yahr score was 3.2 ± 0.84. Mean duration of the IVAM treatment was 15.1 ± 11.6 months. An improvement in general function was reported by 91% of the patients and 89% of the caregivers. Most of the patients reported improvement in tremor and rigidity, as well as in gait stability, freezing of gait, and reduced falls. The treatment was safe with few side effects. CONCLUSIONS: Our data suggest that repeated IVAM infusions could be an effective treatment against various motor symptoms and for improvement of mobility in patients with advanced Parkinsonism. Further randomized clinical trials with a larger sample size using objective measures are warranted to validate our results.


Assuntos
Acidentes por Quedas/prevenção & controle , Amantadina , Destreza Motora/efeitos dos fármacos , Doença de Parkinson , Recuperação de Função Fisiológica/efeitos dos fármacos , Idoso , Amantadina/administração & dosagem , Amantadina/efeitos adversos , Progressão da Doença , Dopaminérgicos/administração & dosagem , Dopaminérgicos/efeitos adversos , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento
3.
Medicine (Baltimore) ; 98(39): e17358, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574881

RESUMO

OBJECTIVES: Previous studies comparing adductor canal block (ACB) with femoral nerve block (FNB) are inconclusive with regard to patient-controlled analgesia (PCA) induced by opioids. Moreover, some postoperative pain severity results differ between previous randomized controlled trials (RCTs). The primary aim of the current study was to compare total intravenous morphine consumption administered via PCA during the first postoperative day in continuous FNB and ACB groups after total knee arthroplasty (TKA). Secondary aims included evaluation of postoperative pain via a visual analog scale, degree of knee extension, quadriceps muscle strength, and ability to sit, stand upright, and walk. METHODS: The study was a RCT. Inclusion criteria were presence of gonarthrosis, age >18 and <75 years, and scheduled for TKA under single-shot spinal anesthesia. RESULTS: A number of morphine uses was lower in the FNB group than in the ACB group (14, range 12-15 vs 20, range 18-22; P = .0001), and they perceived less severe pain at the 8th (P = .00003) and 24th hours. However, ACB was significantly superior with regard to most of the other parameters pertaining to mobility, including muscle strength at the 8th and 24th hours, degree of knee extension at the 8th hour, sitting at the 8th hour, standing upright at the 24th hour, and walking at the 24th and 48th hours. DISCUSSION: FNB was associated with the perception of less severe pain after TKAs. However, ACB was associated with earlier mobility rehabilitation.


Assuntos
Artroplastia do Joelho/efeitos adversos , Nervo Femoral/efeitos dos fármacos , Bloqueio Nervoso/métodos , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Humanos , Masculino , Morfina/uso terapêutico , Força Muscular/efeitos dos fármacos , Medição da Dor , Dor Pós-Operatória/etiologia , Músculo Quadríceps , Amplitude de Movimento Articular/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Resultado do Tratamento
4.
Dis Colon Rectum ; 62(11): 1305-1315, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31567924

RESUMO

BACKGROUND: Delayed initiation of adjuvant chemotherapy negatively impacts long-term survival in patients with colorectal cancer. Colorectal enhanced recovery protocols result in decreased complications and length of stay; however, the impact of enhanced recovery on the timing of adjuvant chemotherapy remains unknown. OBJECTIVE: This study aimed to identify factors associated with on-time delivery of adjuvant chemotherapy after colorectal cancer surgery, hypothesizing that implementation of an enhanced recovery protocol would result in more patients receiving on-time chemotherapy. DESIGN: This was a retrospective cohort study comparing the rate of on-time adjuvant chemotherapy delivery after colorectal cancer resection before and after implementation of an enhanced recovery protocol. SETTINGS: The study was conducted at a large academic medical center. PATIENTS: All of the patients who underwent nonemergent colorectal cancer resections for curative intent from January 2010 to June 2017, excluding patients who had no indication for adjuvant chemotherapy, had received preoperative systemic chemotherapy, or did not have medical oncology records available were included. MAIN OUTCOME MEASURES: Patients before and enhanced recovery were compared, with the rate of on-time adjuvant chemotherapy delivery as the primary outcome. Adjuvant chemotherapy delivery was considered on time if initiated ≤8 weeks postoperatively, and treatment was considered delayed or omitted if initiated >8 weeks postoperatively (delayed) or never received (omitted). Multivariable logistic regression identified predictors of on-time chemotherapy delivery. RESULTS: A total of 363 patients met inclusion criteria, with 189 patients (52.1%) undergoing surgery after enhanced recovery implementation. Groups differed in laparoscopic approach and median procedure duration, both of which were higher after enhanced recovery. Significantly more patients received on-time chemotherapy after enhanced recovery implementation (p = 0.007). Enhanced recovery was an independent predictor of on-time adjuvant chemotherapy (p = 0.014). LIMITATIONS: The study was limited by its retrospective and nonrandomized before-and-after design. CONCLUSIONS: Enhanced recovery was associated with receiving on-time adjuvant chemotherapy. As prompt initiation of adjuvant chemotherapy improves survival in colorectal cancer, future investigation of long-term oncologic outcomes is necessary to evaluate the potential impact of enhanced recovery on survival. See Video Abstract at http://links.lww.com/DCR/B21. LA IMPLEMENTACIÓN DE UN PROTOCOLO DE RECUPERACIÓN ACELERADA SE ASOCIA CON EL INICIO A TIEMPO DE QUIMIOTERAPIA ADYUVANTE EN CÁNCER COLORRECTAL:: El inicio tardío de la quimioterapia adyuvante afecta negativamente la supervivencia a largo plazo en pacientes con cáncer colorrectal. Los protocolos de recuperación acelerada colorrectales dan lugar a una disminución de las complicaciones y la duración de estancia hospitalaria; sin embargo, el impacto de la recuperación acelerada en el momento de inicio de quimioterapia adyuvante sigue siendo desconocido.Este estudio tuvo como objetivo identificar los factores asociados con la administración a tiempo de la quimioterapia adyuvante después de la cirugía de cáncer colorrectal, con la hipótesis de que la implementación de un protocolo de recuperación acelerada daría lugar a que más pacientes reciban quimioterapia a tiempo.Estudio de cohorte retrospectivo que compara la tasa de administración de quimioterapia adyuvante a tiempo después de la resección del cáncer colorrectal antes y después de la implementación de un protocolo de recuperación acelerada.Centro médico académico grande.Todos los pacientes que se sometieron a resecciones de cáncer colorrectal no emergentes con intención curativa desde enero de 2010 hasta junio de 2017, excluyendo a los pacientes que no tenían indicación de quimioterapia adyuvante, que recibieron quimioterapia sistémica preoperatoria o no tenían registros médicos de oncología disponibles.Los pacientes se compararon antes y después de la implementación de la recuperación acelerada, con la tasa de administración de quimioterapia adyuvante a tiempo como el resultado primario. La administración de quimioterapia adyuvante se consideró a tiempo si se inició ≤8 semanas después de la operación, y el tratamiento se consideró retrasado / omitido si se inició> 8 semanas después de la operación (retrasado) o nunca fue recibido (omitido). La regresión logística multivariable identificó predictores de administración de quimioterapia a tiempo.363 pacientes cumplieron con los criterios de inclusión, con 189 (52.1%) pacientes sometidos a cirugía después de la implementación de recuperación acelerada. Los grupos difirieron en el abordaje laparoscópico y la duración media del procedimiento; ambos factores fueron mayores después de la recuperación acelerada. Significativamente más pacientes recibieron quimioterapia a tiempo después de la implementación de recuperación acelerada (p = 0.007). La recuperación acelerada fue un factor predictivo independiente de quimioterapia adyuvante a tiempo (p = 0.014).Diseño retrospectivo, tipo ¨antes y después¨ no aleatorizado.La recuperación acelerada se asoció con la recepción de quimioterapia adyuvante a tiempo. Debido a que el inicio rápido de la quimioterapia adyuvante mejora la supervivencia en el cáncer colorrectal, en el futuro será necesario investigar los resultados oncológicos a largo plazo para evaluar el impacto potencial de la recuperación acelerada en la supervivencia. Vea el Resumen en Video en http://links.lww.com/DCR/B21.


Assuntos
Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante/métodos , Colectomia/reabilitação , Neoplasias Colorretais , Complicações Pós-Operatórias/prevenção & controle , Recuperação de Função Fisiológica/efeitos dos fármacos , Sobreviventes/estatística & dados numéricos , Tempo para o Tratamento , Protocolos Clínicos/normas , Colectomia/métodos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/reabilitação , Neoplasias Colorretais/terapia , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tempo para o Tratamento/normas , Tempo para o Tratamento/estatística & dados numéricos , Estados Unidos/epidemiologia
5.
J Clin Neurosci ; 70: 61-66, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31606287

RESUMO

The use of anticoagulation and antiplatelet agents (ACAP) has steadily increased over recent years. However, the effects of ACAP on traumatic brain injuries (TBI) are not well investigated. The aim of this study was to investigate the effects of pre-injury ACAP use on clinical outcome and mortality in severe TBI. A retrospective case-control study was performed for all patients who presented with severe TBI (GCS < 8) to the National Neuroscience Institute, Singapore, between 2006 and 2009. Patients with pre-injury ACAP use were compared to matched controls. Outcome measures were mortality at 14 days and 6 months, and Glasgow Outcome Score (GOS) at 6 months using a sliding dichotomy approach. Univariate analysis was performed using Chi-square and student's t-test and logistic regression was used to model the effect of ACAP on mortality rate. Forty-five patients with pre-injury use of ACAP were compared with matched controls. The mortality at 14 days (OR = 0.5, 95% CI 0.2-1.4) and 6 months (OR = 0.7, 95% CI 0.2-1.9) were not significantly different between the 2 groups. Using the sliding dichotomy approach, there was no difference in the odds for unfavorable functional outcomes at 6 months (OR = 1.2, 95% CI 0.4-3.7). In this case-control study, the use of ACAP did not have a significant effect on mortality and adverse outcomes in patients with severe TBI. This would suggest that in severe TBI, ACAP use may not contribute significantly to the overall prognosis.


Assuntos
Anticoagulantes/efeitos adversos , Lesões Encefálicas Traumáticas/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Recuperação de Função Fisiológica/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Singapura
6.
Braz J Med Biol Res ; 52(9): e8290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482998

RESUMO

Tendon rupture is a very frequent accident involving average people and high-performance athletes. Clinical studies describe tendon recovery as a painful and slow process involving different biochemical and histological events. Ascorbic acid (AA) is a potent antioxidant as well as an important cofactor for collagen synthesis. In the current study, we evaluated if local treatment with AA is able to promote tendon repair in tenotomized rats. Animals were submitted to Achilles tendon rupture followed by surgical suture. Control and AA groups received in loco injection of saline solution (0.9% NaCl) and 30 mM AA, respectively. Histological and functional recovery of Achilles tendon tissue was evaluated at 7, 14, and 21 days post-surgery. Hematoxylin/eosin staining and collagen fluorescence analysis showed intense disarrangement of tendon tissue in the saline group. Tenotomized animals also showed hypercellularity in tendon tissue compared with non-tenotomized animals. The Achilles functional index (AFI) showed a significant decrease of tendon functionality in tenotomized animals at 7, 14, and 21 days post-surgery. AA accelerated tissue organization and the recovery of function of the Achilles tendons. The beneficial effect of AA treatment was also observed in the organization of the collagen network. Data presented in the current work showed that in loco treatment with AA accelerated the recovery of injured Achilles tendon post-surgery.


Assuntos
Tendão do Calcâneo/efeitos dos fármacos , Ácido Ascórbico/administração & dosagem , Colágeno/efeitos dos fármacos , Traumatismos dos Tendões/cirurgia , Tendão do Calcâneo/lesões , Tendão do Calcâneo/patologia , Animais , Colágeno/fisiologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/efeitos dos fármacos , Tenotomia , Cicatrização/efeitos dos fármacos
7.
Life Sci ; 235: 116844, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31499069

RESUMO

AIMS: 10-O-(N,N-dimethylaminoethyl)-ginkgolide B methanesulfonate (XQ-1H), a new derivative of ginkgolide B, has drawn great attention for its potent bioactivities against ischemia-induced injury. The purpose of this study was to further investigate the effect of XQ-1H against acute ischemic stroke by inducing middle cerebral artery occlusion/reperfusion (MCAO/R) injuries in mice. MAIN METHODS: Treatment of XQ-1H (78 or 39 mg/kg, i.g., bid) 2 h after MCAO improved motor skills and ameliorated the severity of brain infarction and apoptosis seen in the mice by diminishing pathological changes and the activation of a pro-apoptotic protein Cleaved-Caspase-3, which in turn induced anti-apoptotic Bcl-xL. Through introducing Wnt/ß-catenin signaling inhibitor XAV-939, XQ-1H was proven to intensively promoted neurogenesis in the peri-infarct cortex, subventricular area (SVZ) and the dentate gyrus (DG) subgranular area (SGZ) in a Wnt signal dependent way by compromising the activation of GSK3ß, which in turn upregulated Wnt1, ß-catenin, Neuro D1 and Cyclin D1, most possibly through the activation of PI3K/Akt signaling via the upregulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). KEY FINDINGS: We conclude that XQ-1H preserved the motor functions, limited apoptosis, and concomitantly promoted neurogenesis-related protein expression by Wnt signaling-dependently compromising GSK3ß/Caspase-3 activity and enhancing the expression of Wnt1/ß-catenin/Neuro D1/Cyclin D1 and Bcl-xL. SIGNIFICANCE: This research may benefit the development of stroke therapeutics targeting neurogenesis through Wnt upregulation by XQ-1H.


Assuntos
Apoptose/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Ginkgolídeos/farmacologia , Ginkgolídeos/uso terapêutico , Lactonas/farmacologia , Lactonas/uso terapêutico , Neurogênese/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Caspase 3/metabolismo , Ciclina D1/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Compostos Heterocíclicos com 3 Anéis/farmacologia , Infarto da Artéria Cerebral Média , Masculino , Camundongos , Fator de Crescimento Neural/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologia , Regulação para Cima/efeitos dos fármacos , Proteína bcl-X/metabolismo
8.
Exp Neurol ; 322: 113064, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31525347

RESUMO

In addition to local spinal cord dysfunction, spinal cord injury (SCI) can result in decreased skeletal muscle mitochondrial activity and muscle atrophy. Treatment with the FDA-approved ß2-adrenergic receptor (ADRB2) agonist formoterol has been shown to induce mitochondrial biogenesis (MB) in both the spinal cord and skeletal muscle and, therefore, has the potential to address comprehensive mitochondrial and organ dysfunction following SCI. Female C57BL/6 mice were subjected to moderate contusion SCI (80 Kdyn) followed by daily administration of vehicle or formoterol beginning 8 h after injury, a clinically relevant time-point characterized by a 50% decrease in mtDNA content in the injury site. As measured by the Basso Mouse Scale, formoterol treatment improved locomotor recovery in SCI mice compared to vehicle treatment by 7 DPI, with continued recovery observed through 21 DPI (3.5 v. 2). SCI resulted in 15% body weight loss in all mice by 3 DPI. Mice treated with formoterol returned to pre-surgery weight by 13 DPI, while no weight gain occurred in vehicle-treated SCI mice. Remarkably, formoterol-treated mice exhibited a 30% increase in skeletal muscle mass compared to those treated with vehicle 21 DPI (0.93 v. 0.72% BW), corresponding with increased MB and decreased skeletal muscle atrophy. These effects were not observed in ADRB2 knockout mice subjected to SCI, indicating that formoterol is acting via the ADRB2 receptor. Furthermore, knockout mice exhibited decreased basal spinal cord and skeletal muscle PGC-1α expression, suggesting that ADRB2 may play a role in mitochondrial homeostasis under physiological conditions. These data provide evidence for systemic ADRB2-mediated MB as a therapeutic avenue for the treatment of SCI.


Assuntos
Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Fumarato de Formoterol/farmacologia , Mitocôndrias/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/metabolismo , Atrofia Muscular/etiologia , Biogênese de Organelas , Receptores Adrenérgicos beta 2 , Traumatismos da Medula Espinal/complicações
9.
Muscle Nerve ; 60(5): 629-636, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31397919

RESUMO

INTRODUCTION: Neuroenhancing therapies are desired because repair of nerve injuries can fail to achieve recovery. We compared two neuroenhancing therapies, electrical stimulation (ES) and systemic tacrolimus (FK506), for their capabilities to enhance regeneration in the context of a rat model. METHODS: Rats were randomized to four groups: ES 0.5 mA, ES 2.0 mA, FK506, and repair alone. All groups underwent tibial nerve transection and repair, and outcomes were assessed by using twice per week walking track analysis, cold allodynia response, relative muscle mass, and nerve histology. RESULTS: Electrical stimulation and FK506 groups demonstrated improved functional recovery and myelinated axon counts distal to the repair compared with repair alone. Electrical stimulation provided improvements in nerve regeneration that were not different from optimized FK506 systemic administration. DISCUSSION: Providing ES after nerve repair improved regeneration and recovery in rats, with minimal differences in therapeutic efficacy to FK506, further demonstrating its clinical potential to improve management of nerve injuries.


Assuntos
Estimulação Elétrica/métodos , Imunossupressores/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Tacrolimo/farmacologia , Nervo Tibial/lesões , Animais , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/inervação , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Regeneração Nervosa/fisiologia , Procedimentos Neurocirúrgicos , Traumatismos dos Nervos Periféricos , Ratos , Recuperação de Função Fisiológica/fisiologia , Nervo Tibial/patologia , Nervo Tibial/cirurgia
10.
J Clin Neurosci ; 70: 92-95, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31439485

RESUMO

INTRODUCTION: Thrombolysis may affect ischemic stroke-related size, pattern and nature of infarcts, and has the potential to change aphasia presentation and recovery. Data on evolution of post-stroke aphasia following thrombolysis are still scarce. The aim of this study was to determine the course of language recovery through a well-validated language assessment battery after acute ischemic stroke and investigate whether traditional categorical classifications of aphasia can describe the clinical picture in post-thrombolysis phase. MATERIALS AND METHODS: Demographic, clinical, and language assessment data of 116 patients presenting sub-acute ischemic stroke aphasia (41 treated with r-tPA; 75 non-treated) were retrospectively analyzed. The participants were assessed by a clinical neuropsychologist with a variety of subtests taken from a well-validated Italian language battery (Neuro-Psychological Aphasia Evaluation). RESULTS: The percentage of resolved aphasia was significantly higher in treated patients compared to non-treated patients (p = 0.005) and global aphasia was more common in the non-treated group (non-treated 30.7% vs treated 17.1%). Aphasia subtypes and stroke etiologies showed no significant association, except for small vessel etiology and resolved aphasia (p = 0.041). Reperfusion treatment, baseline NIHSS, and lacunar stroke were the predictors of aphasia recovery. CONCLUSION: The percentage of resolved aphasia was significantly higher in the treated patients compared to the non-treated, with the latter showing a higher percentage of global aphasia. Identifying classic aphasia subtypes after thrombolysis is still possible since reperfused areas do not necessary change the classification or lead to completely different aphasic syndromes. Reperfusion treatment, baseline NIHSS, and lacunar stroke were the main predictors of aphasia recovery.


Assuntos
Afasia/etiologia , Fibrinolíticos/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Adulto , Idoso , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Feminino , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Terapia Trombolítica/métodos
11.
Clinics (Sao Paulo) ; 74: e674, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31433044

RESUMO

OBJECTIVE: To evaluate the effects of interleukin-6 (IL-6) and erythropoietin (EPO) in experimental acute spinal cord injury (SCI) in rats. METHODS: Using standardized equipment, namely, a New York University (NYU) Impactor, a SCI was produced in 50 Wistar rats using a 10-g weight drop from a 12.5-mm height. The rats were divided into the following 5 groups of 10 animals each: "Group EPO", treated with erythropoietin only; "Group EPO + IL-6", treated with both substances; "Group IL-6", receiving IL-6 administration only; "Group Placebo", receiving a placebo solution; and "Group Sham", submitted to an incomplete procedure (only laminectomy, without SCI). All drugs and the placebo solution were administered intraperitoneally for three weeks. The animals were followed up for 42 days. Functional motor recovery was monitored by the Basso, Beattie, and Bresnahan (BBB) scale on days 2, 7, 14, 21, 28, 35 and 42. Motor-evoked potential tests were performed on the 42nd day. Histological analysis was performed after euthanasia. RESULTS: The group receiving EPO exhibited superior functional motor results on the BBB scale. IL-6 administration alone was not superior to the placebo treatment, and the IL-6 combination with EPO yielded worse results than did EPO alone. CONCLUSIONS: Using EPO after acute SCI in rats yielded benefits in functional recovery. The combination of EPO and IL-6 showed benefits, but with inferior results compared to those of isolated EPO; moreover, isolated use of IL-6 resulted in no benefit.


Assuntos
Eritropoetina/uso terapêutico , Potencial Evocado Motor/efeitos dos fármacos , Interleucina-6/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Modelos Animais de Doenças , Eritropoetina/farmacologia , Interleucina-6/farmacologia , Masculino , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/patologia
12.
Biomed Res Int ; 2019: 9628065, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467921

RESUMO

The reparative process following spinal cord injury (SCI) is extremely complicated. Cells in the microenvironment express multiple inhibitory factors that affect axonal regeneration over a prolonged period of time. The axon growth inhibitory factor glycogen synthase kinase-3 (GSK-3) is an important factor during these processes. TDZD-8 (4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione) is the most effective and specific non-ATP-competitive inhibitor of GSK-3. Here, we show that administering TDZD-8 after SCI was associated with significantly inhibited neuronal apoptosis, upregulated GAP-43 expression, increased density of cortical spinal tract fibers around areas of injury, and increased Basso, Beattie, and Bresnahan (BBB) scores in the lower limbs. These findings support the notion that GSK-3 inhibitors promote neuronal cell regeneration and lower limb functional recovery.


Assuntos
Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Regeneração Nervosa/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Tiadiazóis/farmacologia , Animais , Apoptose/efeitos dos fármacos , Axônios/efeitos dos fármacos , Modelos Animais de Doenças , Proteína GAP-43/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/genética , Humanos , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Recuperação de Função Fisiológica/efeitos dos fármacos , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/fisiopatologia
13.
Neurology ; 93(9): e841-e850, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31358617

RESUMO

OBJECTIVE: Due to the continuing debates on the utility of high-dose methylprednisolone (MP) early after acute spinal cord injury (ASCI), we aimed to evaluate the therapeutic and adverse effects of high-dose MP according to the second National Acute Spinal Cord Injury Study (NASCIS-2) dosing protocol in comparison to no steroids in patients with ASCI by performing a meta-analysis on the basis of the current available clinical trials. METHODS: We searched PubMed and Cochrane Library (to May 22, 2018) for studies comparing neurologic recoveries, adverse events, and in-hospital costs between ASCI patients who underwent high-dose MP treatment or not. Data were synthesized with corresponding statistical models according to the degree of heterogeneity. RESULTS: We enrolled 16 studies (1,863 participants) including 3 randomized controlled trials (RCTs) and 13 observational studies. Pooled results indicated that MP was not associated with an increase in motor score improvement (RCTs: p = 0.84; observational studies: p = 0.44) and incidence of recovery by at least one grade on the American Spinal Injury Association Impairment Scale or Frankel (p = 0.53). Meanwhile, MP did not lead to better sensory recovery (p = 0.07). However, MP was associated with a significantly higher incidence of gastrointestinal hemorrhage (p = 0.04) and respiratory tract infection (p = 0.01). The difference in the overall in-hospital costs between MP and control groups was not statistically significant (p = 0.78). CONCLUSIONS: Based on the current evidence, high-dose MP treatment, in comparison to controls, does not contribute to better neurologic recoveries but may increase the risk of adverse events in patients with ASCI. Therefore, we recommend against routine use of high-dose MP early after ASCI.


Assuntos
Metilprednisolona/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Adolescente , Adulto , Ensaios Clínicos como Assunto/estatística & dados numéricos , Feminino , Humanos , Masculino , Metilprednisolona/efeitos adversos , Metilprednisolona/economia , Pessoa de Meia-Idade , Fármacos Neuroprotetores/efeitos adversos , Fármacos Neuroprotetores/economia , Fármacos Neuroprotetores/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Adulto Jovem
14.
J Orthop Surg Res ; 14(1): 199, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266512

RESUMO

BACKGROUND: We focused on the therapeutic effects of the stable gastric pentadecapeptide BPC 157 in spinal cord injury using a rat model. BPC 157, of which the LD1 has not been achieved, has been implemented as an anti-ulcer peptide in inflammatory bowel disease trials and recently in a multiple sclerosis trial. In animals, BPC 157 has an anti-inflammatory effect and therapeutic effects in functional recovery and the rescue of somatosensory neurons in the sciatic nerve after transection, upon brain injury after concussive trauma, and in severe encephalopathies. Additionally, BPC 157 affects various molecular pathways. METHODS: Therefore, BPC 157 therapy was administered by a one-time intraperitoneal injection (BPC 157 (200 or 2 µg/kg) or 0.9% NaCl (5 ml/kg)) 10 min after injury. The injury procedure involved laminectomy (level L2-L3) and a 60-s compression (neurosurgical piston (60-66 g) of the exposed dural sac of the sacrocaudal spinal cord). Assessments were performed at 1, 4, 7, 15, 30, 90, 180, and 360 days after injury. RESULTS: All of the injured rats that received BPC 157 exhibited consistent clinical improvement, increasingly better motor function of the tail, no autotomy, and resolved spasticity by day 15. BPC 157 application largely counteracted changes at the microscopic level, including the formation of vacuoles and the loss of axons in the white matter, the formation of edema and the loss of motoneurons in the gray matter, and a decreased number of large myelinated axons in the rat caudal nerve from day 7. EMG recordings showed a markedly lower motor unit potential in the tail muscle. CONCLUSION: Axonal and neuronal necrosis, demyelination, and cyst formation were counteracted. The functional rescue provided by BPC 157 after spinal cord injury implies that BPC 157 therapy can impact all stages of the secondary injury phase.


Assuntos
Fragmentos de Peptídeos/administração & dosagem , Proteínas/administração & dosagem , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Eletromiografia/métodos , Humanos , Vértebras Lombares , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/patologia , Cicatrização/fisiologia
15.
J Neuroinflammation ; 16(1): 141, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288834

RESUMO

BACKGROUND: Spinal cord injury (SCI) is a condition with few effective treatment options. The blood-spinal cord barrier consists of pericytes, astrocytes, and endothelial cells, which are collectively termed the neurovascular unit. These cells support spinal cord homeostasis by expressing tight junction proteins. Physical trauma to the spinal cord disrupts the barrier, which leads to neuroinflammation by facilitating immune cell migration to the damaged site in a process involving immune cell adhesion. Immunosuppressive strategies, including methylprednisolone (MPSS), have been investigated to treat SCI. However, despite some success, MPSS has the potential to increase a patient's susceptibility to wound infection and impaired wound healing. Hence, immunomodulation may be a more attractive approach than immunosuppression. Approved for modulating neuroinflammation in certain disorders, including Guillain-Barre syndrome, intravenous administration of human immunoglobulin G (hIgG) has shown promise in the setting of experimental SCI, though the optimal dose and mechanism of action remain undetermined. METHODS: Female adult Wistar rats were subjected to moderate-severe clip compression injury (35 g) at the C7-T1 level and randomized to receive a single intravenous (IV) bolus of hIgG (0.02, 0.2, 0.4, 1, 2 g/kg), MPSS (0.03 g/kg), or control buffer at 15 min post-SCI. At 24 h and 6 weeks post-SCI, molecular, histological, and neurobehavioral effects of hIgG were analyzed. RESULTS: At 24 h post-injury, human immunoglobulin G co-localized with spinal cord pericytes, astrocytes, and vessels. hIgG (2 g/kg) protected the spinal cord neurovasculature after SCI by increasing tight junction protein expression and reducing inflammatory enzyme expression. Improvements in vascular integrity were associated with changes in spinal cord inflammation. Interestingly, hIgG (2 g/kg) increased serum expression of inflammatory cytokines and co-localized (without decreasing protein expression) with spinal cord vascular cell adhesion molecule-1, a protein used by immune cells to enter into inflamed tissue. Acute molecular benefits of hIgG (2 g/kg) led to greater tissue preservation, functional blood flow, and neurobehavioral recovery at 6 weeks post-SCI. Importantly, the effects of hIgG (2 g/kg) were superior to control buffer and hIgG (0.4 g/kg), and comparable with MPSS (0.03 g/kg). CONCLUSIONS: hIgG (2 g/kg) is a promising therapeutic approach to mitigate secondary pathology in SCI through antagonizing immune cell infiltration at the level of the neurovascular unit.


Assuntos
Imunoglobulinas Intravenosas/farmacologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/patologia , Junções Íntimas/efeitos dos fármacos , Animais , Medula Cervical/irrigação sanguínea , Medula Cervical/efeitos dos fármacos , Medula Cervical/patologia , Células Endoteliais/efeitos dos fármacos , Feminino , Humanos , Distribuição Aleatória , Ratos , Ratos Wistar
16.
Eur J Med Res ; 24(1): 27, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351486

RESUMO

PURPOSE: To summarize the techniques and clinical effectiveness in treating scaphoid nonunion with nickel-titanium (Ni-Ti) arched shape-memory alloy connector in combination with autologous iliac bone grafts. METHODS: This study retrospectively analyzed 18 scaphoid nonunion cases treated with arched connectors with autologous iliac bone grafts. Based on scaphoid nonunion, 2 cases were classified as type II (fibrous union), 4 cases as type III (mild sclerotic union), 6 cases as type IV (moderate resorption and sclerosis), 5 cases as type V (severe bone resorption and sclerosis), and 1 case as type VI (pseudarthrosis formation). At the first 4, 8 and 12 weeks after the surgery, wrist anteroposterior, lateral X-ray were obtained, respectively, to evaluate bone healing. Patients who had not yet reached the standard of healing at 12 weeks after surgery would continue to receive additional appointments for follow-up visits, such as 14 weeks, 16 weeks, 18 weeks after surgery, until their imaging studies had achieved satisfactory bone healing. Clinical effectiveness was evaluated comprehensively, based on bone union time, Mayo wrist score, and visual analog pain score. RESULTS: All 18 patients achieved satisfactory reduction and fixation with a mean union time of 4.2 months. Preoperative Mayo wrist score averaged 57.4 and average final postoperative follow-up was 91.4. On the other hand, mean preoperative VAS score was 6.8, and final postoperative follow-up average was 1.6. Mayo wrist score of the overall treatment effectiveness was excellent (90-100) in 12 cases, good (80-90) in 5 cases, and acceptable (60-80) in 1 case with zero poor (below 60) cases observed. Statistical analysis suggested that a statistically significant improvement in fracture healing, wrist function recovery and visual analog pain after surgery when compared to the scores of the patients before surgery. CONCLUSION: Using Ni-Ti arched shape-memory alloy connector in combination with autologous bone grafting provided a new modality to treat scaphoid nonunions in a less traumatic, convenient to operate and satisfactory manner in treatment outcomes, and thus is worthy of further application.


Assuntos
Transplante Ósseo , Fraturas não Consolidadas/cirurgia , Níquel/farmacologia , Osso Escafoide/cirurgia , Titânio/farmacologia , Adulto , Fraturas não Consolidadas/fisiopatologia , Humanos , Masculino , Recuperação de Função Fisiológica/efeitos dos fármacos , Osso Escafoide/diagnóstico por imagem , Osso Escafoide/fisiopatologia , Resultado do Tratamento , Punho/fisiopatologia
17.
J Neuroinflammation ; 16(1): 160, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358003

RESUMO

BACKGROUND: Spinal cord injury (SCI) is a catastrophic trauma accompanied by intralesional bleeding and neuroinflammation. Recently, there is increasing interest in tranexamic acid (TXA), an anti-fibrinolytic drug, which can reduce the bleeding volume after physical trauma. However, the efficacy of TXA on the pathology of SCI remains unknown. METHODS: After producing a contusion SCI at the thoracic level of mice, TXA was intraperitoneally administered and the bleeding volume in the lesion area was quantified. Tissue damage was evaluated by immunohistochemical and gene expression analyses. Since heme is one of the degraded products of red blood cells (RBCs) and damage-associated molecular pattern molecules (DAMPs), we examined the influence of heme on the pathology of SCI. Functional recovery was assessed using the open field motor score, a foot print analysis, a grid walk test, and a novel kinematic analysis system. Statistical analyses were performed using Wilcoxon's rank-sum test, Dunnett's test, and an ANOVA with the Tukey-Kramer post-hoc test. RESULTS: After SCI, the intralesional bleeding volume was correlated with the heme content and the demyelinated area at the lesion site, which were significantly reduced by the administration of TXA. In the injured spinal cord, toll-like receptor 4 (TLR4), which is a DAMP receptor, was predominantly expressed in microglial cells. Heme stimulation increased TLR4 and tumor necrosis factor (TNF) expression levels in primary microglial cells in a dose-dependent manner. Similarly to the in vitro experiments, the injection of non-lysed RBCs had little pathological influence on the spinal cord, whereas the injection of lysed RBCs or heme solution significantly upregulated the TLR4 and TNF expression in microglial cells. In TXA-treated SCI mice, the decreased expressions of TLR4 and TNF were observed at the lesion sites, accompanied by a significant reduction in the number of apoptotic cells and better functional recovery in comparison to saline-treated control mice. CONCLUSION: The administration of TXA ameliorated the intralesional cytotoxicity both by reducing the intralesional bleeding volume and preventing heme induction of the TLR4/TNF axis in the SCI lesion. Our findings suggest that TXA treatment may be a therapeutic option for acute-phase SCI.


Assuntos
Heme/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Receptor 4 Toll-Like/metabolismo , Ácido Tranexâmico/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Animais , Feminino , Camundongos , Atividade Motora/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Traumatismos da Medula Espinal/metabolismo , Vértebras Torácicas , Ácido Tranexâmico/farmacologia
18.
Neurochem Res ; 44(8): 2007-2019, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31325156

RESUMO

Spinal cord injury (SCI) leads to neuronal death resulting in central nervous system (CNS) dysfunction; however, the pathogenesis is still poorly understood. Melatonin (MT), a hormone secreted mainly by the pineal gland, is associated with neuroprotective effects against SCI. Enhanced autophagy can promote the recovery of locomotor function and reduce apoptosis after SCI. Interestingly, MT increases autophagy in SCI in vivo. Nevertheless, the ability of MT to increase autophagy and decrease apoptosis, and the potential effects on the recovery of motor neurons in the anterior horn after SCI remain to be clarified. In this study, we discovered that MT treatment improved motor function recovery in a rat SCI model. Indeed, MT upregulated the expression of the phosphatidylinositol 3-kinase (PI3K), while expression of protein kinase B (AKT) and mammalian target of rapamycin (mTOR) was downregulated after SCI. Additionally, MT increased the expression of autophagy-activating proteins, while the expression of apoptosis-activating proteins in neurons was decreased following SCI. Furthermore, autophagy was inhibited, while apoptosis was induced in SCI model rats and lipopolysaccharide (LPS)-stimulated primary neurons by treatment with MT, the PI3K inhibitor 3-methyladenine (3-MA) and mTOR inhibitor Rapamycin (Rapa). Collectively, our results suggest that MT can improve the recovery of locomotor function by enhancing autophagy as well as reducing apoptosis after SCI in rats, probably via the PI3K/AKT/mTOR signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Melatonina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Locomoção/efeitos dos fármacos , Masculino , Neurônios/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Serina-Treonina Quinases TOR/metabolismo
19.
Nutrients ; 11(7)2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31337122

RESUMO

Tart cherry juice (TC) and pomegranate juice (POM) have been demonstrated to reduce symptoms of exercise-induced muscle damage (EIMD), but their effectiveness has not been compared. This randomized, double-blind, parallel study compared the effects of TC and POM on markers of EIMD. Thirty-six non-resistance trained men (age 24.0 (Interquartile Range (IQR) 22.0, 33.0) years, body mass index (BMI) 25.6 ± 4.0 kg·m-2) were randomly allocated to consume 2 × 250 mL of: TC, POM, or an energy-matched fruit-flavored placebo drink twice daily for nine days. On day 5, participants undertook eccentric exercise of the elbow flexors of their non-dominant arm. Pre-exercise, immediately post-exercise, and at 24 h, 48 h, 72 h and 96 h post-exercise, maximal isometric voluntary contraction (MIVC), delayed onset muscle soreness (DOMS), creatine kinase (CK), and range of motion (ROM) were measured. The exercise protocol induced significant decreases in MIVC (p < 0.001; max decrease of 26.8%, 24 h post-exercise) and ROM (p = 0.001; max decrease of 6.8%, 72 h post-exercise) and significant increases in CK (p = 0.03; max increase 1385 U·L-1, 96 h post-exercise) and DOMS (p < 0.001; max increase of 26.9 mm, 48 h post-exercise). However, there were no statistically significant differences between treatment groups (main effect of group p > 0.05 or group x time interaction p > 0.05). These data suggest that in non-resistance trained men, neither TC nor POM enhance recovery from high-force eccentric exercise of the elbow flexors.


Assuntos
Exercício Físico/fisiologia , Sucos de Frutas e Vegetais , Músculo Esquelético/efeitos dos fármacos , Prunus avium , Adulto , Método Duplo-Cego , Humanos , Masculino , Mialgia , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Treinamento de Resistência/efeitos adversos , Adulto Jovem
20.
J Neuroinflammation ; 16(1): 124, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31186006

RESUMO

BACKGROUND: Spinal cord injury (SCI) usually causes a devastating lifelong disability for patients. After a traumatic lesion, disruption of the blood-spinal cord barrier induces the infiltration of macrophages into the lesion site and the activation of resident glial cells, which release cytokines and chemokines. These events result in a persistent inflammation, which has both detrimental and beneficial effects, but eventually limits functional recovery and contributes to the appearance of neuropathic pain. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that regulate the expression of inflammatory genes by interacting with acetylated lysine residues. While BET inhibitors are a promising therapeutic strategy for cancer, little is known about their implication after SCI. Thus, the current study was aimed to investigate the anti-inflammatory role of BET inhibitors in this pathologic condition. METHODS: We evaluated the effectiveness of the BET inhibitor JQ1 to modify macrophage reactivity in vitro and to modulate inflammation in a SCI mice model. We analyzed the effects of BET inhibition in pro-inflammatory and anti-inflammatory cytokine production in vitro and in vivo. We determined the effectiveness of BET inhibition in tissue sparing, inflammation, neuronal protection, and behavioral outcome after SCI. RESULTS: We have found that the BET inhibitor JQ1 reduced the levels of pro-inflammatory mediators and increased the expression of anti-inflammatory cytokines. A prolonged treatment with JQ1 also decreased reactivity of microglia/macrophages, enhanced neuroprotection and functional recovery, and acutely reduced neuropathic pain after SCI. CONCLUSIONS: BET protein inhibition is an effective treatment to regulate cytokine production and promote neuroprotection after SCI. These novel results demonstrate for the first time that targeting BET proteins is an encouraging approach for SCI repair and a potential strategy to treat other inflammatory pathologies.


Assuntos
Azepinas/farmacologia , Citocinas/efeitos dos fármacos , Proteínas do Tecido Nervoso/antagonistas & inibidores , Fármacos Neuroprotetores/farmacologia , Receptores de Superfície Celular/antagonistas & inibidores , Traumatismos da Medula Espinal/metabolismo , Triazóis/farmacologia , Animais , Citocinas/biossíntese , Feminino , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Recuperação de Função Fisiológica/efeitos dos fármacos
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