TGN-020 Alleviate Inflammation and Apoptosis After Cerebral Ischemia-Reperfusion Injury in Mice Through Glymphatic and ERK1/2 Signaling Pathway.

Post-stroke acute inhibition of aquaporin 4 (AQP4) is known to exacerbate inflammation and apoptosis, yet the underlying mechanisms are not fully understood. The objective of this study was to investigate the specific mechanism of inflammation and apoptosis following cerebral ischemia-reperfusion (I/R) injury using the AQP4-specific inhibitor, N-(1,3,4-thiadiazol-2-yl) pyridine-3-carboxamide dihydrochloride (TGN-020). Ischemic stroke was induced in mice using the middle cerebral artery occlusion (MCAO) model. The C57/BL6 mice were randomly divided into three groups as follows: sham operation, I/R 48 h, and TGN-020 + I/R 48 h treatment. All mice were subjected to a series of procedures. These procedures encompassed 2,3,5-triphenyltetrazolium chloride (TTC) staining, neurological scoring, fluorescence tracing, western blotting, immunofluorescence staining, and RNA sequencing (RNA-seq). The glymphatic function in the cortex surrounding cerebral infarction was determined using tracer, glial fibrillary acid protein (GFAP), AQP4 co-staining, and beta-amyloid precursor protein (APP) staining; differential genes were detected using RNA-seq. The influence of TGN-020 on the extracellular signal-regulated kinase 1/2 (ERK) 1/2 pathway was confirmed using the ERK1/2 pathway agonists Ro 67-7467. Additionally, we examined the expression of inflammation associated with microglia and astrocytes after TGN-020 and Ro 67-7467 treatment. Compared with I/R group, TGN-020 alleviated glymphatic dysfunction by inhibiting astrocyte proliferation and reducing tracer accumulation in the peri-infarct area. RNA-seq showed that the differentially expressed genes were mainly involved in the activation of astrocytes and microglia and in the ERK1/2 pathway. Western blot and immunofluorescence further verified the expression of associated inflammation. The inflammation and cell apoptosis induced by I/R are mitigated by TGN-020. This mitigation occurs through the improvement of glymphatic function and the inhibition of the ERK1/2 pathway.

Limb Remote Ischemic Postconditioning Improves Glymphatic Dysfunction After Cerebral Ischemia-Reperfusion Injury.

BACKGROUND: Delayed neuronal damage can be caused or aggravated after cerebral ischemia-reperfusion (I/R) injury. Recent studies have shown that glymphatic system dysfunction after cerebral ischemia-reperfusion injury is involved in ischemic brain edema and neuroinflammation, thereby regulating cerebral ischemia-reperfusion injury. The aim of this study is to investigate the changes of glymphatic system after cerebral ischemia-reperfusion injury and whether limb remote ischemic postconditioning (LRIP) can improve the function of glymphatic system to protect the brain. METHODS: To establish a focal brain I/R injury mouse model, this study utilized the middle cerebral artery occlusion/reperfusion (MCAO/R) method. The present study classified eight-week-old C57BL/6 male mice into three groups. The changes in glymphatic function in different periods of ischemia and reperfusion were analyzed through immunofluorescence, transmission electron microscopy (TEM), and Western-Blot (WB) assays. The contents of the evaluation included cerebrospinal fluid flow, swelling degree of brain tissue, aquaporin-4 (AQP4) expression and polarization, and amyloid-ß (Aß) excretion. RESULTS: In the early stages of cerebral ischemia, cerebrospinal fluid (CSF) flow is disturbed, accompanied by a decrease in AQP4 polarization. The polarity of AQP4 decreased from 12 h to 72 h of reperfusion, the Aß deposition. LRIP can increase the expression of ß-DG and AQP4 polarization, reduce the deposition of Aß, improve the function of the glymphatic system, and reduce the expression of AQP4 to play A protective role in brain. CONCLUSION: Glymphatic system impaired after cerebral ischemia-reperfusion injury in mice. LRIP may play a neuroprotective role by improving glymphatic function after I/R.

Application of functional training on physical fitness in basketball / Aplicação do treinamento funcional sobre a aptidão física no basquetebol / Aplicación del entrenamiento funcional en la aptitud física en el baloncesto

ABSTRACT Introduction: Basketball is a predominant competitive sport among the masses. Its practice requires scoring as many points as possible within a specific time limit, manifesting a short-duration, high-intensity intermittent training session. To meet the sport's requirements, the athlete must have ample directional control, rapid changes in speed, and good jumping ability. Objective: Verify the effects of functional training on basketball players aiming to improve explosive power, stability, and agility. Methods: 18 college basketball players were randomly selected as volunteers for the investigation. They were randomly divided into experimental and control groups. Only to the experimental one was functional physical training added during routine training. The trial lasted for eight weeks. All participants were tested for agility, strength, speed, endurance, power, and cartilage repair before and after the experiment. Finally, a comprehensive statistical data analysis was performed. Results: There were significant differences between the experimental group and the control group in push-ups, 3200-meter run, physical acuity detection, 17 sidelines, and running items, and touch height (P<0.05). In the experimental group, there was no significant difference in high school grades (P>0.05). There was significant statistical significance in the supine project, the 3200-meter athletics project, the 17 sideline projects, and the touchdown project (P<0.05). Conclusion: The physical fitness of the experimental group improved significantly after functional physical training. After routine physical training, the control group athletes had significantly positive absolute strength and endurance results. Overall, functional fitness training is superior to conventional fitness training. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O basquetebol é um esporte de competição predominante entre as massas. Sua prática requer o maior número possível de pontos dentro de um limite de tempo específico, manifestando uma sessão de treinamento intermitente de curta duração e de alta intensidade. Para atender aos requisitos esportivos, é necessário que o atleta tenha um amplo controle direcional, mudanças rápidas de velocidade e boa capacidade de salto. Objetivo: Verificar os efeitos do treinamento funcional em jogadores de basquetebol visando melhorar o poder explosivo, estabilidade e agilidade. Métodos: Foram selecionados aleatoriamente 18 jogadores universitários de basquetebol como voluntários para a investigação. Divididos aleatoriamente em grupos experimental e controle. Apenas ao experimental foi adicionado o treinamento físico funcional durante o treinamento de rotina. O ensaio durou oito semanas. Todos os participantes foram testados quanto a agilidade, força, velocidade, resistência, potência e reparo de cartilagem antes e depois do experimento. Finalmente, efetuou-se uma abrangente análise estatística de dados. Resultados: Verificou-se diferenças significativas entre o grupo experimental e o grupo de controle em flexões, 3200 metros de corrida, detecção de acuidade física, 17 itens de linha lateral e itens de corrida e altura de toque (P<0,05). No grupo experimental, não houve diferença significativa nas notas do ensino médio (P>0,05). Houve significância estatística significativa no projeto de supino, no projeto de atletismo de 3200 metros, nos 17 projetos de linha lateral, e no projeto de retoque (P<0,05). Conclusão: A aptidão física do grupo experimental melhorou significativamente após o treinamento físico funcional. Após o treinamento físico de rotina, os atletas do grupo de controle tiveram resultados significativamente positivos sobre força e resistência absolutas. Em geral, o treinamento de aptidão física funcional é superior ao treinamento de aptidão física convencional. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

Resumen Introducción: El baloncesto es un deporte de competición predominante entre las masas. Su práctica requiere el mayor número posible de puntos dentro de un límite de tiempo específico, manifestando una sesión de entrenamiento intermitente de corta duración y alta intensidad. Para cumplir con los requisitos deportivos, es necesario que el atleta tenga un amplio control direccional, rápidos cambios de velocidad y una buena capacidad de salto. Objetivo: Verificar los efectos del entrenamiento funcional en jugadores de baloncesto con el objetivo de mejorar la potencia explosiva, la estabilidad y la agilidad. Métodos: 18 jugadores de baloncesto universitario fueron seleccionados al azar como voluntarios para la investigación. Se dividieron aleatoriamente en grupos experimentales y de control. Sólo al experimental se le añadió el entrenamiento físico funcional durante el entrenamiento rutinario. La prueba duró ocho semanas. Todos los participantes fueron sometidos a pruebas de agilidad, fuerza, velocidad, resistencia, potencia y reparación del cartílago antes y después del experimento. Por último, se realizó un exhaustivo análisis estadístico de los datos. Resultados: Hubo diferencias significativas entre el grupo experimental y el grupo de control en las flexiones de brazos, la carrera de 3200 metros, la detección de la agudeza física, los 17 elementos de la banda y la carrera y la altura del toque (P<0,05). En el grupo experimental, no hubo diferencias significativas en las calificaciones de la escuela secundaria (P>0,05). Hubo una significación estadística significativa en el proyecto de decúbito supino, el proyecto de 3200 metros de atletismo, los 17 proyectos de banda y el proyecto de touchdown (P<0,05). Conclusión: La aptitud física del grupo experimental mejoró significativamente tras el entrenamiento físico funcional. Tras el entrenamiento físico rutinario, los atletas del grupo de control obtuvieron resultados significativamente positivos en cuanto a fuerza y resistencia absolutas. En general, el entrenamiento de aptitud física funcional es superior al entrenamiento de aptitud física convencional. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.