RESUMO
The aim of this study was to investigate whether exogenous retinoic acid (RA) can upregulate the mRNA and protein expression of growth-associated protein 43 (GAP-43), thereby promoting brain functional recovery in a rat distal middle cerebral artery occlusion (MCAO) model of ischemia. A total of 216 male Sprague Dawley rats weighing 300-320 g were divided into 3 groups: sham-operated group, MCAO+vehicle group and MCAO+RA group. Focal cortical infarction was induced with a distal MCAO model. The expression of GAP-43 mRNA and protein in the ipsilateral perifocal region was assessed using qPCR and immunocytochemistry at 1, 3, 7, 14, 21, and 28 days after distal MCAO. In addition, an intraperitoneal injection of RA was given 12 h before MCAO and continued every day until the animal was sacrificed. Following ischemia, the expression of GAP-43 first increased considerably and then decreased. Administration of RA reduced infarction volume, promoted neurological functional recovery and upregulated expression of GAP-43. Administration of RA can ameliorate neuronal damage and promote nerve regeneration by upregulating the expression of GAP-43 in the perifocal region after distal MCAO.
Assuntos
Proteína GAP-43/metabolismo , Expressão Gênica/efeitos dos fármacos , Infarto da Artéria Cerebral Média/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Tretinoína/farmacologia , Regulação para Cima/efeitos dos fármacos , Animais , Isquemia Encefálica/prevenção & controle , Proteína GAP-43/genética , Imuno-Histoquímica , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Masculino , Distribuição Aleatória , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
The aim of this study was to investigate whether exogenous retinoic acid (RA) can upregulate the mRNA and protein expression of growth-associated protein 43 (GAP-43), thereby promoting brain functional recovery in a rat distal middle cerebral artery occlusion (MCAO) model of ischemia. A total of 216 male Sprague Dawley rats weighing 300–320 g were divided into 3 groups: sham-operated group, MCAO+vehicle group and MCAO+RA group. Focal cortical infarction was induced with a distal MCAO model. The expression of GAP-43 mRNA and protein in the ipsilateral perifocal region was assessed using qPCR and immunocytochemistry at 1, 3, 7, 14, 21, and 28 days after distal MCAO. In addition, an intraperitoneal injection of RA was given 12 h before MCAO and continued every day until the animal was sacrificed. Following ischemia, the expression of GAP-43 first increased considerably and then decreased. Administration of RA reduced infarction volume, promoted neurological functional recovery and upregulated expression of GAP-43. Administration of RA can ameliorate neuronal damage and promote nerve regeneration by upregulating the expression of GAP-43 in the perifocal region after distal MCAO.
Assuntos
Animais , Masculino , Proteína GAP-43/metabolismo , Expressão Gênica/efeitos dos fármacos , Infarto da Artéria Cerebral Média/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Tretinoína/farmacologia , Regulação para Cima/efeitos dos fármacos , Isquemia Encefálica/prevenção & controle , Proteína GAP-43/genética , Imuno-Histoquímica , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Distribuição Aleatória , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
De forma compactada se explica la relación biológicamente plausible que existe entre la aparición de accidentes cerebrovasculares, particularmente de infarto cerebral isquémico aterotrombótico y la precedencia de enfermedad periodontal inmuno-inflamatoria crónica. Se sugiere la necesidad de estudios que vinculen ambas entidades para conciliar los resultados de las investigaciones internacionales con las realizadas en nuestro medio. Se propone el análisis del estado periodontal en los pacientes pertenecientes a grupos de riesgo o víctimas de enfermedades cerebrovasculares. La consideración de la enfermedad periodontal inmuno-inflamatoria crónica como un factor de riesgo más para el infarto cerebral isquémico aterotrombótico, debe pasar de una interrogante a una estrategia(AU)
The biologically plausible relation existing between the occurrence of cerebrovascular accidents, particularly of atherothrombotic ischemic stroke, and the presence of chronic immunoinflammatory periodontal disease is explained in a compacted way. The need for studies linking both entities is suggested for conciliating the results of the international researches with those carried out in our environment. The analysis of the periodontal state in patients from risk groups of victims on cerebrovascular disease is proposed. Considering the chronic immunoinflammatory periodontal disease as a risk factor for atherothrombotic ischemic stroke should pass from a question to a strategy(AU)
Assuntos
Humanos , Infarto da Artéria Cerebral Média/etiologia , Infarto da Artéria Cerebral Média/prevenção & controle , Doenças Periodontais/complicações , Fatores de RiscoRESUMO
The aim of this study was to investigate the influence of atorvastatin on the opening of the mitochondrial permeability transition pore (MPTP) and the expression of cytochrome C (Cyt C) in Sprague-Dawley rats with cerebral ischemia-reperfusion (I/R). The rat model of cerebral artery ischemia was established by the suture-occluded method with ischemia for 2 h and reperfusion for 72 h. Thirty-four male rats were randomly divided into four groups: the normal group and the sham-operation group without any treatment, the I/R group with only intragastric administration of normal saline, and the intervention group, which received intragastric administration of 10 mg/kg atorvastatin at different times. All rats were sacrificed at 72 h. Compared with the I/R group, the morphology of nerve cells in the intervention group was reduced, the number of TUNEL-positive cells decreased, the expression of cortical cytoplasm Cyt C decreased, and the mitochondrial absorbance value increased. All of these differences were statistically significant. Atorvastatin could inhibit neuronal apoptosis and alleviate the cerebral I/R injury. The mechanism may be related to the blocking of the MPTP opening and the subsequent reduction of Cyt C release.
Assuntos
Anticolesterolemiantes/farmacologia , Isquemia Encefálica/prevenção & controle , Ácidos Heptanoicos/farmacologia , Infarto da Artéria Cerebral Média/prevenção & controle , Proteínas de Transporte da Membrana Mitocondrial/efeitos dos fármacos , Pirróis/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Atorvastatina , Isquemia Encefálica/metabolismo , Citocromos c/metabolismo , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média/metabolismo , Masculino , Poro de Transição de Permeabilidade Mitocondrial , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismoRESUMO
We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.
Assuntos
Animais , Masculino , Teste de Esforço/métodos , Terapia por Exercício/métodos , Infarto da Artéria Cerebral Média/prevenção & controle , Esforço Físico , Condicionamento Físico Animal/instrumentação , Calibragem , Infarto Cerebral/patologia , Infarto Cerebral/prevenção & controle , Modelos Animais de Doenças , Desenho de Equipamento , Invenções , Infarto da Artéria Cerebral Média/patologia , Resistência Física , Distribuição Aleatória , Ratos Wistar , Índice de Gravidade de Doença , Software , Fatores de TempoRESUMO
We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.
Assuntos
Teste de Esforço/métodos , Terapia por Exercício/métodos , Infarto da Artéria Cerebral Média/prevenção & controle , Condicionamento Físico Animal/instrumentação , Esforço Físico , Animais , Calibragem , Infarto Cerebral/patologia , Infarto Cerebral/prevenção & controle , Modelos Animais de Doenças , Desenho de Equipamento , Infarto da Artéria Cerebral Média/patologia , Invenções , Masculino , Resistência Física , Distribuição Aleatória , Ratos Wistar , Índice de Gravidade de Doença , Software , Fatores de TempoRESUMO
There is much biochemical evidence, but very few studies in animal models of stroke in vivo, to suggest that Ginkgo biloba (EGb 761) may offer neuroprotection against regional, ischemic brain damage; additional investigations are needed to ensure future clinical trials. This study reports the effects of EGb 761 given acutely or chronically before ischemia. Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h and the brain infarct size was assessed 24 h later. Dipyrone (100 mg/kg, i.p.) was injected 30 min before ischemia, and 2.5 and 5.5 h after ischemia, to reduce ischemia-induced fever. EGb 761 (Tebonin) was given acutely (200 mg/kg, p.o., 60 min before ischemia) or chronically (100 mg/kg, p.o., once daily, for 14 days before ischemia). Acute or chronic treatment with EGb 761, either alone or in combination with dipyrone, did not reduce the infarct size compared with saline alone (p > 0.05). Dipyrone failed to prevent ischemia-induced fever during the intra-ischemic period (p > 0.05 vs saline; p < 0.001 vs sham). In the reperfusion phase, dipyrone reduced fever to normothermic levels in the group treated acutely with EGb 761 (p < 0.01 vs saline, p > 0.05 vs sham) but not after chronic EGb 761 (p < 0.01 vs sham), indicating possible pharmacokinetic interaction. In conclusion, within the context of unprevented, ischemia-induced fever, the present results demonstrate that EGb 761 has no significant effect on brain infarct size.