RESUMO
Recent studies showed that pathology of alcoholic encephalopathy was associated with cerebral vascular damage. TMP (tetramethyl- pyrazine) is widely used in the treatment of cerebrovascular diseases, however, it has not been reported whether TMP can relieve alcohol-induced cerebral vascular damages. The study was performed to investigate the learning and memory, cerebrovascular pathological changes and the expressions of vascular endothelial growth factor (VEGF) and serum levelsofendothelin-1 (ET-1) in the rat model of chronic alcoholic encephalopathy, and explore the effects of TMP intervention on alcoholic encephalopathy. In the present study, the rat model of chronic alcoholic encephalopathy was established by the gavage administration of alcohol; the learning and memory ability was tested by Morris water maze; the expression of VEGF was measured by RT-PCR and Western blot; and the serum levels of ET-1 was measured by radioimmunoassay. We found that alcohol intoxication impaired learning and memory, induced VEGF overexpression and increased ET 1 concentrations. TMP intervention improved learning abilities, increased the VEGF expression and reduced ET-1 level. These results indicate that TMP exhibits therapeutic effects on chronic alcoholic encephalopathy.
Assuntos
Transtornos do Sistema Nervoso Induzidos por Álcool/tratamento farmacológico , Circulação Cerebrovascular/efeitos dos fármacos , Pirazinas/uso terapêutico , Vasodilatadores/uso terapêutico , Transtornos do Sistema Nervoso Induzidos por Álcool/complicações , Transtornos do Sistema Nervoso Induzidos por Álcool/fisiopatologia , Animais , Modelos Animais de Doenças , Endotelina-1/sangue , Aprendizagem/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Pirazinas/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/análise , Vasodilatadores/farmacologiaRESUMO
Microglia function as the primary immune effector cells in the brain and play a pivotal role in the neuroinflammatory processes which are critical component of neurodegenerative diseases. Alcohol abuse has been considered as one of the common reasons for neurodegeneration although the causative factors are poorly understood. Here, we investigated whether activated microglia were implicated in neurodegeneration and cognitive dysfunctions in adult rats after intermittent alcohol abuse. Rats were given orally a priming dose of 5 g/kg ethanol and then 3g/kg every 8h for 4 days, followed by a 3-day ethanol-withdrawal period. These 4 days of ethanol treatments were repeated four times intermittently to simulate the binge drinking of human alcoholics. Neurodegeneration and microglial activation were detected by Fluoro-Jade B staining, Golgi staining, immunohistochemistry and ELISA, respectively, while cognitive function was assessed by Morris water maze and novel object recognition. The results showed that microglial activation and inflammatory cytokine expression were obvious in the parietal association cortex, entorhinal cortex and hippocampus accompanied by neurodegeneration following ethanol treatment. Moreover, learning and memory abilities also declined following ethanol treatments. However, the hypertrophied microglia disappeared accompanied by the decrease of inflammatory cytokines levels on day 4, and ramified microglial proliferated significantly on day 14 after ethanol withdrawal, along with a recovery from neuronal damage and cognitive impairment. Thus, the present study indicated that activated microglia might be involved in neurodegeneration and cognitive dysfunctions induced by intermittent ethanol exposure, and neurotrophic microglia appear to have a contribution to the recovery during abstinence.
