Neuroprotective effects of Aceglutamide on motor function in a rat model of cerebral ischemia and reperfusion.

Zhang, Rui; Yang, Nan; Ji, Chao; Zheng, Ji; Liang, Zhen; Hou, Chun-Ying; Liu, Yan-Yong; Zuo, Ping-Ping

Zhang, Rui; Yang, Nan; Ji, Chao; Zheng, Ji; Liang, Zhen; Hou, Chun-Ying; Liu, Yan-Yong; Zuo, Ping-Ping.

Restor Neurol Neurosci ; 33(5): 741-59, 2015.

Article en En | MEDLINE | ID: mdl-26444640

RESUMEN

PURPOSE: To investigate the effect and underlying mechanism of Aceglutamide on motor dysfunction in rats after cerebral ischemia-reperfusion. METHODS: Adult male Sprague-Dawley rats were subjected to 2 h transient middle cerebral artery occlusion (MCAO). Aceglutamide or vehicle was intraperitoneally given to rats at 24 h after reperfusion and lasted for 14 days. Subsequently functional recovery was assessed and number of tyrosine hydroxylase (TH)-positive neurons in substantia nigra (SN) was analyzed. Tumor necrosis factor receptor-associated factor 1(TRAF1), P-Akt and Bcl-2/Bax were determined in mesencephalic tissue by Western blot method. PC12 cells and primary cultured mesencephalic neurons were employed to further investigate the mechanism of Aceglutamide. RESULTS: Aceglutamide treatment improved behavioral functions, reduced the infarction volume, and elevated the number of TH-positive neurons in the SN. Moreover, Aceglutamide significantly attenuated neuronal apoptosis in the SN. Meanwhile Aceglutamide treatment significantly inhibited the expression of TRAF1 and up-regulated the expression of P-Akt and Bcl-2/Bax ratio both in vitro and in vivo. CONCLUSIONS: Aceglutamide ameliorated motor dysfunction and delayed neuronal death in the SN after ischemia, which involved the inhibition of pro-apoptotic factor TRAF1 and activation of Akt/Bcl-2 signaling pathway. These data provided experimental information for applying Aceglutamide to ischemic stroke treatment.

Asunto(s)

Isquemia Encefálica/tratamiento farmacológico; Glutamina/análogos & derivados; Trastornos del Movimiento/tratamiento farmacológico; Fármacos Neuroprotectores/farmacología; Animales; Isquemia Encefálica/patología; Muerte Celular/efectos de los fármacos; Muerte Celular/fisiología; Corteza Cerebral/efectos de los fármacos; Corteza Cerebral/metabolismo; Corteza Cerebral/patología; Modelos Animales de Enfermedad; Relación Dosis-Respuesta a Droga; Glutamina/química; Glutamina/farmacología; Infarto de la Arteria Cerebral Media; Inyecciones Intraperitoneales; Masculino; Mesencéfalo/efectos de los fármacos; Mesencéfalo/metabolismo; Mesencéfalo/patología; Trastornos del Movimiento/patología; Trastornos del Movimiento/fisiopatología; Neuronas/efectos de los fármacos; Neuronas/metabolismo; Neuronas/patología; Fármacos Neuroprotectores/química; Células PC12; Ratas; Ratas Sprague-Dawley; Sustancia Negra/efectos de los fármacos; Sustancia Negra/metabolismo; Sustancia Negra/patología; Resultado del Tratamiento

Palabras clave

Aceglutamide; TNF receptor associated factor 1 (TRAF1); apoptosis; cerebral ischemia and reperfusion; motor function; neuroprotection; substantia nigra

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Isquemia Encefálica / Fármacos Neuroprotectores / Glutamina / Trastornos del Movimiento Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Restor Neurol Neurosci Asunto de la revista: NEUROLOGIA Año: 2015 Tipo del documento: Article Pais de publicación: Países Bajos

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