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Severe global cerebral ischemia-induced programmed necrosis of hippocampal CA1 neurons in rat is prevented by 3-methyladenine: a widely used inhibitor of autophagy.
Wang, Jin-Ye; Xia, Qiang; Chu, Ke-Tan; Pan, Jie; Sun, Li-Na; Zeng, Bin; Zhu, Yu-Jin; Wang, Qian; Wang, Kai; Luo, Ben-Yan.
Afiliación
  • Wang JY; Department of Neurology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
J Neuropathol Exp Neurol ; 70(4): 314-22, 2011 Apr.
Article en En | MEDLINE | ID: mdl-21412169
The true programmed mechanisms of delayed neuronal death induced by global cerebral ischemia/reperfusion injury remain incompletely characterized. Autophagic cell death and programmed necrosis are 2 kinds of programmed cell death distinct from apoptosis. Here, we studied the death mechanisms of hippocampal cornu ammonis 1 neuronal death after a 20-minute severe global ischemia/reperfusion injury in young adult rats and the effects of 3-methyladenine (3-MA), a widely used inhibitor of autophagy. The morphological changes detected by electron microscopy, together with the activation of autophagy, transferase-mediated UTP nick end-labeling-positive neurons, and delayed death, demonstrated that cornu ammonis 1 neuronal death induced in this paradigm was programmed necrosis. No significant activation of caspase-3 after injury was detected by Western blot and immunohistochemistry. Treatment with 3-MA provided time-dependent protection against cornu ammonis 1 neuronal death at 7 days of reperfusion when it was administered before ischemia; administration 60 minutes after reperfusion was not beneficial. The redistribution of the lysosomal enzyme cathepsin B after injury was inhibited by 3-MA administered before ischemia, suggesting that this might be another important mechanism for the protective effect of 3-MA in ischemic neuronal injury.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenina / Isquemia Encefálica / Región CA1 Hipocampal / Neuronas Límite: Animals Idioma: En Revista: J Neuropathol Exp Neurol Año: 2011 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenina / Isquemia Encefálica / Región CA1 Hipocampal / Neuronas Límite: Animals Idioma: En Revista: J Neuropathol Exp Neurol Año: 2011 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido