Differential variations of autophagy and apoptosis in permanent focal cerebral ischaemia rat model

Abstract

ABSTRACTObjective: Autophagy and apoptosis coexist in stroke, but the relationship between effects and complex is poorly understood. Herein, we investigated dynamic changes of autophagy and apoptosis at the penumbra in permanent cerebral ischaemia. Methods: Sprague-Dawley rat models were prepared by middle cerebral artery occlusion. The autophagy and apoptosis were evaluated by Western blotting and immunofluorescence with LC3-II and cleaved caspase-3, respectively. The neurological deficit score and infarct volume were assessed. Results: The results showed that the expressions of LC3-II and cleaved caspase-3 were gradually increased from 1 to 5 hours, and reached maximum at 5 hours after stroke. After that, LC3-II expression was significantly declined, but cleaved caspase-3 expression was only mildly reduced from 6 hours to 3 days. Surprisingly, at 4 days after stroke, the autophagy was abruptly increased again, but the apoptosis was considerably and continuously decreased. The severity of the neurological deficit was in accordance with the increase of infarct expansion. Conclusions: Our results showed that autophagy and apoptosis were simultaneously activated within 12 hours after stroke. Four days later, LC3-II expression was significantly increased, while cleaved caspase-3 expression was considerably decreased, implying that there might be a transition from apoptosis to autophagy at the subacute phase of stroke.