Activation of autophagy and its role in the neuronal and astrocytic cell death and survival in ischemic brain injury

Hui-ling Zhang

Department of Pharmacology, Soochow University School of Medicine, Suzhou, China

Autophagy is a highly regulated cellular mechanism degrading long-lived proteins and dysfunctional organelles which seems to be implicated in a variety of physiological and pathological conditions relevant to neurological diseases. Recent studies from our lab and others indicate the existence of autophagy in cerebral ischemia, not only in ischemic neurons, but also in ischemic astrocytes, two important cell types in the brain. We propose that physiological levels of autophagy, presumably caused by mild to modest hypoxia or ischemia, appear to be protective. On the other hand, high levels of autophagy caused by severe hypoxia or ischemia and/ or reperfusion may cause self-digestion and eventual neuronal or astrocytic cell death. In addition, oxidative and endoplasmic reticulum (ER) stresses, and excitotoxicity in cerebral hypoxia or ischemia and/ or reperfusion are potent stimuli of autophagy in neurons and astrocytes. Finally, an increasing evidence suggests a considerable overlap between autophagy and apoptosis, and between autophagy and necrosis, or necroptosis in determining the outcomes and final morphology of damaged neurons and astrocytes. Therefore, a profound understanding of the biological effects and the mechanisms underlying ischemia-induced autophagy in neurons and astrocytes might be helpful in seeking effective new treatment for ischemic brain injury.