Autophagy in hypoxia-ischemia induced brain injury: Evidences and speculations

The interaction among autophagy, apoptosis and necrosis is complex and still a matter of debate. We have recently studied this interaction after neonatal hypoxia-ischemia (HI) in rats. We found that autophagic and apoptotic pathways were significantly increased at short times after HI in neuronal cells. 3-Methyladenine (3-MA) and wortmannin (WM), that inhibit autophagy, significantly reduced autophagic pathways activation and switched the mechanism of cell death from apoptotic to necrotic. Rapamycin, conversely, that increases autophagy, reduced necrotic cell death, and decreased brain injury. A prophylactic treatment with simvastatin or hypoxic preconditioning also caused up-regulation of autophagic pathways. In this Addendum, we summarize these findings and speculate on the possible physiological role of autophagy during hypoxia-ischemia induced neurodegeneration.