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

Autophagy. 2009 Feb;5(2):221-3. doi: 10.4161/auto.5.2.7363. Epub 2009 Feb 7.

Abstract

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), which inhibit autophagy, significantly reduced autophagic pathway activation and switched the mechanism of cell death from apoptotic to necrotic. Rapamycin, conversely, which increases autophagy, reduced necrotic cell death, and decreased brain injury. A prophylactic treatment with simvastatin or hypoxic preconditioning also caused upregulation of autophagic pathways. In this addendum, we summarize these findings and speculate on the possible physiological role of autophagy during hypoxia-ischemia induced neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy*
  • Brain Injuries / pathology*
  • Hypoxia-Ischemia, Brain / pathology*
  • Models, Biological*
  • Protein Kinases / metabolism
  • Rats
  • TOR Serine-Threonine Kinases

Substances

  • Protein Kinases
  • TOR Serine-Threonine Kinases