Autophagic neuron death in neonatal brain ischemia/hypoxia

Autophagy. 2008 May;4(4):404-8. doi: 10.4161/auto.5598. Epub 2008 Jan 17.

Abstract

Hypoxia/ischemia (H/I) brain injury at birth is an important cause of cerebral palsy, mental retardation, and epilepsy. The H/I insult also causes energy failure, oxidative stress, and unbalanced ion fluxes, leading to high induction of autopahgy in brain neurons. Since the mice unable to execute autophagy (due to brain-specific deletion of Atg7 or Atg5) die by massive loss of cerebral and cerebellar neurons with accumulation of ubiquitin aggregates, induction of neuronal autophagy after H/I injury is generally considered neuroprotective by maintaining cellular homeostasis. However, our recent results show that hippocampal pyramidal neurons undergoing caspase-dependent or -independent death following neonatal H/I injury possess abundant LC3-positive granules, and such H/I neuronal death is largely prevented by Atg7 deficiency. In the present review we discuss the roles of autophagy and other forms of programmed cell death in the neonatal H/I brain insult.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Autophagy*
  • Caspases / metabolism
  • Hippocampus / cytology
  • Humans
  • Hypoxia-Ischemia, Brain* / metabolism
  • Hypoxia-Ischemia, Brain* / pathology
  • Hypoxia-Ischemia, Brain* / physiopathology
  • Infant, Newborn
  • Neurons / cytology
  • Neurons / physiology*

Substances

  • Caspases