Molecular mechanisms of autophagic neuron death

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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. Induction of neuronal autophagy after H/I injury is generally considered neuroprotective, as it maintains cellular homeostasis. However, our recent results show that cell death of hippocampal pyramidal neurons following neonatal H/I injury is largely prevented by Atg7 deficiency. This is the first report that we are aware of providing direct evidence for autophagy-induced neuron death after neonatal mouse H/I brain injury, using mice that cannot execute autophagy specifically in CNS tissue. Thus, therapeutic strategies to inhibit autophagy-induced neuron death may prove beneficial in the treatment of both pediatric and adult H/I brain injury.