Commentary Eaten Alive Autophagy and Neuronal Cell Death after Hypoxia-lschemia

摘要

Hypoxic-ischemic injury to the brain is a major cause of morbidity and mortality in infants and adults. Despite advances in obstetric care, the incidence of cerebral palsy from perinatal hypoxia-ischemia remains at >2 per 1000 births,1 and arterial ischemic stroke occurs in ? of 4000 term infants.2 In the United States, stroke is the third leading cause of death in adults (Centers for Disease Control and Prevention National Center for Health Statistics), and hypoxic-ischemic brain injury can be prominent in survivors of cardiac arrest, the leading cause of death. As with any pathological insult, multiple pathways of injury and adaptation are activated after hypoxic-ischemic brain injury. Delineating positive and negative contributions of these pathways to neuronal cell loss is critical for development of neuroprotective therapies but can be exceedingly difficult to detangle. Dying neurons in the ischemic brain exhibit a range of morphologies ascribed to apoptotic, autophagic, and oncotic (necrotic) cell death pathways,3 although the role of autophagy as a mediator of cell death has been controversial.4'5 In this issue of The American Journal of Pathology, Koike and colleagues6 present the first in vivo evidence of neuronal cell death requiring autophagy in the mammalian brain.#1 Dollars 1001N200306464Dollars 1200