Neurons are different from other cells in that they are postmitotic and not replaced after they are lost. The CNS is thus particularly vulnerable to neuronal cell loss from various causes, including ischemic injury. Recent observations show that apoptosis is a common feature in neurons dying of ischemic injury. Free radicals have been implicated in the pathogenesis of ischemic brain injury. Reperfusion after cerebral ischemia is accompanied by excessive free radical formation. Many of these free radicals are reactive oxygen species and cause oxidative damage to DNA. The base-excision repair pathway is believed to repair oxidative DNA damage in the brain after ischemia-reperfusion. We review recent laboratory findings that provide evidence of free radical-induced DNA damage and repair after ischemic injury. The polymerase responsible for replication during base-excision repair, DNA polymerase-β, lacks proofreading activity and is considered error prone. This may lead to the accumulation of DNA damage and genomic instability, probable causes of accelerated neuronal aging. A number of DNA repair genes, including ataxia teleangiectasia, p53, and poly(ADP-ribose) polymerase, are activated after DNA damage. The pathogenetic roles of these genes in ischemia-induced neuronal apoptosis are under active investigation. NEUROSCIENTIST 4:88-95, 1998
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