Transcripts of damaged genes in the brain during cerebral oxidative stress.

Recent studies using ischemia/reperfusion models of brain injury suggest that there is a period of time during which the formation of oxidative DNA lesions (ODLs) exceeds removal. This interval is a window of opportunity in which to study the effect of gene damage on gene expression in the brain, because the presence of excessive ODLs mimics a deficiency in gene repair, which has been shown to be associated with neurological disorders. Evidence from studies using similar models indicates that expression of faulty transcripts from ODL-infested genes and non-sense mutation in repaired genes occur before the process of cell death. Preventing the formation of ODLs and enhancing ODL repair are shown to increase the expression of intact transcripts and attenuate cell death. Understanding this mechanism could lead to the development of therapeutic techniques (physiologic, pharmacological, and/or genomic) that can enhance recovery. Copyright 2002 Wiley-Liss, Inc.