On ischemic brain injury in genetically altered mice.

In recent years, genetically altered mice, either overexpressing or deficient in specific gene products, have come to play a vital role in experimental studies designed to probe the molecular pathophysiology of ischemic brain injury. More than 100 such studies have been reported to date, and notable successes have been achieved in elucidating the roles of the neuronal,1,2 endothelial,3 and inducible4,5 isoforms of nitric oxide synthase and of the cytosolic (CuZn)6–8 and mitochondrial (Mn) forms9–11 of the antioxidant-defense enzyme superoxide dismutase in brain ischemia. Other studies of cerebral ischemia have used mutant mice to assess altered glutamate-receptor subunit composition,12,13 vascular adhesion molecules,14–19 gene products related to nuclear damage, cell death and survival, apoptosis,20–23 transcription factors and early-response genes,24–27 cytokines,28,29 and apolipoprotein E.30,31