Title: Elibol B, Soylemezoglu F, Unal I, et al. Nitric oxide is involved in ischemia-induced apoptosis in brain: a study in neuronal nitric oxide synthase null mice.
Abstract: Elibol B, Soylemezoglu F, Unal I, et al. Nitric oxide is involved in ischemia-induced apoptosis in brain: a study in neuronal nitric oxide synthase null mice. Neurosci 2001;105:79–86. The goal of the authors was to investigate the relationship between nitric oxide apoptosis after ischemia. They compared the results of permanent unilateral middle cerebral artery occlusion in normal mice to those of mutant mice lacking the gene for neuronal nitric oxide synthase (those with a deficiency in neuronal nitric oxide production). The mean infarct area was significantly reduced in mutant mice at 6, 24, 72 hours after artery occlusion. The number of apoptotic neurons as assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL, a marker of DNA fragmentation) by caspase-3 mediated cleavage of actin to fractin was significantly reduced (50%) in mutant mice as compared with wild type mice at 72 hours. This held true after normalization for the smaller infarct size in mutant mice. Also the level of Bcl-2 an anti-apoptotic protein was significantly decreased (73%) in the ischemic hemisphere (versus the nonischemic control hemisphere) of wild type mice was significantly increased (105%) in the ischemic hemisphere (versus the contralateral hemisphere) in mutant mice. Levels of the pro-apoptotic protein Bax were unchanged in the ischemic hemispheres of mutant wild type mice. The authors propose that deficiency in neuronal nitric oxide production slows the development of apoptotic cell death after ischemia.