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The Journal of Neuroscience, January 1, 2003, 23(1):223-229
Expression of Inducible Nitric Oxide Synthase after Focal Cerebral Ischemia Stimulates Neurogenesis in the Adult Rodent Dentate Gyrus
Dong Ya Zhu, Shu Hong Liu, Hong Suo Sun, and You Ming Lu Department of Physiology and Biophysics, Neuroscience Research Group, Faculty of Medicine, University of Calgary, Calgary, Canada, T2N 4N1
The generation of new neurons in the adult mammalian hippocampus is thought to play a role in repairing the brain after injury. Here, we show that 7 d after focal cerebral ischemia, newly divided cells in the dentate gyrus of adult rats increased to approximately sevenfold, compared with sham controls. In the same area, this enhanced dentate neurogenesis was associated with activation of inducible nitric oxide synthase (iNOS). Inhibition of iNOS by aminoguanidine prevented ischemia-induced neurogenesis in the dentate gyrus. In null mutant mice lacking the iNOS gene, increased neurogenesis was not observed after focal cerebral ischemia. This study demonstrates that expression of iNOS is necessary for ischemia-stimulated cell birth in the dentate gyrus and indicates that activation of iNOS may provide a possible strategy for functional recovery from cerebral ischemic insult.
Key words: neurogenesis; dentate granule neurons; focal cerebral ischemia; iNOS expression; iNOS activity; RT-PCR; green fluorescent protein
Copyright © 2003 Society for Neuroscience 0270-6474/03/231223-07$05.00/0
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