Expression of inducible nitric oxide synthase after focal cerebral ischemia stimulates neurogenesis in the adult rodent dentate gyrus.
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.
Zhu
Dong Ya
DY
Department of Physiology and Biophysics, Neuroscience Research Group, Faculty of Medicine, University of Calgary, Calgary, Canada, T2N 4N1.
Liu
Shu Hong
SH
Sun
Hong Suo
HS
Lu
You Ming
YM
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002545:Brain Ischemia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002455:Cell Division; D018891:Dentate Gyrus / Q000166:cytology* / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017353:Gene Deletion; D049452:Green Fluorescent Proteins; D007700:Kinetics; D008164:Luminescent Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology* / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D004791:Enzyme Inhibitors; D008164:Luminescent Proteins; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat