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.