A nitric oxide donor induces neurogenesis and reduces functional deficits after stroke in rats

The adult rodent brain is capable of generating neuronal progenitor cells i n the subventricular zone, and in the dentate gyrus of the hippocampus, thr oughout the life of the animal. Signals that regulate progenitor cell proli feration, differentiation, and migration are not well known. We report that administration of a nitric oxide donor; W-1-[N-(2-aminoethyl)-N (2-ammonio ethyl) aminio]diazen-1-ium-1,2-diolate (DETA/NONOate), to young adult rats significantly increases cell proliferation and migration in the subventricu lar zone and the dentate gyrus. Treatment with DETA/NONOate also increases neurogenesis in the dentate gyrus. Furthermore, administration of DETA/NONO ate to rats subjected to embolic middle cerebral artery occlusion significa ntly increases cell proliferation and migration in the subventricular zone and the dentate gyrus, and these rats exhibit significant improvements of n eurological outcome during recovery from ischemic stroke. Administration of DETA/NONOate significantly increases cortical levels of guanosine monophos phate both in ischemic and nonischemic rats, supporting the role of nitric oxide in promoting cell proliferation and neurogenesis. Thus, our data indi cate that nitric oxide is involved in the regulation of progenitor cells an d neurogenesis in the adult brain. This suggests that nitric oxide delivere d to the brain well after stroke may have therapeutic benefits.