In vivo hypoxia-induced neuronal damage with an enhancement of neuronal nitric oxide synthase immunoreactivity in hippocampus.
Although it is well known that brain ischemia is dominantly caused by hypoxia and hypoglycemia, it is still unclear how hypoxia participates in ischemia. We studied the changes in neuronal nitric oxide synthase (nNOS) and the effect of the NOS inhibitor NG-nitro-L-arginine (NNA) on hypoxia. In vivo hypoxia (5% O2/95% N2 for 30 min) induced mild degenerative neuronal changes (shrunken and eosinophilic somata with picnotic nuclei) in neurons of the CA3, the hilus of the dentate gyrus (DG) and the DG, but not in the CA1. At 3 and 7 days after hypoxia, levels of nNOS protein were significantly enhanced to 153 and 209%, but iNOS protein could not be detected. The numbers of nNOS-immunopositive neurons were significantly enhanced to 145 and 191% in the CA3, 145 and 178% in the hilus of the DG, and 243 and 387% in the DG after 3 and 7 days, respectively. In contrast, no statistical difference was determined in the CA1. We further examined the effect of NNA administered at 5 min and 3, 6, and 24 h after hypoxia. Administration of NNA (0.1 and 1 mg/kg, i.p.) significantly decreased the number of damaged neurons in the hilus of the DG and the DG. However, higher doses of NNA (10 mg/kg, i.p.) did not prevent damage. These results suggest that hypoxia alone induces enhancement of nNOS protein and nNOS immunoreactivity in neurons of the hippocampus and that NNA has biphasic effects against hypoxia-induced neuronal damage in the hilus of the DG and the DG.
Matsuoka
Y
Y
Department of Neurobiology, Kyoto Pharmaceutical University, Japan.
Kitamura
Y
Y
Tooyama
I
I
Kimura
H
H
Taniguchi
T
T
D000818:Animals; D002467:Cell Nucleus / Q000473:pathology; D002531:Cerebellum / Q000201:enzymology; D018891:Dentate Gyrus / Q000201:enzymology / Q000473:pathology; D004804:Eosinophils / Q000473:pathology; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology*; D002534:Hypoxia, Brain / Q000201:enzymology / Q000473:pathology*; D009474:Neurons / Q000201:enzymology* / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis*; D019335:Nitroarginine / Q000494:pharmacology; D017966:Pyramidal Cells / Q000201:enzymology / Q000473:pathology; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D019335:Nitroarginine; D019001:Nitric Oxide Synthase