title: Increased nitric oxide synthesis is not involved in delayed cerebral energy failure following focal hypoxic-ischemic injury to the developing brain.
abstract: This study addressed the hypothesis that the delayed impairment in cerebral energy metabolism that develops 10-24 h after transient hypoxia-ischemia in the developing brain is mediated by induction of increased nitric oxide synthesis. Four groups of 14-d-old Wistar rat pups were studied. Group 1 was subjected to unilateral carotid artery ligation and hypoxia followed immediately by treatment with the nitric oxide synthase (NOS) inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg). Group 2 underwent hypoxia-ischemia but received saline vehicle. Group 3 received L-NAME without hypoxia-ischemia, and group 4, saline vehicle alone. At defined times after insult, the expression of neuronal and inducible NOS were determined and calcium-dependent and -independent NOS activities measured. Cerebral energy metabolism was observed using 31P magnetic resonance spectroscopy. At 48 h after insult, the expression of inducible NOS increased, whereas neuronal NOS at 24 h decreased on the infarcted side. Calcium-dependent NOS activity was higher than calcium-independent NOS activity, but did not increase within 36 h after insult, and was significantly inhibited by the administration of L-NAME. However, L-NAME did not prevent delayed impairment of cerebral energy metabolism or ameliorate infarct size. These results suggest that the delayed decline in cerebral energy metabolism after hypoxia-ischemia in the 14-d-old rat brain is not mediated by increased nitric oxide synthesis.
authors.affiliation: Division of Paediatrics, Obstetrics and Gynaecology, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Blumberg
authors.forename: D L
authors.initials: DL
authors.lastname: Taylor
authors.forename: X
authors.initials: X
authors.lastname: Yue
authors.forename: K
authors.initials: K
authors.lastname: Aguan
authors.forename: J
authors.initials: J
authors.lastname: Mckenzie
authors.forename: E B
authors.initials: EB
authors.lastname: Cady
authors.forename: C P
authors.initials: CP
authors.lastname: Weiner
authors.forename: H
authors.initials: H
authors.lastname: Mehmet
authors.forename: A D
authors.initials: AD
authors.lastname: Edwards
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000098:blood supply / Q000254:growth & development / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism*; D004734:Energy Metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester