Increased nitric oxide synthesis is not involved in delayed cerebral energy failure following focal hypoxic-ischemic injury to the developing brain.
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.
Blumberg
R M
RM
Division of Paediatrics, Obstetrics and Gynaecology, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Taylor
D L
DL
Yue
X
X
Aguan
K
K
Mckenzie
J
J
Cady
E B
EB
Weiner
C P
CP
Mehmet
H
H
Edwards
A D
AD
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
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester