Nitric oxide synthase inhibition and delayed cerebral injury after severe cerebral ischemia in fetal sheep

Kyla A. Marks, Carina E. Mallard, Idris Roberts, Chris E. Williams, Peter D. Gluckman, A. David Edwards

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


After transient cerebral ischemia in fetal sheep, delayed disruptions in cerebral energetics are represented by a delayed increase in cortical impedance, a progressive decrease in the concentration of oxidized cytochrome oxidase as measured by near-infrared spectroscopy, and cortical seizures. Because the production of nitric oxide (NO), a potent mediator of neuronal death, is increased during this phase, the present study investigated whether inhibition of NO synthesis could ameliorate the delayed disruption in cerebral energetics. Eleven late gestation fetal sheep were subjected to 30 min of transient cerebral ischemia in utero. Two hours later, the treatment group (n = 5) received a continuous infusion of N(G)-nitro-L-arginine, a competitive inhibitor of NO synthase, whereas the control group (n = 6) received PBS. Changes in concentration of oxidized cytochrome oxidase, cortical impedance, and electrocortical activity were observed for 3 d. A delayed increase in cortical impedance of similar magnitude and duration commenced at 14 ± 4 h in the control and at 15 ± 3 h in the treatment groups. The progressive decrease in oxidized cytochrome oxidase signal, by - 2.2 ± 0.2 μmol/L in the control and -2.0 ± 0.4 μmol/L in the treatment group at 72 h postischemia, was similar in both groups. In both groups, delayed cortical seizures were indicated by intense low-frequency electrocortical activity. In the treatment group, duration of cortical seizures was increased and the intensity of the final electrocortical activity was more depressed (-19 ± 1 dB versus -10 ± 2 dB). The results indicate that after cerebral ischemia in fetal sheep, NO synthase inhibition does not ameliorate the delayed disruptions in cerebral energetics. However, the effect of NO synthase inhibition on delayed cortical seizures may improve our understanding of the role of NO during this phase.

Original languageEnglish
Pages (from-to)8-13
Number of pages6
JournalPediatric Research
Issue number1
StatePublished - 1 Jan 1999
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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