Cerebrovasodilatory contribution of endogenous carbon monoxide during seizures in newborn pigs

Massroor Pourcyrous, Henrietta S. Bada, Helena Parfenova, Michael L. Daley, Sheldon B. Korones, Charles W. Leffler

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Carbon monoxide (CO) and the excitatory amino acid glutamate both dilate cerebral arterioles in newborn pigs. The key enzyme in CO synthesis is heme oxygenase, which is highly expressed in neurons with glutamatergic receptor activity as well as cerebral microvessels. During seizures the extracellular level of glutamate is increased, which results in excessive depolarization of neurons. We hypothesized that CO is a mediator of excitatory amino acid-induced dilation of the cerebral microvasculature during seizures. Three groups of piglets were examined: 1) i.v. normal saline (sham control), 2) topical chromium mesoporphyrin (Cr-MP, 15 × 10-6M), and 3) i.v. tin-protoporphyrin (Sn-PP, 4 mg/kg). Synthetic metalloporphyrins (Cr-MP and Sn-PP) are heme oxygenase inhibitors, thereby reducing CO synthesis. Implanted closed cranial windows were used to monitor changes in pial arteriolar diameters. Seizures were induced by administration of i.v. bicuculline. Changes in pial arteriolar diameters were monitored during 30 min of status epilepticus. The percent increase in pial arteriolar dilation in the saline group during seizures was 68 ± 3%. In the metalloporphyrin groups, the pial arteriolar dilation was markedly reduced (35 ± 3% and 13 ± 1%, for Cr-MP and Sn-PP, respectively; p < 0.05, compared with the saline group). We conclude that metalloporphyrins by inhibition of heme oxygenase and prevention of CO synthesis attenuate pial arteriolar dilation during seizures. Therefore, CO appears to be involved in cerebral vasodilation caused by glutamatergic seizures.

Original languageEnglish
Pages (from-to)579-585
Number of pages7
JournalPediatric Research
Issue number5
StatePublished - 2002

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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