Endogenous carbon monoxide (CO), a product of heme oxygenase activity, has vasodilator and cytoprotective effects in the cerebral circulation of newborn pigs. CORM-A1 (sodium boranocarbonate) is a novel, water-soluble, CO-releasing compound. We addressed the hypotheses that: 1) CORM-A1 can deliver CO to the brain and exert effects of CO on the cerebral microvasculature, and 2) CORM-A1 is cerebroprotective. Acute and delayed effects of topically and systemically administered CORM-A1 on cerebrovascular and systemic circulatory parameters were determined in anesthetized newborn pigs with implanted closed cranial windows. Topical CORM-A1 (10-⁷M-10-⁵M) applied to the brain produced concentration-dependent CO release and pial arteriolar dilation. Systemically administered CORM-A1 (2 mg/kg, ip or iv) caused pial arteriolar dilation and increased cortical CSF CO concentration. Systemic CORM-A1 did not have acute or delayed effects on blood pressure, heart rate, or blood gases. Potential cerebroprotective vascular effects of CORM-A1 (2 mg/kg ip, 30 min before seizures) were tested 2 days after bicuculline-induced epileptic seizures (late postictal period). In control piglets, seizures caused reduction in postictal cerebral vascular responsiveness to selective physiologically relevant vasodilators, bradykinin, hemin and isoproterenol, indicative of cerebral vascular injury. In contrast, in CORM-A1-pretreated animals, no loss of postictal cerebral vascular reactivity was observed. We conclude that systemically administered CORM-A1 delivers CO to the brain, elicits the vasodilator and cytoprotective effects of CO in the cerebral circulation, has no long-term adverse effects, and protects the neonatal brain from cerebral vascular injury caused by epileptic seizures.