Preventing Harmful Effects of Epileptic Seizures on Cerebrovascular Functions in Newborn Pigs: Does Sex Matter?

BACKGROUND: The potential contribution of sex-related variables to cerebrovascular functions in neonates remains elusive. Newborn piglets provide a translationally relevant model for studying the effects of seizures in the neonatal brain. The present study investigated whether sex differences contribute to cerebrovascular functions in healthy and epileptic newborn pigs. METHODS: Epileptic seizures were induced in female and male newborn pigs by bicuculline. An antioxidant drug, the carbon monoxide-releasing molecule CORM-A1, was administered enterally before or during seizures. The responses of pial arterioles to endothelium-, astrocyte-, and vascular smooth muscle-dependent vasodilators were tested in intact and 48-h postictal piglets using the cranial window technique. RESULTS: In intact newborn pigs, we did not observe any sex-related differences in cerebrovascular functions. In the postictal male and female newborn pigs, a dramatic reduction in responses of pial arterioles to endothelium- and astrocyte-dependent vasodilators was detected. CORM-A1, administered before or during seizures, greatly improved the outcome of seizures on cerebrovascular functions in both male and female piglets. CONCLUSION: We found no evidence of sex-related differences in cerebral vasodilator functions in control and epileptic newborn pigs. In both male and female newborns, epileptic seizures lead to prolonged cerebral vascular dysfunction that is effectively prevented by CORM-A1 therapy.