Enteral supplements of a carbon monoxide donor CORM-A1 protect against cerebrovascular dysfunction caused by neonatal seizures

Jianxiong Liu, Alexander L. Fedinec, Charles Leffler, Elena Parfenova

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Cerebral blood flow dysregulation caused by oxidative stress contributes to adverse neurologic outcome of seizures. A carbon monoxide (CO) donor CORM-A1 has antioxidant and cytoprotective properties. We investigated whether enteral supplements of CORM-A1 can improve cerebrovascular outcome of bicuculline-induced seizures in newborn piglets. CORM-A1 (2 mg/kg) was given to piglets via an oral gastric tube 10 minutes before or 20 minutes after seizure onset. Enteral CORM-A1 elevated CO in periarachnoid cerebrospinal fluid and produced a dilation of pial arterioles. Postictal cerebral vascular responses to endothelium-, astrocyte-, and vascular smooth muscle-dependent vasodilators were tested 48 hours after seizures by intravital microscopy. The postictal responses of pial arterioles to bradykinin, glutamate, the AMPA receptor agonist quisqualic acid, ADP, and heme were greatly reduced, suggesting that seizures cause injury to endothelial and astrocyte components of the neurovascular unit. In contrast, in the two groups of piglets receiving enteral CORM-A1, the postictal cerebral vascular responsiveness to these dilators was improved. Overall, enteral supplements of CORM-A1 before or during seizures offer a novel effective therapeutic option to deliver cytoprotective mediator CO to the brain, reduce injury to endothelial and astrocyte components of cerebral blood flow regulation and to improve the cerebrovascular outcome of neonatal seizures.

Original languageEnglish (US)
Pages (from-to)193-199
Number of pages7
JournalJournal of Cerebral Blood Flow and Metabolism
Volume35
Issue number2
DOIs
StatePublished - Feb 2 2015

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Carbon Monoxide
Small Intestine
Seizures
Cerebrovascular Circulation
Astrocytes
Arterioles
Blood Vessels
Quisqualic Acid
AMPA Receptors
Bicuculline
Glutamate Receptors
Bradykinin
sodium boranocarbonate
Heme
Vasodilator Agents
Vascular Smooth Muscle
Adenosine Diphosphate
Brain Injuries
Nervous System
Endothelium

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Enteral supplements of a carbon monoxide donor CORM-A1 protect against cerebrovascular dysfunction caused by neonatal seizures. / Liu, Jianxiong; Fedinec, Alexander L.; Leffler, Charles; Parfenova, Elena.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 35, No. 2, 02.02.2015, p. 193-199.

Research output: Contribution to journalArticle

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