Effect of thromboxane synthase inhibition on eicosanoid levels and blood flow in ischemic rat brain

L. C. Pettigrew, J. C. Grotta, H. M. Rhoades, K. K. Wu

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Reperfusion of ischemic brain is associated with production of thromboxane A2 (TXA2), a proaggregatory vasoconstrictor. We used an animal model of transient forebrain ischemia to study the effects of 1-benzylimidazole (1-BI), a selective inhibitor of thromboxane synthase, upon cerebral elcosanoid levels and cerebral blood flow. Male Wistar rats were subjected to 30 minutes of four-vessel occlusion. The mean±SEM brain level of TXB2, the stable metabolite of TXA2, determined after 60 minutes of reperfusion was 101±20 pg/mg brain protein in five ischemic control rats. Infusion of 10 μg/g 1-BI reduced mean±SEM cerebral TXB2 concentration to 11±3 pg/mg brain protein in five rats (p≤0.002). Mean±SEM hemispheric cerebral blood flow measured in four ischemic control rats after 60 minutes of reperfusion was 42±9 ml/100 g brain/min compared with 104±13 ml/100 g brain/min in three 1-BI-treated rats (p≤0.001). Mean±SEM hippocampal blood flow in four ischemic control rats after 60 minutes of reperfusion was 51±14 ml/100 g brain/min compared with 125±25 ml/100 g brain/min in three 1-BI-treated rats (p≤0.04). We conclude that selective inhibition of thromboxane synthase may alleviate ischemic brain damage by reducing cerebral TXA2 concentrations and elevating cerebral blood flow.

Original languageEnglish
Pages (from-to)627-632
Number of pages6
JournalStroke
Volume20
Issue number5
DOIs
StatePublished - May 1989

Funding

FundersFunder number
National Institute of Neurological Disorders and StrokeP50NS023327

    Keywords

    • Cerebral blood flow
    • Cerebral ischemia
    • Rats
    • Thromboxane synthase

    ASJC Scopus subject areas

    • Clinical Neurology
    • Cardiology and Cardiovascular Medicine
    • Advanced and Specialized Nursing

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