Beneficial Effects of Acute Intravenous Ibuprofen on Neurologic Recovery of Head-Injured Mice: Comparison of Cyclooxygenase Inhibition with Inhibition of Thromboxane A2 Synthetase or 5-Lipoxygenase

Edward D. Hall

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38 Scopus citations

Abstract

The ability of the cyclooxygenase inhibitor ibuprofen to affect early neurologic recovery following a moderately severe concussive head injury was studied in male CF-1 mice. Each mouse received a 900 g-cm (50 g weight dropped 18 cm) head injury, followed within 5 minutes with a single IV dose of ibuprofen (sodium salt; 1, 3, 10, or 30 mg/kg). At 1 hour postinjury, their neurologic status was assessed using a grip test. Drug administration and neurologic evaluation were carried out blindly. A dose-related improvement in recovery was observed, with a 10 mg/kg IV dose causing a 122% increase in the mean grip test score compared to 0.9% saline treatment (p < 0.01 by one-way ANOVA). In addition, there was a significant decrease in the number of mice in the 10 mg/kg ibuprofen group that fell off the grip test string in 0–5 seconds (i.e., that were severely impaired). In comparison, neither the selective thromboxane A2 synthetase inhibitor furegrelate sodium, the stable epoprostenol (PGI2) analog ciprostene calcium, nor the selective 5-lipoxygenase inhibitor piriprost potassium caused any therapeutic effect. The highest dose of the TXA2 synthetase inhibitor (30 mg/kg IV) actually had a statistially significant detrimental action that appeared to be due to an increase in posttraumatic cerebral hemorrhage. The possible mechanisms of the beneficial effect of ibuprofen in acute head injury are discussed in relation to an attenuation of the synthesis of vasoactive arachidonic acid metabolites (e.g., prostaglandin F, thromboxane A2) and oxygen-free radical-induced lipid peroxidation.

Original languageEnglish
Pages (from-to)75-81
Number of pages7
JournalCentral Nervous System Trauma
Volume2
Issue number2
DOIs
StatePublished - 1985

Keywords

  • Concussive head injury–Ibuprofen–Prostaglandin F–Thromboxane–Prostacyclin– Lipid peroxidation

ASJC Scopus subject areas

  • Clinical Neurology

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