TY - JOUR
T1 - Beneficial Effects of Acute Intravenous Ibuprofen on Neurologic Recovery of Head-Injured Mice
T2 - Comparison of Cyclooxygenase Inhibition with Inhibition of Thromboxane A2 Synthetase or 5-Lipoxygenase
AU - Hall, Edward D.
PY - 1985
Y1 - 1985
N2 - 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 F2α, thromboxane A2) and oxygen-free radical-induced lipid peroxidation.
AB - 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 F2α, thromboxane A2) and oxygen-free radical-induced lipid peroxidation.
KW - Concussive head injury–Ibuprofen–Prostaglandin F–Thromboxane–Prostacyclin– Lipid peroxidation
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U2 - 10.1089/cns.1985.2.75
DO - 10.1089/cns.1985.2.75
M3 - Article
C2 - 3938345
AN - SCOPUS:0022342554
SN - 0737-5999
VL - 2
SP - 75
EP - 81
JO - Central Nervous System Trauma
JF - Central Nervous System Trauma
IS - 2
ER -