Temporary focal cerebral ischemia in spontaneously hypertensive rats: the effect of ibuprofen on infarct volume

Abstract

Arachidonic acid metabolism results in the generation of oxygen radicals and production of prostanoids which are proposed to adversely influence cerebral ischemia. Inhibition of cyclooxygenase, an enzymatic step in arachidonic acid metabolism, has effected an improvement in histologic outcome after cerebral ischemia. However, there has been no attempt to determine whether this effect occurs during vascular occlusion or during reperfusion. We assessed the effect of cyclooxygenase inhibition on infarct volume in the setting of either temporary or permanent middle cerebral artery occlusion (MCAo). Rats were allotted to one of the following groups: Groups I and II, 180 min of MCAo and 120 min of reperfusion; and Groups III and IV, 180 min of permanent MCAo. In Groups I and III, vehicle only was given, whereas in Groups II and IV, ibuprofen was given throughout the study period (MCAo with or without reperfusion). After the ischemic period the brains were analyzed for infarct volume (mm3, mean +/- S.D.) by 2,3,5-triphenyltetrazolium chloride stain. For animals in which reperfusion was allowed, ibuprofen reduced infarct volume (Group I, 122 +/- 15 mm3 vs. Group II, 63 +/- 7 mm3). However, in animals with permanent MCAo, ibuprofen worsened infarct volume (Group III, 79 +/- 8 mm3 vs. Group IV, 110 +/- 13 mm3). These data suggest that the beneficial effect of cyclooxygenase inhibition occurs during reperfusion.