Infarct volume and functional outcome after pre- and postoperative administration of metyrapone, a steroid synthesis inhibitor, in focal brain ischemia in the rat

High blood levels of glucocorticoids are associated with increased mortalit y, confusion and poor functional outcome in stroke patients. It has been pr oposed that inhibition of glucocorticoids in acute stroke might be benefici al, but experimental data are conflicting and no long-term follow-up study has been reported. We have studied whether pre- or postoperative administra tion of metyrapone, a steroid synthesis inhibitor, can influence long-term outcome after ligation of the right middle cerebral artery (MCA) distal to the striatal branches in hypertensive rats. Metyrapone (200 mg/kg) was admi nistered either 30 min before or 1, 12 and 24 h after MCA occlusion. Limb p lacements and ability to traverse a rotating pole were evaluated pre- and p ostoperatively. Infarct size, histology and GFAP immunoreactivity were eval uated on 5 mu m coronal sections from brains perfused in situ 4 weeks after the ischemic event. Pretreatment did not influence outcome, whereas postop erative administration of metyrapone significantly increased infarct volume (P < 0.05). Posttreated rats performed significantly worse than vehicle-tr eated rats on the rotating pole 3 weeks after the operation (P < 0.05). Our results do not support the hypothesis that inhibition of glucocorticoid sy nthesis improves outcome after cerebral ischemia. Eur J Neurol 6:481-486 (C ) 1999 Lippincott Williams & Wilkins.