Neuroprotection from Focal Ischemia by 4-Phenyl-1-(4-Phenylbutyl) Piperidine (PPBP) Is Dependent on Treatment Duration in Rats

Abstract

The IV administration of the potent sigma1-receptor ligand 4-phenyl-1-(4-phenylbutyl)piperidine (PPBP) provides neuroprotection against focal cerebral ischemia. We tested the hypothesis that prolonged, continuous administration of PPBP would provide further neuroprotection in a rat model of transient focal ischemia and reperfusion. Under controlled conditions of normoxia, normocarbia, and normothermia, halothane-anesthetized male Wistar rats were subjected to 2 h of middle cerebral artery occlusion by the intraluminal occlusion technique. Sixty minutes after the onset of ischemia, rats were randomly assigned to six treatment groups to receive a continuous IV infusion of PPBP (1 [micro sign]mol [center dot] kg-1 [center dot] h-1) for 1, 2, 3, or 4 days or saline for 1 or 4 days. The infarction volume was assessed by triphenyltetrazolium chloride (TTC) staining on Day 4 after ischemia in all rats. The TTC-determined infarction volume of the ipsilateral cerebral cortex was smaller in rats treated with PPBP for 1 day (42 +/- 13 mm3; 10% +/- 3% of ipsilateral hemisphere; P (Anesth Analg 1998;87:1299-305)