Effect of propentofylline (HWA 285) on focal ischemia in rats: Effect of treatment and posttreatment duration on infarct size

Background and purpose: in this study we tested the potentially neuroprotec tive properties of propentofylline in a model of focal ischemia with long-t erm repeated treatment. Methods: 37 male Wistar rats (280-300 g) underwent permanent occlusion of the middle cerebral artery (MCA). Infusion was start ed 30 min after occlusion of the MCA over a period of 2 h with a dosage of 0.01 mg/kg body weight. Immediately after the termination of infusion repet itive intraperitoneal injections were started. Animals were assigned to fou r groups: continuous treatment for a period of 12 h with 24-h survival (gro up AI n=9 or 48-h survival (group B, n=10), continuous treatment for a peri od of 48 h with 48-h survival (group C, n=9) and placebo (group D, n=9). In farct size was calculated from brain slices stained with 2,3,5-triphenyltet razolium chloride. Results: the infarct size was significantly reduced in g roup C (treatment for 48 h) (163.9+/-30.5 mm(3)) compared to the placebo gr oup (297.4+/-17.7 mm(3)). No effect on infarct size was observed in group A (196.8+/-37.3 mm(3)) and group B (239.6142.9 mm(3)) compared to placebo. C onclusion: continuous i.p. injections of propentofylline over a period of 4 8 h significantly reduces infarct size in an animal model of focal cerebral ischemia. With shorter periods of continuous administration of the drug an d delayed postmortem analysis, reductions in the infarct size did not reach a level of significance. These data show the importance of continuous long -term administration after ischemic stroke in clinical trials to achieve th e beneficial effects of neuroprotection by propentofylline. (C) 2000 Elsevi er Science B.V. All rights reserved.