Effect of propentofylline (HWA 285) on focal ischemia in rats: effect of treatment and posttreatment duration on infarct size.
BACKGROUND AND PUROSEe: in this study we tested the potentially neuroprotective properties of propentofylline in a model of focal ischemia with long-term, repeated treatment.


METHODS
37 male Wistar rats (280-300 g) underwent permanent occlusion of the middle cerebral artery (MCA). Infusion was started 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 repetitive intraperitoneal injections were started. Animals were assigned to four groups: continuous treatment for a period of 12 h with 24-h survival (group A, n=9) or 48-h survival (group B, n=10), continuous treatment for a period of 48 h with 48-h survival (group C, n=9) and placebo (group D, n=9). Infarct size was calculated from brain slices stained with 2,3,5-triphenyltetrazolium chloride.


RESULTS
the infarct size was significantly reduced in group C (treatment for 48 h) (163.9+/-30.5 mm(3)) compared to the placebo group (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 (239.6+/-42.9 mm(3)) compared to placebo.


CONCLUSIONS
continuous i.p. injections of propentofylline over a period of 48 h significantly reduces infarct size in an animal model of focal cerebral ischemia. With shorter periods of continuous administration of the drug and 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 the beneficial effects of neuroprotection by propentofylline.
Haag
P
P
Department of Neurology, University of Heidelberg, Germany. ps.haag@t-online.de
Schneider
T
T
Schäbitz
W
W
Hacke
W
W
D000818:Animals; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010919:Placebos / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D016896:Treatment Outcome; D014970:Xanthines / Q000494:pharmacology*
D018696:Neuroprotective Agents; D010919:Placebos; D014970:Xanthines; C032114:propentofylline