LAU-0901, a novel platelet-activating factor receptor antagonist, confers enduring neuroprotection in experimental focal cerebral ischemia in the rat

Abstract

LAU-0901, a novel platelet-activating factor (PAF) receptor antagonist, is highly neuroprotective in a rodent model of cerebral ischemia. This study was conducted to establish whether the neuroprotection induced by LAU-0901 persists with chronic survival. Male Sprague–Dawley rats were anesthetized with isoflurane and subjected to 2 h of temporary middle cerebral artery occlusion (MCAo) induced by means of a poly-l-lisine-coated intraluminal nylon suture. Animals were treated with either LAU-0901 (60 mg/kg) or vehicle (45% cyclodextran) administered i.p. at 2 h from onset of MCAo. They received neurobehavioral examinations during MCAo (60 min) and then at 1, 2, 3, 7, 14, 21 and 28 days followed by histopathology at 30 days. LAU-0901 significantly improved the behavior compared to the vehicle group, beginning on day 1 (by 29%, p = 0.00007) and persisting throughout a 30-day survival period (42%, p = 0.0001). Compared with vehicle treatment, LAU-0901 treatment significantly increased volume of non-infarcted brain tissue loss relative to the unlesioned hemisphere (16.3 ± 4.6% vs. 46.0 ± 10.3%, respectively). These results establish that LAU-0901 confers enduring ischemic neuroprotection.