The 2-oxopyrrolidinacetamide piracetam reduces infarct brain volume induced by permanent middle cerebral artery occlusion in male rats

In this study, the temporal development of focal cerebral infarction induced by permanent middle cerebral artery occlusion (pMCAO) and the effects of piracetam, a derivative of gamma-aininobutyric acid widely used in clinical practice as a nootropic agent, on infarct area and volume were investigated. pMCAO caused a cerebral infarct whose size progressively increased after 3, 6, 9, and 24 h. Piracetam (125 mg/ka i.p.), administered 6, 9, and 22 h after pMCAO, did not reduce pMCAO-induced brain infarct area size detected at the 24th hour. By contrast, when this agent was administered at the doses of 250 and 500 mg/kg, it caused a marked reduction of the infarct area size. This reduction was observed in almost every brain slice affected by pMCAO, although statistical differences (p <0.05) were detected in slices located at 3-5.5 mm posterior to the anterior pole in animals treated with 250 mg/kg piracetam and in slices located at 3.5-5 mm in those receiving 500 mg/kg. When the mean total volumes of brain infarct resulting from pMCAO were calculated, it was observed that in animals which had received piracetam (250 or 500 mg/kg) infarction volume was markedly (50%) and significantly (p <0.05) reduced in comparison with saline injected rats. Finally, piracetam (250 mg/kg administered i.p. 6, 9, and 22 h after the ischemic insult) significantly reduced brain infarct area evaluated 48 h and 7 days after pMCAO. (C) 2002 Elsevier Science Ltd. All rights reserved.