EFFECTS OF EGB-761 ON FATTY-ACID REINCORPORATION DURING REPERFUSION FOLLOWING ISCHEMIA IN THE BRAIN OF THE AWAKE GERBIL

Transient cerebral ischemia (5 min) releases unesterified fatty acids from membrane phospholipids, increasing brain concentrations of fatty acids for up to 1 h following reperfusion. To understand the reported anti-ischemic effect of Ginkgo biloba extract (EGb 761), we monitored its effect on brain fatty acid reincorporation in a gerbil-stroke mode l. Both common carotid arteries in awake gerbils were occluded for 5 m in, followed by 5 min of reperfusion. Animals were infused intravenous ly with labeled arachidonic (AA) or palmitic acid (Pam), and rates of incorporation of unlabeled fatty acid from the brain acyl-CoA pool wer e calculated by the model of Robinson et al. (1992), using quantitativ e autoradiography and biochemical analysis of brain acyl-CoA. Animals were treated for 14 d with 50 or 150 mg/kg/d EGb 761 or vehicle. Ische mia-reperfusion had no effect on the rate of unlabeled Pam incorporati on into brain phospholipids from palmitoyl-CoA; this rate also was una ffected by EGb 761. In contrast, ischemia-reperfusion increased the ra te of incorporation of unlabeled AA from brain arachidonoyl-CoA by a f actor of 2.3-3.3 compared with the control rate; this factor was furth er augmented to 3.6-5.0 by pretreatment with EGb 761. There is selecti ve reincorporation of AA compared with Pam into brain phospholipids fo llowing ischemia. EGb 761 further accelerates AA reincorporation, pote ntially reducing neurotoxic effects of prolonged exposure of brain to high concentrations of AA and its metabolites.