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 model. Both common carotid arteries in awake gerbils were occluded for 5 min, followed by 5 min of reperfusion. Animals were infused intravenously with labeled arachidonic (AA) or
palmitic acid (Pam), and rates of incorporation of unlabeled
fatty acid from the brian
acyl-CoA pool were calculated by the model of Robinson et al. (1992), using quantitative 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.
Ischemia-reperfusion had no effect on the rate of unlabeled Pam incorporation into brain
phospholipids from
palmitoyl-CoA; this rate also was unaffected by
EGb 761. In contrast,
ischemia-reperfusion increased the rate of incorporation of unlabeled AA from brain
arachidonoyl-CoA by
a factor of 2.3-3.3 compared with the control rate; this factor was further augmented to 3.6-5.0 by pretreatment with
EGb 761. There is selective reincorporation of AA compared with Pam into brain
phospholipids following
ischemia.
EGb 761 further accelerates AA reincorporation, potentially reducing neurotoxic effects of prolonged exposure of brain to high concentrations of AA and its metabolites.