Involvement of platelet-activating factor (PAF) in cerebral post-ischemic phase in Mongolian gerbils.
Platelet-activating factor (PAF) is a potent mediator of anaphylaxis and shock. In addition, evidence for PAF participation in gastric, intestinal and heart post-ischemic phase has been recently demonstrated. Ginkgo biloba extracts improve cerebral metabolism and protect brain against hypoxic damage in various models of cerebral ischemia. Potent and specific antagonists of PAF have been found in Ginkgo biloba and termed Ginkgolides: BN 52020, BN 52021, BN 52022, BN 52024. We therefore undertook the investigation of the role of Ginkgolides in cerebral ischemia obtained by bilateral ligature of the common carotid for 10 min and 6 h of recirculation in male Mongolian adult gerbils. Given preventively (one week treatment 10 mg/kg/day orally) or at the time of clamping, BN 52021 and related Ginkgolides dose-dependently antagonize morbidity assessed by the stroke-index. Similarly the mitochondrial respiration evaluated by the respiratory control ratio is significantly improved. In both determinations, the range of activity: BN 52021 greater than, BN 52020 greater than BN 52022 greater than BN 52024 shows that the effect of Ginkgolides in cerebral ischemia are correlated with their PAF antagonistic properties. Given curatively, 1 h after declamping, BN 52021 is able to reverse the cerebral impairment trend. Kadsurenone and brotizolam, two other chemically unrelated PAF antagonists led to similar recovery. Therefore PAF appears to play an important role in the post-ischemic phase after bilateral carotid ligation in Mongolian gerbils.
IHB Research Labs, Le Plessis Robinson, France.
B
B
Spinnewyn
N
N
Blavet
F
F
Clostre
N
N
Bazan
P
P
Braquet
D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology* / Q000517:prevention & control; D002339:Carotid Arteries / Q000502:physiology; D004224:Diterpenes; D005849:Gerbillinae; D046934:Ginkgolides; D007783:Lactones; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010936:Plant Extracts / Q000627:therapeutic use*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D013329:Structure-Activity Relationship
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; D010972:Platelet Activating Factor; C045856:ginkgolide B