NEUROPROTECTIVE EFFECTS OF GINKGO-BILOBA CONSTITUENTS

The neuroprotective effects of Ginkgo biloba extract (EGb 761) and som e of its constituents were tested by using the mouse and the rat model of focal cerebral ischemia, the rat model of global cerebral ischemia and primary cultures of neurons obtained from newborn rat hippocampi and chick embryo telencephalic hemispheres. In the models of focal isc hemia, 2 days after occlusion of the middle cerebral artery the infarc t area on the mouse brain surface and the infarct volume of the rat br ain were measured. The infarct area on the mouse brain was dose-depend ently (5-20 mg/kg, s.c.) reduced by bilobalide administered 60 min bef ore ischemia. When administered immediately after ischemia, 10 mg/kg b ilobalide also diminished the infarct area. The same dose of bilobalid e administered to rats 60 min before occluding the middle cerebral art ery reduced the cortical and the total infarct volume significantly. G inkgolide A (50 mg/kg, s.c.) and ginkgolide B (100 mg/kg, s.c.) also h ad cerebroprotective effects in the mouse model of focal cerebral isch emia, but ginkgolides C and J did not. EGb 761 (2 x 100 mg/kg,i.v.) in creased the cerebral blood flow after 10 min of global ischemia in rat s but neuroprotection was not demonstrable. Ginkgolide B (1 mu M) and bilobalide (10 mu M) were shown to protect cultured rat hippocampal ne urons against damage caused by glutamate. Bilobalide (0.1 mu M) also e nhanced the percentage of viable neurons in primary cultures from chic k embryo hemispheres when damaged with 1 mM cyanide. The results demon strate different types of neuroprotective and cerebrovascular effects of the Ginkgo biloba extract and some of its constituents.