Effects of delayed administration of methohexital and ketamine on posthypoxic cell damage of primary neuronal cultures.

Primary neuronal cultures from chick embryo cerebral hemispheres received NaCN (cytotoxic hypoxia) for 120 min and were then allowed to recover. Methohexital (300 mumol/l) or ketamine (30 mumol/l) given either before or during the hypoxic period elevated adenosine triphosphate (ATP) content of the cultures 15 min after hypoxia. Prehypoxic administration of ketamine also preserved the structural integrity and ATP content of neurons 20 h later, while methohexital did not. Ketamine elevated ATP content as measured 20 h after hypoxia even when administered 15 min after beginning of recovery. Pharmacokinetic reasons for contradictory effects of ketamine on neuronal cell loss in vivo ischemia studies and our in vitro experiments are discussed.

PAF antagonist ginkgolide B reduces postischemic neuronal damage in rat brain hippocampus.

We investigated the effect of the known antagonist of platelet-activating factor (PAF), ginkgolide B, on postischemic neuronal damage in the rat. Neuronal necroses were evaluated in the hippocampus 7 days after a 10-min forebrain ischemia. Preischemic application of ginkgolide B (50 mg/kg p.o.) significantly reduced neuronal damage. It is suggested that the antagonism of PAF is responsible for this beneficial effect of ginkgolide B.

Effects of Ginkgo biloba constituents related to protection against brain damage caused by hypoxia.

The purpose of the present study was to approach the compound(s) responsible for the beneficial effects of an extract of Ginkgo biloba leaves (EGB) on animals subjected to hypoxia. In this first approach we compared the effects of the flavone and the non-flavone fraction of EGB with those of the whole extract on mice in lethal hypoxia (3.5% O2), on brain energy metabolism of artificially ventilated rats inspiring 7% O2, and on local cerebral blood flow (LCBF) of normoxic rats. The latter two experimental settings should also extend the knowledge about the underlying mechanisms of the antihypoxidotic actions. EGB as well as its non-flavone fraction considerably prolonged the survival time of mice under lethal hypoxia. EGB retarded the breakdown of brain energy metabolism in the hypoxic artificially ventilated rat. A corresponding effect was exerted by the non-flavone fraction while the flavone fraction even worsened the metabolic state. The non-flavone fraction increased LCBF in the majority of 35 examined brain regions; a similar effect could be seen after EGB-treatment, while the flavone fraction caused only minor alterations of LCBF. We conclude that the non-flavone fraction of EGB carries the antihypoxidotic activity. Metabolic effects are suggested to cause this activity. Further studies are necessary to elucidate the effective compound within this fraction.