Ginkgolide B On Central Neuronal Discharge Activity In Anesthetized Rats

Background: Ginkgolide B is one of the major constituents of the terpenoid fraction of Ginkgo biloba extract (GbE). Previous investigations suggested that ginkgolide B is a potent platelet-activating factor receptor antagonist, which is also regarded as having neuroprotective effects in the CNS. Recent evidence suggests that GbE protects against neuronal death in global brain ischemia and in glutamate-induced excitotoxicity. The mechanisms underlying ginkgolide B's beneficial effects on central neurons activity still need to be clarified as yet and the effect of ginkgolide B on spontaneous discharge of hippocampal neurons has not been reported.Aim: To examine the effects of Ginkgolide B (BN52021) on the discharges of neurons in CA1 area of hippocampal slices.Methods: Using extracellular recording technique.Results: (1) In response to the application of ginkgolide B (0.1, 1, 10μmol/L; n=43) into the perfusate for 2 min, the spontaneous discharge rates (SDR) of 42/43 (97.67%) neurons were significantly decreased in a dose-dependent manner. (2) Pretreatment with L-glutamate (L-Glu, 0.2mmol/L) led to a marked increase in the SDR of all 10 (100%) neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B (1μmol/L) was applied into the perfusate for 2 min. (3) In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 (0.1μmol/L), induced a significant increase in the discharge rate of 8/8 (100%) neurons. Ginkgolide B (1μmol/L) applied into the perfusate inhibited the discharges of 7/8 (87.5%) slices. (4) In 8 neurons, the broad potassium channels blocker, tetraethylammonium (TEA, 1mmol/L) completely blocked the inhibitory effect of ginkgolide B (1μmol/L).Conclusion: These results suggest that ginkgolide B can inhibit the electrical activity of CA1 neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and may be concerned with delayed rectifier potassium channel (KDR),which indicated that ginkgolide B play a protective role on the central neurons. Background: Ginkgolide B is one of the major constituents of the terpenoid fraction of Ginkgo biloba extract (GbE). Previous investigations suggested that ginkgolide B is a potent platelet-activating factor receptor antagonist, which is also regarded as having protective effects in cardiovascular system and CNS. Recent evidence suggests that GbE protects against neuronal death in global brain ischemia and in glutamate-induced excitotoxicity. The mechanisms underlying ginkgolide B's beneficial effects on central neurons activity still need to be clarified as yet.Aim: To study the central role of Ginkgolide B (BN52021) in regulating cardiovascular function of nervous center by examining the effects of GST on the electrical activity of rat paraventricular nucleus (PVN) neurons in hypothalamic slice preparation and to elucidate the mechanism involved.Methods: Using extracellular single-unit discharge recording technique.Results: (1) In response to the application of ginkgolide B (0.1, 1, 10μmol/L; n=27) into the perfusate for 2 min, the spontaneous discharge rates (SDR) of 26/27 (96.30%) neurons were significantly decreased in a dose-dependent manner. (2) Pretreatment with L-glutamate (L-Glu, 0.2mmol/L) led to a marked increase in the SDR of all 8 (100%) neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B (1μmol/L) was applied into the perfusate for 2 min. (3) In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 (0.1μmol/L), induced a significant increase in the discharge rate of 8/8 (100%) neurons. Ginkgolide B (1μmol/L) applied into the perfusate inhibited the discharges of 8/8 (100%) slices. (4) In 8 neurons, the broad potassium channels blocker, tetraethylammonium (TEA, 1mmol/L) completely blocked the inhibitory effect of ginkgolide B (1μmol/L).Conclusion: These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and may be concerned with delayed rectifier potassium channel (KDR).