Research ReportNeuroprotective effects of bilobalide are accompanied by a reduction of ischemia-induced glutamate release in vivo

Neuroprotective properties of bilobalide, a specific constituent of Ginkgo extracts, were tested in a mouse model of stroke. After 24 h of middle cerebral artery occlusion (MCAO), bilobalide reduced infarct areas in the core region (striatum) by 40-50% when given at 10 mg/kg 1 h prior to MCAO. Neuroprotection was also observed at lower doses, or when the drug was given 1 h past stroke induction. Sensorimotor function in mice was improved by bilobalide as shown by corner and chimney tests. When brain metabolism in situ was monitored by microdialysis, MCAO caused a rapid disappearance of extracellular glucose in the striatum which returned to baseline levels after reperfusion. Extracellular levels of glutamate were increased by more than ten-fold in striatal tissue, and by four- to fivefold in hippocampal tissue (penumbra). Bilobalide did not affect glucose levels but strongly attenuated glutamate release in both core and penumbra regions. Bilobalide was equally active when given locally via the microdialysis probe and also reduced ischemia-induced glutamate release in vitro in brain slices. We conclude that bilobalide is a strong neuroprotectant in vivo at doses that can be used therapeutically in humans. The mechanism of action evidently involves reduction of glutamate release, thereby reducing excitotoxicity.

► Bilobalide is a neuroprotective compound present in Ginkgo biloba extracts. ► Pure bilobalide (1-10 mg/kg) reduces neuronal cell death after brain ischemia. ► Bilobalide appears to act locally in the infarcted brain. ► The mechanism of action involves reduction of ischemia-induced glutamate release.