Neuroprotective Effects Of Bilobalide Are Accompanied By A Reduction Of Ischemia-induced Glutamate Release In Vivo
brain-injury; cerebral-artery occlusion; extract egb-761; Ginkgo biloba; Ginkgo biloba; Glucose; inhibition; mice; Microdialysis; Microdialysis; Middle cerebral artery occlusion; Neurosciences & Neurology; phospholipid breakdown; sensorimotor; stroke; stroke
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. (C) 2011 Elsevier B.V. All rights reserved.
Lang D; Kiewert C; Mdzinarishvili A; Schwarzkopf T M; Sumbria R; Hartmann J; Klein J
Brain Research
2011
2011-11
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.brainres.2011.10.005" target="_blank" rel="noreferrer noopener">10.1016/j.brainres.2011.10.005</a>
Metabolic And Transmitter Changes In Core And Penumbra After Middle Cerebral Artery Occlusion In Mice
acetylcholine; Choline; focal ischemia; Glucose; glutamate; glutamate; Glycerol; hippocampus; hippocampus; intracerebral microdialysis; Microdialysis; mutant mice; neurodegenerative disorders; Neurosciences & Neurology; rat; release; reperfusion; Striatum; stroke
Middle cerebral artery occlusion (MCAO) is a popular model in experimental stroke research and causes prominent ischemic damage in the forebrain. To characterize metabolic changes induced by MCAO, we have induced permanent MCAO in mice that were implanted with a microdialysis probe in either striatum or hippocampus. Immediately after the onset of ischemia, glucose levels dropped to <10% of basal values in the striatum while they dropped to 50%, and recovered thereafter, in hippocampus. Extracellular levels of glutamate rose 80-fold in the striatum but only 10-fold, and in a transient fashion, in hippocampus. In striatum, release of acetylcholine briefly increased, then dropped to very low values. Both glycerol and choline levels increased strongly during ischemia in the striatum reflecting membrane breakdown. In hippocampus, glycerol increased transiently while the increase of choline levels was moderate. Taken together, these observations delineate metabolic changes in ischemic mouse brain with the striatum representing the core area of ischemia. In comparison, the dorsal hippocampus was identified as a brain area suitable for monitoring metabolic responses in the penumbra region. (C) 2009 Elsevier B.V. All rights reserved.
Kiewert C; Mdzinarishvili A; Hartmann J; Bickel U; Klein J
Brain Research
2010
2010-02
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.brainres.2009.11.068" target="_blank" rel="noreferrer noopener">10.1016/j.brainres.2009.11.068</a>