PAF Antagonist Ginkgolide B Reduces Postischemic Neuronal Damage in Rat Brain Hippocampus

Oberpichler, H.; Sauer, Dirk; Rossberg, C; Hd, Mennel; Krieglstein, Josef

doi:10.1038/jcbfm.1990.17

Cited by 123 publications

(45 citation statements)

References 7 publications

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“…Preischemic administration of ginkgolide B (50 mg/kg) was found to significantly reduce neuronal necrosis at 7 days in a transient forebrain ischemia model in rats. 27 In the same model, Krieglstein et al 28 found that EGb (100/kg IV) given 45 minutes after ischemia was able to increase cerebral blood flow and diminish delayed hypoperfusion. EGb also produced beneficial effects on functional outcome in a cerebral microemboli model in rats 29 and in a global cerebral ischemia model in dogs.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Antioxidant Therapies in Transient Focal Ischemia in Mice

Clark

Rinker

Lessov

et al. 2001

Stroke

127

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Background and Purpose-Ginkgo biloba extract (EGb) and ␣-lipoic acid (LA) are commercially available "antioxidant supplements" with a variety of actions that may be beneficial during acute stroke. These actions include inhibiting platelet and leukocyte activation and adhesion, reducing free radical generation, and increasing cerebral blood flow. Both EGb and LA have been shown to be neuroprotective in cell culture and global central nervous system ischemia models. In this study we investigated the neuroprotective efficacy of EGb and LA in a clinically relevant, transient focal central nervous system ischemic model. Methods-In the EGb study, 60 adult C57blk mice were randomized to treatment with EGb given orally (via gavage) for 7 days: low dose, 50 EGb mg/kg daily; high dose, 100 mg/kg daily; matched placebo. On day 7, reversible middle cerebral artery occlusion was produced by advancing a silicone-coated 8-0 filament into the internal carotid artery for 45 minutes followed by reperfusion. At 24 hours, the animals were evaluated on a 28-point clinical scale, and infarct volume was determined with the use of triphenyltetrazolium chloride. In the LA study, 24 C57blk mice were treated with 100 mg/kg SC of LA or placebo 1.5 hours before transient MCAO, as in the EGb study.

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Section: Discussionmentioning

confidence: 99%

Efficacy of Antioxidant Therapies in Transient Focal Ischemia in Mice

Clark

Rinker

Lessov

et al. 2001

Stroke

127

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“…EGb 761 also has anti-inflammatory effects and protective actions against brain damage through its terpenes and ginkgolides. 37,38 The ginkgolide B acts as an antagonist of PAF, 37 a factor that induces proinflammatory effects 39 and is activated in the HIV-infected brain. 40 Besides the free radical theory, inflammation is noted in the brains of HIV-infected individuals and of Tat transgenic mice.…”

Section: Neurotherapeutic Function Of Egb 761 Against Tat Neurotoxicitymentioning

confidence: 99%

Protection against Human Immunodeficiency Virus Type 1 Tat Neurotoxicity by Ginkgo biloba Extract EGb 761 Involving Glial Fibrillary Acidic Protein

Zou

Kim

Zhou

et al. 2007

The American Journal of Pathology

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Human immunodeficiency virus (HIV)-1 Tat protein isan important pathogenic factor in HIV-associated neuropathogenesis. Despite recent progress, the molecular mechanisms underlying Tat neurotoxicity are still not completely understood. However, few therapeutics have been developed to specifically target HIV infection in the brain. Recent development of an inducible brain-specific Tat transgenic mouse model has made it possible to define the mechanisms of Tat neurotoxicity and evaluate anti-neuroAIDS therapeutic candidates in the context of a whole organism. Herein, we demonstrate that administration of EGb 761, a standardized formulation of Ginkgo biloba extract, markedly protected Tat transgenic mice from Tat-induced developmental retardation, inflammation, death, astrocytosis, and neuron loss. EGb 761 directly down-regulated glial fibrillary acidic protein (GFAP) expression at both protein and mRNA levels. This down-regulation was, at least in part, attributable to direct effects of EGb 761 on the interactions of the AP1 and NF-B transcription factors with the GFAP promoter. Most strikingly, Tat-induced neuropathological phenotypes including macrophage/microglia activation, central nervous system infiltration of T lymphocytes, and oxidative stress were significantly alleviated in GFAP-null/Tat transgenic mice. Taken together, these results provide the first evidence to support the potential for clinical use of EGb 761 to treat HIV-associated neurological diseases. Moreover, these findings suggest for the first time that GFAP activation is directly involved in Tat neurotoxicity, supporting the notion that astrocyte activation or astrocytosis may directly contribute to HIV-associated neurological disorders.

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“…Many of these actions have been studied in nonneural cells and are assumed to occur in the nervous system as well. Therefore, excessive PAF promotes neuronal damage, and PAFreceptor antagonists elicit neuroprotection in various models of neural injury (120,(133)(134)(135)(136)(137).…”

Section: Paf-mediated Cell Signal Transduction In the Nervous Systemmentioning

confidence: 99%

Synaptic lipid signaling

Bazán

2003

Journal of Lipid Research

231

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Neuronal cellular and intracellular membranes are rich in specialized phospholipids that are reservoirs of lipid messengers released by specific phospholipases and stimulated by neurotransmitters, neurotrophic factors, cytokines, membrane depolarization, ion channel activation, etc. Secretory phospholipases A 2 may be both intercellular messengers and generators of lipid messengers. The highly networked nervous system includes cells (e.g., astrocytes, oligodendrocytes, microglial cells, endothelial microvascular cells) that extensively interact with neurons; several lipid messengers participate in these interactions. This review highlights modulation of postsynaptic membrane excitability and long-term synaptic plasticity by cyclooxygenase-2-generated prostaglandin E2, arachidonoyldiacylcylglycerol, and arachidonic acid-containing endocannabinoids. The peroxidation of docosahexaenoic acid (DHA), a critical component of excitable membranes in brain and retina, is promoted by oxidative stress. DHA is also the precursor of enzyme-derived, neuroprotective docosanoids. The phospholipid platelet-activating factor is a retrograde messenger of long-term potentiation, a modulator of glutamate release, and an upregulator of memory formation. Lipid messengers modulate signaling cascades and contribute to cellular differentiation, function, protection, and repair in the nervous system. Lipidomic neurobiology will advance our knowledge of the brain, spinal cord, retina, and peripheral nerve function and diseases that affect them, and new discoveries on networks of signaling in health and disease will likely lead to novel therapeutic interventions. -Bazan, N. G. Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor. J. Lipid Res.

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PAF Antagonist Ginkgolide B Reduces Postischemic Neuronal Damage in Rat Brain Hippocampus

Abstract: Summary:We investigated the effect of the known an tagonist 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 IO-min forebrain ischemia. Preischemic application of

Cited by 123 publications

References 7 publications

Efficacy of Antioxidant Therapies in Transient Focal Ischemia in Mice

Efficacy of Antioxidant Therapies in Transient Focal Ischemia in Mice

Protection against Human Immunodeficiency Virus Type 1 Tat Neurotoxicity by Ginkgo biloba Extract EGb 761 Involving Glial Fibrillary Acidic Protein

Synaptic lipid signaling

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