POSTER PRESENTATION ABSTRACTS
Please note: All posters will be displayed in
Salons 10-12.
FRIDAY, 5:45-6:30 PM
Saleem S, Doré, S*.
Reduction of infarct size by Ginkgo biloba (EGb-761).
Johns Hopkins University, SOM, ACCM Dept sdore@jhmi.edu
*Presenting author
PURPOSE: The standardized extract of Ginkgo
biloba (EGb 761) has been widely employed for its significant benefit
in neurodegenerative disorders. Although antioxidative actions have
been attributed to this extract, the mechanisms of the multiple principles
involved in this pharmacologic activity are not completely established.
Ischemic stroke and Alzheimer diseases are frequently associated with
oxidative stress and defects in the cellular protective mechanisms.
Oxidative stress, which has been implicated in the pathogenesis of ischemic
brain injury, degrades heme proteins, such as cytochrome P450, and causes
elevation in the level of cellular free heme, which can catalyze the
formation of reactive oxygen species. Heme oxygenase (HO) is the rate-limiting
enzyme in the catabolism of heme, followed by production of biliverdin,
free iron, and carbon monoxide (CO). We tested the hypothesis that EGb
761 would afford neuronal protection by inducing the endogenous antioxidant
enzyme, heme oxygenase. We and others have reported that modulation
of HO activity could have direct beneficial consequences in cerebral
ischemia. By using a mouse middle cerebral artery occlusion model, we
investigated the possible role of EGb 761 on neurobehavioral activity
and infarct volume in male wildtype (WT) and HO knockout (HO-/-) mice.
METHODS: The right MCA was occluded for 2 h
using intraluminal 8-0 silicon monofilament, and reperfusion was allowed
for 22 h. Neurologic deficit was evaluated and infarct volume was quantified.
RESULTS: The neurobehavioral activity decreased, while infarct size
increased significantly (p<0.05) in WT mice. All of the alternations
induced by ischemia were significantly (p<0.01) attenuated by 7-day
pretreatment with EGb 761 (100 mg/kg b.w. p.o.) and correlated well
with TTC infarct volume measurement by decreasing the infarct size following
MCA occlusion and reperfusion in WT mice.
CONCLUSION: This study suggests that the protective
effects of Ginkgo biloba in focal cerebral ischemia could be mediated
through beneficial actions of heme degradation and its metabolites.
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