Published Online
on May 8, 2003

A more recent version of this article appeared on June 1, 2003

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Submitted on December 30, 2002
Accepted on December 30, 2002

Fibroblast Growth Factor-18 Reduced Infarct Volumes and Behavioral Deficits After Transient Occlusion of the Middle Cerebral Artery in Rats

Jeff L. Ellsworth PhD^*; Richard Garcia BS; Jin Yu MD; and Mark S. Kindy PhD

From ZymoGenetics, Inc, Seattle, Wash (J.L.E., R.G.); Department of Physiology and Neuroscience, Stroke Program and Center on Aging, Medical University of South Carolina, and Ralph H. Johnson, Veterans Affairs Medical Center, Charleston (J.Y., M.S.K.); and Molecular Therapeutics, Inc, Mt Pleasant, SC (M.S.K.).

^* To whom correspondence should be addressed. E-mail: jefe{at}zgi.com.

Background and Purpose--Fibroblast growth factor 18 (FGF18) is expressed in rodent brain and is a trophic factor for neuron-derived cells in culture. The purpose of the present study was to evaluate whether FGF18 was neuroprotective in a rat model of cerebral ischemia and to compare the results with those obtained with FGF2.

Methods--Cerebral ischemia was produced in rats by a transient 2-hour occlusion of the middle cerebral artery (MCAo) with an intraluminal filament followed by 22-hour reperfusion. Starting 15 minutes after MCAo, FGF18 or FGF2 was administered by a 3-hour intravenous infusion. Infarct volumes and behavioral deficits were measured 24 hours after MCAo.

Results--Infusion of FGF18 produced dose-dependent reductions in infarct volumes and improvements in tests of reference and working memory, motor ability, and exploratory behavior. FGF18 was more efficacious than FGF2 on virtually all measures examined. The reductions in infarct volume and behavioral deficit were associated with FGF-mediated increases in regional cerebral blood flow.

Conclusions--These results demonstrate that FGF18 is an effective neuroprotective agent in a rat model of transient MCAo.

Key words: animal models • growth factors • neuroprotection • rats

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