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Abstract

Grant Number:	1R41NS053041-01A1
Project Title:	Retinoids as Novel Treatment of Ischemic Stroke

PI Information:	Name	Email	Title
	ROULLET, JEAN-BAPTISTE O.	roulletj@ohsu.edu

Abstract: DESCRIPTION (provided by applicant): Stroke is the third leading cause of death in the U.S. and a major source of disability. Ischemic stroke, the most common type, is associated with a dramatic increase in calcium influx in brain tissue, an increased production in reactive oxygen species (ROS), cell death and inflammation. Studies by the PI have shown that retinoids block neuronal voltage-gated calcium channels. Studies by others suggest that retinoids reduce tissue levels of reactive oxygen species and prevents cellular apoptosis, increase tissue plasminogen activator, favorably modify the balance of pro-inflammatory and inflammatory cytokines and attenuate inflammation in vivo. Together, the data suggest that retinoids might be neuroprotective and potentially useful in the treatment of ischemic stroke. Our goal is to demonstrate that retinoids have neuroprotective activity in vivo. Specifically, we propose to demonstrate that treatment with retinoids: 1) attenuates post-stroke motor deficits using a mouse model of permanent focal cerebral ischemia (middle cerebral artery occlusion), 2) reduces cerebral infarct size, and 3) reduces the expression of the biochemical markers of apoptosis, ROS production and inflammation in the ischemic brain. The project will provide a rationale for the development of retinoid-based formulations to treat ischemic stroke and for the screening of retinoid libraries in search of more potent compounds.

Thesaurus Terms:

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Institution:	ACRYMED, INC.
	9560 SW Nimbus Ave.
	BEAVERTON, OR 97008
Fiscal Year:	2006
Department:
Project Start:	15-SEP-2006
Project End:	31-AUG-2008
ICD:	NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
IRG:	ZRG1

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