Stroke is the third leading cause of death in the United States and the primary cause of neurologic morbidity. Vascular causes of dementia are the second most common cause of dementia in elderly Americans. No specific therapy currently exists for either stroke or cerebral vascular dementia. The failure to develop effective therapy for these diseases may be partially the result of the absence of a reproducible animal model of this type of cerebral vascular disease. Recently, we have developed new animal models that allow for the rapid and inexpensive testing of new drugs that may be effective in the treatment of cerebral vascular disease. We propose to extend our previous observations by refining a method for the quantitative analysis of the histopathologic consequences of multifocal cerebral ischemia. We will use the quantitative methods to assess the effect of drug treatment on histopathologic consequences of cerebral ischemia. Finally, we propose to quantify the effect of multifocal cerebral ischemia on behavior (learning). We hypothesize that learning behavior will change in a measurable way depending on the topographic distributions of lesions following ischemia and that these observations will be altered by pharmacologic therapy. These methods will allow us to screen new drugs for their potential benefit in the treatment of victims of stroke or vascular dementia, and will provide insights into the mechanisms underlying the dementia apparent in many patients with vascular lesions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29NS026783-04
Application #
3477585
Study Section
Neurology A Study Section (NEUA)
Project Start
1989-08-01
Project End
1994-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Lyden, P D; Lonzo, L (1994) Combination therapy protects ischemic brain in rats. A glutamate antagonist plus a gamma-aminobutyric acid agonist. Stroke 25:189-96
Lyden, P D; Zweifler, R; Mahdavi, Z et al. (1994) A rapid, reliable, and valid method for measuring infarct and brain compartment volumes from computed tomographic scans. Stroke 25:2421-8
Lyden, P D; Hedges, B (1992) Protective effect of synaptic inhibition during cerebral ischemia in rats and rabbits. Stroke 23:1463-9;discussion 1469-70
Lyden, P D; Zivin, J A; Chabolla, D R et al. (1992) Quantitative effects of cerebral infarction on spatial learning in rats. Exp Neurol 116:122-32
Lyden, P D; Lau, G T (1991) A critical appraisal of stroke evaluation and rating scales. Stroke 22:1345-52