Abstract

With the exception of aspirin in stroke prevention, no other therapeutic modalities have been proven to be efficacious in reducing ischemia-related brain damage or death using rigorously designed therapeutic protocols. Recent advances in the understanding of pathophysiology in cerebrovascular disease have generated enthusiasm in trials of new drugs. Clinical trials to confirm the therapeutic efficacy of new drugs in human stroke are costly, difficult to achieve and may involve risks for stroke victims. Preclinical trial using reliable animal models are desirable to preclude less promising drugs from entering the clinical trials. A focal ischemia model in the rat allowing objective and quantitative determination of infarct volume which varies with duration of ischemic insult will be established as an animal therapeutic model for ischemic stroke. Therapeutic protocol comparable to that of human trials will be applied to selected new drugs to determine their therapeutic efficacy. The overall objectives of this project are to establish a pharmacologically sound procedure to identify effective new drugs for future human trials in an economic and timely fashion.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS025545-02
Application #
3410799
Study Section
Neurology A Study Section (NEUA)
Project Start
1988-04-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Baylor College of Medicine
Department
Type
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Chen, Shang-Der; Lee, Jin-Moo; Yang, Ding-I et al. (2002) Combination therapy for ischemic stroke: potential of neuroprotectants plus thrombolytics. Am J Cardiovasc Drugs 2:303-13
Xu, J; Chen, S; Ahmed, S H et al. (2001) Amyloid-beta peptides are cytotoxic to oligodendrocytes. J Neurosci 21:RC118
Xu, J; Chen, S; Ku, G et al. (2001) Amyloid beta peptide-induced cerebral endothelial cell death involves mitochondrial dysfunction and caspase activation. J Cereb Blood Flow Metab 21:702-10
Chen, H; Hu, C J; He, Y Y et al. (2001) Reduction and restoration of mitochondrial dna content after focal cerebral ischemia/reperfusion. Stroke 32:2382-7
Kanellopoulos, G K; Xu, X M; Hsu, C Y et al. (2000) White matter injury in spinal cord ischemia: protection by AMPA/kainate glutamate receptor antagonism. Stroke 31:1945-52
Majid, A; He, Y Y; Gidday, J M et al. (2000) Differences in vulnerability to permanent focal cerebral ischemia among 3 common mouse strains. Stroke 31:2707-14
Ahmed, S H; He, Y Y; Nassief, A et al. (2000) Effects of lipopolysaccharide priming on acute ischemic brain injury. Stroke 31:193-9
Xu, J; He, L; Ahmed, S H et al. (2000) Oxygen-glucose deprivation induces inducible nitric oxide synthase and nitrotyrosine expression in cerebral endothelial cells. Stroke 31:1744-51
Ahmed, S H; Shaikh, A Y; Shaikh, Z et al. (2000) What animal models have taught us about the treatment of acute stroke and brain protection. Curr Atheroscler Rep 2:167-80
Chao, K S; Hsu, J S; Xu, J et al. (1999) Differential effect of cycloheximide on neuronal and glioma cells treated with chemotherapy and radiation. J Neurooncol 45:19-26

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