Abstract

The molecular and cellular mechanism of vasogenic edema in ischemic stroke remains to be fully elucidated. Inflammation initiated by ischemic brain injury may contribute to the development of vasogenic brain edema. The major findings in acute inflammation in tissue are: (1) accumulation of inflammatory mediators; (2) infiltration of inflammatory cells (polymorphonuclear cells and platelets); and (3) vascular injury with increased permeability. All these features have been noted in cerebral infarction. The putative mediators of vasogenic brain edema are also inflammatory mediators. We propose to investigate selected aspects of post-ischemic inflammatory reaction in an ischemic stroke model in the rat. The main focus of this proposal will be on the kinin-arachidonic acid cascade. We will characterize the activation of this cascade in relation to the evolution of brain edema, protein extravasation and polymorphonuclear cell infiltration. The roles of cellular and chemical mediators relevant to kinin-arachidonic acid cascade will be studied. The ultimate goal of this proposal is to develop new therapeutic regimens for treatment of ischemic brain edema which remains to be a major cause of death within one week of stroke onset.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS028995-02
Application #
3415702
Study Section
Neurology A Study Section (NEUA)
Project Start
1990-02-01
Project End
1995-01-31
Budget Start
1991-02-01
Budget End
1992-01-31
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

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

  Publications

Lin, Teng-nan; Kim, Gyoeng-Moon; Chen, Jean-Ju et al. (2003) Differential regulation of thrombospondin-1 and thrombospondin-2 after focal cerebral ischemia/reperfusion. Stroke 34:177-86
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
Yin, Ke-jie; Chen, Shang-Der; Lee, Jin-Moo et al. (2002) ATM gene regulates oxygen-glucose deprivation-induced nuclear factor-kappaB DNA-binding activity and downstream apoptotic cascade in mouse cerebrovascular endothelial cells. Stroke 33:2471-7
Yin, J H; Yang, D I; Chou, H et al. (2001) Inducible nitric oxide synthase neutralizes carbamoylating potential of 1,3-bis(2-chloroethyl)-1-nitrosourea in c6 glioma cells. J Pharmacol Exp Ther 297:308-15
Yan, P; Li, Q; Kim, G M et al. (2001) Cellular localization of tumor necrosis factor-alpha following acute spinal cord injury in adult rats. J Neurotrauma 18:563-8
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

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