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Administration of the p38 MAPK inhibitor SB203580 affords brain protection with a wide therapeutic window against focal ischemic insult
- Source :
- Journal of neuroscience research. 73(4)
- Publication Year :
- 2003
-
Abstract
- We have reported previously the delayed and differential induction of p38alpha and p38beta mitogen-activated protein kinases (MAPKs) in microglia and astrocytes, respectively, in brain after transient global ischemia. We report here the sustained induction and activation of p38alpha MAPK in activating microglia in rat brain after transient middle cerebral artery occlusion (MCAO). The intraventricular administration of SB203580, a p38 MAPK inhibitor, 30 min before MCAO reduced the infarct volume to 50% of the control, which was accompanied by the significant improvement of neurological deficits. More interestingly, the infarct volume was reduced to 72% and 77% when SB203580 was administered 6 hr and 12 hr after MCAO, respectively. The induction of various factors involved in inflammatory processes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and cyclooxygenase-2 (COX-2), was suppressed by the administration of SB203580 at 6 hr after MCAO. These results suggest that sustained activation of p38 MAPK pathway and p38 MAPK-associated inflammatory processes play a crucial role in postischemic brain.
- Subjects :
- MAPK/ERK pathway
Male
Time Factors
Pyridines
Nitric Oxide Synthase Type II
Tetrazolium Salts
Pharmacology
Mitogen-Activated Protein Kinase 14
Rats, Sprague-Dawley
Lectins
Medicine
Neurologic Examination
Microglia
biology
Kinase
Reverse Transcriptase Polymerase Chain Reaction
Anti-Inflammatory Agents, Non-Steroidal
Imidazoles
Brain
Infarction, Middle Cerebral Artery
Immunohistochemistry
Nitric oxide synthase
Isoenzymes
medicine.anatomical_structure
Anesthesia
cardiovascular system
Cytokines
Tumor necrosis factor alpha
Mitogen-Activated Protein Kinases
Brain Infarction
p38 mitogen-activated protein kinases
Blotting, Western
Ischemia
Neuroprotection
Cellular and Molecular Neuroscience
Animals
cardiovascular diseases
RNA, Messenger
business.industry
medicine.disease
Rats
Disease Models, Animal
Gene Expression Regulation
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
Astrocytes
biology.protein
Nitric Oxide Synthase
business
Subjects
Details
- ISSN :
- 03604012
- Volume :
- 73
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Journal of neuroscience research
- Accession number :
- edsair.doi.dedup.....58b0be449a7b9e8a764ee29521de63cb