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Src family kinase-inhibitor PP2 reduces focal ischemic brain injury
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. (Anaesthesiology and Intensive Care)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology. (Nyman)
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2004 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 110, no 3, 175-9 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To investigate the neuroprotective potential of the Src family kinase (SFK) inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo(3,4-d)pyrimidine (PP2) in transient focal cerebral ischemia in the rat. MATERIAL AND METHODS: Sprague-Dawley rats were exposed to transient (90 min) middle cerebral artery occlusion (MCAO) and evaluated after 1 day of survival. PP2 (1.5 mg/kg i.p.) or vehicle was given 30 min after MCAO. The lesions were examined with magnetic resonance imaging (MRI), tri-phenyl tetrazolium chloride (TTC) staining and the functional outcome was determined using neurological scoring according to Bederson et al. RESULTS: PP2-treated rats showed approximately 50% reduction of infarct size on T2-weighted MRI and in TTC staining compared with controls (P < 0.05). Moreover, the neurological score was better in the PP2 group than controls (P < 0.05). CONCLUSION: PP2 is a potential neuroprotective agent in cerebral ischemia-reperfusion. The interference of PP2 with SFKs and/or other pathways remains to be elucidated.

Place, publisher, year, edition, pages
2004. Vol. 110, no 3, 175-9 p.
Keyword [en]
Animals, Brain/*drug effects/enzymology/physiopathology, Brain Ischemia/*drug therapy/enzymology/physiopathology, Cerebral Infarction/drug therapy/enzymology/pathology, Disease Models; Animal, Infarction; Middle Cerebral Artery/*drug therapy/enzymology/physiopathology, Magnetic Resonance Imaging, Male, Neuroprotective Agents/*pharmacology/therapeutic use, Pyrimidines/*pharmacology/therapeutic use, Rats, Rats; Sprague-Dawley, Recovery of Function/drug effects/physiology, Research Support; Non-U.S. Gov't, Tetrazolium Salts, Treatment Outcome, src-Family Kinases/*antagonists & inhibitors/metabolism
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-72448DOI: 10.1111/j.1600-0404.2004.00306.xPubMedID: 15285775OAI: oai:DiVA.org:uu-72448DiVA: diva2:100359
Available from: 2005-08-16 Created: 2005-08-16 Last updated: 2011-05-05Bibliographically approved

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Lennmyr, FredrikGerwins, PärAhlström, HåkanTerént, Andreas
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Department of Surgical SciencesDepartment of Genetics and PathologyRadiologyDepartment of Medical Sciences
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