Src family kinase-inhibitor PP2 reduces focal ischemic brain injury
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
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.
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
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-72448DOI: 10.1111/j.1600-0404.2004.00306.xPubMedID: 15285775OAI: oai:DiVA.org:uu-72448DiVA: diva2:100359