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Src family kinase-inhibitor PP2 reduces focal ischemic brain injury.

AbstractOBJECTIVES:
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.
AuthorsF Lennmyr, A Ericsson, P Gerwins, S Akterin, H Ahlström, A Terént
JournalActa neurologica Scandinavica (Acta Neurol Scand) Vol. 110 Issue 3 Pg. 175-9 (Sep 2004) ISSN: 0001-6314 [Print] Denmark
PMID15285775 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • AG 1879
  • Neuroprotective Agents
  • Pyrimidines
  • Tetrazolium Salts
  • triphenyltetrazolium
  • src-Family Kinases
Topics
  • 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)
  • Tetrazolium Salts
  • Treatment Outcome
  • src-Family Kinases (antagonists & inhibitors, metabolism)

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