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


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).


CONCLUSIONS
PP2 is a potential neuroprotective agent in cerebral ischemia-reperfusion. The interference of PP2 with SFKs and/or other pathways remains to be elucidated.
Department of Surgical Sciences, Anesthesiology and Intensive Care, Uppsala University Hospital, Uppsala, Sweden. Fredrik.Lennmyr@surgsci.uu.se
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F
Lennmyr
A
A
Ericsson
P
P
Gerwins
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S
Akterin
H
H
Ahlström
A
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Terént
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013778:Tetrazolium Salts; D016896:Treatment Outcome; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
C412373:AG 1879; D018696:Neuroprotective Agents; D011743:Pyrimidines; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; D019061:src-Family Kinases