Src family kinase-inhibitor PP2 reduces focal ischemic brain injury

• 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.

Nyckelord

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

MEDICINE

MEDICIN

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)