title: Pharmacological investigations on possible role of Src kinases in neuroprotective mechanism of ischemic postconditioning in mice.
abstract: The present study has been undertaken to investigate the possible role of Src Kinases in a neuroprotective mechanism of ischemic postconditioning in mice. Bilateral carotid artery occlusion for 12 min followed by reperfusion for 24 h produced a significant increase in cerebral infarct size and neurological severity score along with impairment of memory and motor coordination. Ischemic postconditioning involving three episodes of 10 s carotid artery occlusion with intermittent reperfusion of 10 s proceeding ischemic insult of 12 min, produced a significant decrease in cerebral infarct size and neurological severity score along with reversal of ischemia-reperfusion induced impairment of memory and motor coordination. Ischemic postconditioning induced neuroprotective effects were significantly attenuated by pre-treatment of selective Src Kinase inhibitors SU-6656 (4 mg/kg i.p.) and PP1 (0.2 mg/kg i.p.). It may be concluded that the neuroprotective effect of ischemic postconditioning probably involves activation of Src Kinase pathway.
authors.affiliation: Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University , Patiala, Punjab , India.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.forename: Amteshwar S
authors.initials: AS
authors.lastname: Jaggi
authors.forename: Nirmal
authors.initials: N
authors.lastname: Singh
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications* / Q000209:etiology; D002544:Cerebral Infarction / Q000209:etiology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D057775:Ischemic Postconditioning; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D045442:Rotarod Performance Test; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; D007211:Indoles; D018696:Neuroprotective Agents; D011720:Pyrazoles; D011743:Pyrimidines; C416927:SU 6656; D013449:Sulfonamides; D019061:src-Family Kinases
keywords: Ischemic postconditioning; Src kinase; cerebral ischemia; neuroprotection