Pharmacological investigations on possible role of Src kinases in neuroprotective mechanism of ischemic postconditioning in mice

Int J Neurosci. 2014 Oct;124(10):777-86. doi: 10.3109/00207454.2013.879869. Epub 2014 Feb 6.

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.

Keywords: Ischemic postconditioning; Src kinase; cerebral ischemia; neuroprotection.

MeSH terms

  • Animals
  • Brain Ischemia / complications*
  • Brain Ischemia / etiology
  • Cerebral Infarction / etiology*
  • Cerebral Infarction / prevention & control*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Ischemic Postconditioning*
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / drug therapy
  • Memory Disorders / etiology
  • Mice
  • Motor Activity / drug effects
  • Muscle Strength / drug effects
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use*
  • Pyrazoles / therapeutic use
  • Pyrimidines / therapeutic use
  • Rotarod Performance Test
  • Severity of Illness Index
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use
  • Time Factors
  • src-Family Kinases / metabolism*

Substances

  • 4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine
  • Indoles
  • Neuroprotective Agents
  • Pyrazoles
  • Pyrimidines
  • SU 6656
  • Sulfonamides
  • src-Family Kinases