Attenuation of ischemia-induced rat brain injury by 2-(-2-benzofuranyl)-2-imidazoline, a high selectivity ligand for imidazoline I(2) receptors

Neurol Res. 2009 May;31(4):390-5. doi: 10.1179/174313209X444116.

Abstract

Objective: The aim of this study was to determine whether 2-(2-benzofuranyl)-2-imidazoline, an imidazoline I(2) receptor ligand, could protect against cell death from brain injury and improve the functional outcome after focal cerebral ischemia in rats.

Methods: Transient focal ischemia was induced by suture occlusion of the middle cerebral artery. Rats were intraperitoneally treated with a vehicle, 2-(2-benzofuranyl)-2-imidazoline or idazoxan immediately after focal ischemia. Infarct volume was assessed by 2,3,5-triphenyltrazolium chloride staining and neurobehavioral deficits were monitored. The volume of cell death in the penumbra after ischemia was determined by immunostaining using anti-cleaved caspase-3 antibody and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL).

Results: Both 2-(2-benzofuranyl)-2-imidazoline and idazoxan significantly improved the neurological score compared with the vehicle at 24 hours after focal ischemia. Treatment with 2-(2-benzofuranyl)-2-imidazoline or idazoxan also significantly reduced infarct volume and the number of both caspase-3- and TUNEL-positive cells in the penumbra compared with vehicle-treated rats (p<0.01 and p<0.05, respectively).

Conclusion: The results suggest the neuroprotective role of 2-(2-benzofuranyl)-2-imidazoline and idazoxan in focal cerebral ischemia, and may therefore represent useful targets for developing new treatments for stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzofurans / therapeutic use*
  • Brain Injuries / prevention & control*
  • Brain Ischemia / complications
  • Brain Ischemia / drug therapy*
  • Caspase 3 / metabolism
  • Disease Models, Animal
  • Idazoxan / therapeutic use
  • Imidazoles / therapeutic use*
  • Imidazoline Receptors
  • In Situ Nick-End Labeling / methods
  • Male
  • Neurologic Examination / methods
  • Neuroprotective Agents / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Tetrazolium Salts

Substances

  • Benzofurans
  • Imidazoles
  • Imidazoline Receptors
  • Neuroprotective Agents
  • Tetrazolium Salts
  • imidazoline receptor 2
  • 2-(2-benzofuranyl)-2-imidazoline
  • triphenyltetrazolium
  • Caspase 3
  • Idazoxan