Attenuation of ischemia-induced rat brain injury by 2-(-2-benzofuranyl)-2-imidazoline, a high selectivity ligand for imidazoline I2 receptors

Abstract

Objective: The aim of this study was to determine whether 2-(2-benzofuranyl)-2-imidazoline, an imidazoline I2 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.