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


CONCLUSIONS
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.
Han
Zhao
Z
Division of Stroke Medicine, First Affiliate Hospital of Wenzhou Medical College, Wenzhou 325000, China. wzhanzhao@yahoo.cn
Xiao
Mei-Juan
MJ
Shao
Bei
B
Zheng
Rong-Yuan
RY
Yang
Guo-Yuan
GY
Jin
Kunlin
K
D000818:Animals; D001572:Benzofurans / Q000627:therapeutic use*; D001930:Brain Injuries / Q000517:prevention & control*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D019329:Idazoxan / Q000627:therapeutic use; D007093:Imidazoles / Q000627:therapeutic use*; D054755:Imidazoline Receptors; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D009460:Neurologic Examination / Q000379:methods; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts
D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; C487767:imidazoline receptor 2; C103723:2-(2-benzofuranyl)-2-imidazoline; C009591:triphenyltetrazolium; D053148:Caspase 3; D019329:Idazoxan