title: Tropisetron ameliorates ischemic brain injury in an embolic model of stroke.
abstract: Tropisetron is widely used to counteract chemotherapy-induced emesis. Evidence obtained from human and animal studies shows that tropisetron possesses anti-inflammatory properties. In this study, we assessed the effect of tropisetron on brain damage in a rat thromboembolic model of stroke. Stroke was rendered in rats by introduction of an autologous clot into the middle cerebral artery (MCA). Tropisetron (1 or 3mg/kg); m-chlorophenylbiguanide (mCPBG), a selective 5-HT(3) receptor agonist (15 mg/kg); tropisetron (3mg/kg) plus mCPBG (15 mg/kg); granisetron (3mg/kg); tacrolimus (1mg/kg); or tacrolimus (1mg/kg) plus tropisetron (3mg/kg) were administered intraperitoneally 1h prior to embolization. Behavioral scores and infarct volume as well as myeloperoxidase (MPO) activity and tumor necrosis factor-alpha (TNF-α) level were determined in the ipsilateral cortex 4h and 48 h following stroke induction. Forty-eight hours after embolization, tropisetron (1 or 3mg/kg), tropisetron (3mg/kg) plus mCPBG (15 mg/kg), tacrolimus (1mg/kg), or tacrolimus (1mg/kg) plus tropisetron (3mg/kg) significantly curtailed brain infarction, improved behavioral scores, diminished elevated tissue MPO activity, and reduced TNF-α levels compared to control group (n=6; P<0.05). mCPBG or granisetron had no effect on the mentioned parameters. Tropisetron attenuates brain damage after a thromboembolic event. Beneficial effects of tropisetron in this setting are receptor independent.
authors: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
authors: Reza
authors: R
authors: Rahimian
authors: Ali
authors: A
authors: Daneshmand
authors: Shahram Ejtemaei
authors: SE
authors: Mehr
authors: Anita
authors: A
authors: Barzegar-Fallah
authors: Sanaz
authors: S
authors: Mohammadi-Rick
authors: Gohar
authors: G
authors: Fakhfouri
authors: Alireza P
authors: AP
authors: Shabanzadeh
authors: Ahmad Reza
authors: AR
authors: Dehpour
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001645:Biguanides / Q000627:therapeutic use; D001784:Blood Gas Analysis / Q000379:methods; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology*; D002540:Cerebral Cortex / Q000201:enzymology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use*; D007511:Ischemia / Q000150:complications; D008297:Male; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy / Q000209:etiology; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D020521:Stroke / Q000150:complications* / Q000209:etiology; D016559:Tacrolimus / Q000627:therapeutic use; D000077526:Tropisetron; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001645:Biguanides; D007166:Immunosuppressive Agents; D007211:Indoles; D012702:Serotonin Antagonists; D014409:Tumor Necrosis Factor-alpha; D000077526:Tropisetron; C065734:1-(3-chlorophenyl)biguanide; D009195:Peroxidase; D016559:Tacrolimus