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: Reza Rahimian, Ali Daneshmand, Shahram Ejtemaei Mehr, Anita Barzegar-Fallah, Sanaz Mohammadi-Rick, Gohar Fakhfouri, Alireza P Shabanzadeh, Ahmad Reza Dehpour
• Journal: Brain research (Brain Res) Vol. 1392 Pg. 101-9 (May 25 2011) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 21447327 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Biguanides
• Immunosuppressive Agents
• Indoles
• Serotonin Antagonists
• Tumor Necrosis Factor-alpha
• Tropisetron
• 1-(3-chlorophenyl)biguanide
• Peroxidase
• Tacrolimus

Topics

• Analysis of Variance
• Animals
• Biguanides (therapeutic use)
• Blood Gas Analysis (methods)
• Brain Edema (etiology, prevention & control)
• Brain Infarction (etiology, prevention & control)
• Brain Injuries (drug therapy, etiology)
• Cerebral Cortex (enzymology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Immunosuppressive Agents (therapeutic use)
• Indoles (therapeutic use)
• Ischemia (complications)
• Male
• Nervous System Diseases (drug therapy, etiology)
• Peroxidase (metabolism)
• Rats
• Rats, Wistar
• Seizures (drug therapy, etiology)
• Serotonin Antagonists (therapeutic use)
• Stroke (complications, etiology)
• Tacrolimus (therapeutic use)
• Tropisetron
• Tumor Necrosis Factor-alpha (metabolism)