Therapeutic effects of tetramethylpyrazine nitrone in rat ischemic stroke models.

Abstract

Free radical-mediated neuronal cell damage is an important pathological process in ischemic stroke. We have previously reported a novel dual-functional agent, 2-[[(1,1-dimethylethyl)oxidoimino]-methyl]-3,5,6-trimethylpyrazine (TBN), a derivative of tetramethylpyrazine armed with anitrone moiety. In this report, we further evaluate TBN'stherapeutic parameters in a rat middle cerebral artery occlusion (MCAO) model. Its abilities to cross the blood-brain barrier, scavenge free radicals, and inhibit Ca(2+) influx were also investigated. TBN showed significant activity in both the transient MCAO (t-MCAO) and permanent MCAO (p-MCAO) stroke models in the rat. The therapeutic time window is 8 hr in the t-MCAO model. TBN readily crossed the blood-brain barrier and in vitro had strong activity in neutralizing ·OH, O(-)(2)·, and ONOO(-) and significantly decreased intracellular Ca(2+) concentration. TBN is a promising new treatment forischemic stroke, with multiple mechanisms of action. It blocks Ca(2+) overload and neutralizes ·OH, O(-)(2)·, and ONOO(-).

• Authors: Yewei Sun, Pei Yu, Gaoxiao Zhang, Liang Wang, Haijing Zhong, Ziyuan Zhai, Linda Wang, Yuqiang Wang
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 90 Issue 8 Pg. 1662-9 (Aug 2012) ISSN: 1097-4547 [Electronic] United States
• PMID: 22431378 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Free Radical Scavengers
• Neuroprotective Agents
• Pyrazines
• tetramethylpyrazine

Topics

• Animals
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Free Radical Scavengers (administration & dosage)
• Infarction, Middle Cerebral Artery (drug therapy)
• Male
• Neuroprotective Agents (administration & dosage)
• Pyrazines (administration & dosage)
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (drug effects)