N2 extenuates experimental ischemic stroke through platelet aggregation inhibition.

Abstract

INTRODUCTION:

Thromboxane A2 (TXA2) can induce the platelet aggregation and lead to thrombosis. This will cause the low-reflow phenomenon after ischemic stroke and aggravate the damage of brain issues. Therefore, it is potential to develop the drugs inhibiting TXA2 pathway to treat cerebral ischemia.

AIM:

This study aims to prove the protective effect of N2 (4-(2-(1H-imidazol-1-yl) ethoxy)-3-methoxybenzoic acid) on focal cerebral ischemia and reperfusion injury through platelet aggregation inhibition.

MATERIALS AND METHODS:

Middle cerebral artery occlusion/reperfusion (MCAO/R) is used as the animal model. Neurological deficit score, Morris water maze, postural reflex test, Limb-use asymmetry test, infarct volume, and water content were performed to evaluate the protective effect of N2 in MCAO/R rats. 9, 11-dieoxy-11α, 9α-methanoepoxyprostaglandin F2α (U46619) or adenosine diphosphate (ADP) was used as the inducer of platelet aggregation.

RESULTS AND CONCLUSIONS:

N2 can improve the motor function, learning and memory ability in MCAO/R rats while reducing the infarct volume. N2 can inhibit TXA2 formation but promote PGI2, and can inhibit platelet aggregation induced by U46619 and ADP. Further, N2 inhibits thrombosis with a minor adverse effect of bleeding than Clopidogrel. In conclusion, N2 can produce the protective effect on MCAO/R brain injury through inhibiting TXA2 formation, platelet aggregation and thrombosis.

• Authors: Lijian Yang, Xi Chen, Siqi Wang, Yuxiang Fei, Ding Wang, Yunman Li, Guangwei He, Qiang Wu, Shaoxing Chu, Weirong Fang
• Journal: Thrombosis research (Thromb Res) Vol. 136 Issue 6 Pg. 1310-7 (Dec 2015) ISSN: 1879-2472 [Electronic] United States
• PMID: 26553017 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• 4-(2-(1H-imidazol-1-yl)ethoxy)-3-methoxybenzoic acid
• Imidazoles
• dazoxiben
• Thromboxane A2
• Adenosine Diphosphate
• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
• Epoprostenol
• Vanillic Acid

Topics

• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid (chemistry)
• Adenosine Diphosphate (chemistry)
• Animals
• Arteriovenous Shunt, Surgical
• Blood Coagulation
• Brain (pathology)
• Brain Ischemia (drug therapy)
• Edema (pathology)
• Enzyme-Linked Immunosorbent Assay
• Epoprostenol (chemistry)
• Female
• Imidazoles (chemistry)
• Male
• Maze Learning
• Platelet Aggregation (drug effects)
• Rats
• Rats, Sprague-Dawley
• Stroke (drug therapy)
• Thrombosis (physiopathology)
• Thromboxane A2 (chemistry)
• Vanillic Acid (analogs & derivatives, chemistry)