title: N2 extenuates experimental ischemic stroke through platelet aggregation inhibition.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  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.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Fei
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Ding
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: yunmanlicpu@hotmail.com.
authors.forename: Yunman
authors.initials: Y
authors.lastname: Li
authors.affiliation: Hefei Yigong Medicine Co., Ltd., Hefei 230088, PR China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: He
authors.affiliation: Hefei Yigong Medicine Co., Ltd., Hefei 230088, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Hefei Yigong Medicine Co., Ltd., Hefei 230088, PR China.
authors.forename: Shaoxing
authors.initials: S
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: weirongfang@163.com.
authors.forename: Weirong
authors.initials: W
authors.lastname: Fang
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000737:chemistry; D000244:Adenosine Diphosphate / Q000737:chemistry; D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D001777:Blood Coagulation; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy*; D004487:Edema / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D011464:Epoprostenol / Q000737:chemistry; D005260:Female; D007093:Imidazoles / Q000737:chemistry; D008297:Male; D018782:Maze Learning; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy*; D013927:Thrombosis / Q000503:physiopathology; D013928:Thromboxane A2 / Q000737:chemistry; D014641:Vanillic Acid / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: C000597740:4-(2-(1H-imidazol-1-yl)ethoxy)-3-methoxybenzoic acid; D007093:Imidazoles; C029166:dazoxiben; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011464:Epoprostenol; D014641:Vanillic Acid
keywords: Ischemic stroke; N2; Platelet aggregation; Thromboxane A(2)