title: Therapeutic benefits of combined treatment with tissue plasminogen activator and 2-(4-methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside in an animal model of ischemic stroke.
abstract: Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke, but tPA therapy is limited by a short therapeutic window and some adverse side effects. 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside, a salidroside analog (code-named SalA-4g), has shown potent neuroprotective effects. In this study, a rat model of embolic middle cerebral artery occlusion (MCAO) was used to mimic ischemic stroke. The embolic MCAO rats were intravenously (iv) injected with tPA alone, SalA-4g alone, or a combination of tPA and SalA-4g. Compared to treatment with tPA alone at 4h post MCAO, combined treatment with tPA at 4h post MCAO and SalA-4g starting at 4h post MCAO and continuing for 3days at an interval of 24h significantly reduced neurological deficits and infarct volume, and significantly inhibited the intracerebral bleeding, edema formation, neuronal loss, and cellular apoptosis in the ischemic brain. Our results suggested that additive neuroprotective actions of SalA-4g contributed to widening the therapeutic window of tPA therapy and ameliorating its side effects in treating MCAO rats. The therapeutic benefits of combined treatment with tPA and SalA-4g for ischemic stroke might be associated with its effects on cerebral glucose metabolism.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Collaborative Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Yu
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Collaborative Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Collaborative Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, China.
authors.forename: Yuntian
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Collaborative Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Collaborative Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Collaborative Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, China. Electronic address: dingfei@ntu.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Ding
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000188:drug therapy; D003131:Combined Modality Therapy / Q000379:methods; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
chemical_list: C000589286:2-(4-methoxyphenyl)ethyl-2-acetamido-2-deoxyglucopyranoside; D005343:Fibrinolytic Agents; D018696:Neuroprotective Agents; D010959:Tissue Plasminogen Activator; D000117:Acetylglucosamine
keywords: 2-(4-methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside; ischemic stroke; neuroprotection; thrombolytic therapy; tissue plasminogen activator