title: Neuroprotection and thrombolysis: combination therapy in acute ischaemic stroke.
abstract: The administration of oral aspirin within 48 h and tissue plasminogen activator within 3 h of ischaemic stroke onset remain the only treatments that have been shown to have clinical benefit. There has been much excitement about neuroprotection over the last two decades, as it may minimise the harmful effects of ischaemic neuronal damage. Although each step along the ischaemic cascade offers a potential target for therapeutic intervention, and neuroprotection has shown benefit in animal studies, this has been difficult to translate to humans. Some hope has been offered by the recent finding that the free radical scavenger NXY-059 may improve outcomes in patients presenting within 6 h of onset of ischaemic stroke. There is logic to the idea that neuroprotection may be most effective when reperfusion has occurred with thrombolysis, as the neuroprotectant will have greater access to ischaemic tissue and the opportunity is presented to minimise free radical-mediated reperfusion injury. Numerous studies in animal models support this view, but the concept has not, as yet, been rigorously tested in humans.
authors.affiliation: National Stroke Research Institute, Level 1, Neurosciences Building, Austin Health, University of Melbourne, 300 Waterdale Road, Heidleberg Heights, Victoria 3081, Australia.
authors.forename: John V
authors.initials: JV
authors.lastname: Ly
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Zavala
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
mesh_terms: D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D018755:GABA Agonists / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009589:Nitrogen Oxides / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D026941:Sodium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D001557:Benzenesulfonates; D005343:Fibrinolytic Agents; D016166:Free Radical Scavengers; D018755:GABA Agonists; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; D010880:Piperidines; D026941:Sodium Channel Blockers; D013844:Thiazoles; C120851:disufenton sodium; D010959:Tissue Plasminogen Activator; C097722:lubeluzole