title: A cross-laboratory preclinical study on the effectiveness of interleukin-1 receptor antagonist in stroke.
abstract: Stroke represents a global challenge and is a leading cause of permanent disability worldwide. Despite much effort, translation of research findings to clinical benefit has not yet been successful. Failure of neuroprotection trials is considered, in part, due to the low quality of preclinical studies, low level of reproducibility across different laboratories and that stroke co-morbidities have not been fully considered in experimental models. More rigorous testing of new drug candidates in different experimental models of stroke and initiation of preclinical cross-laboratory studies have been suggested as ways to improve translation. However, to our knowledge, no drugs currently in clinical stroke trials have been investigated in preclinical cross-laboratory studies. The cytokine interleukin 1 is a key mediator of neuronal injury, and the naturally occurring interleukin 1 receptor antagonist has been reported as beneficial in experimental studies of stroke. In the present paper, we report on a preclinical cross-laboratory stroke trial designed to investigate the efficacy of interleukin 1 receptor antagonist in different research laboratories across Europe. Our results strongly support the therapeutic potential of interleukin 1 receptor antagonist in experimental stroke and provide further evidence that interleukin 1 receptor antagonist should be evaluated in more extensive clinical stroke trials.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Maysami
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Raymond
authors.initials: R
authors.lastname: Wong
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK Department of Pharmacology, Medicine School, University Complutense of Madrid, Spain.
authors.forename: Jesus M
authors.initials: JM
authors.lastname: Pradillo
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK Laboratory of Neuroimmunology, Institute of Experimental Medicine, Budapest, Hungary.
authors.forename: Adam
authors.initials: A
authors.lastname: Denes
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Hiramani
authors.initials: H
authors.lastname: Dhungana
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Tarja
authors.initials: T
authors.lastname: Malm
authors.affiliation: Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Koistinaho
authors.affiliation: Inserm, Inserm UMR-S U919, Université de Caen Basse Normandie, GIP Cyceron, Caen, France.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Orset
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany Department of Pharmaceutical Sciences, North South University, Bashundhara, Dhaka, Bangladesh.
authors.forename: Mahbubur
authors.initials: M
authors.lastname: Rahman
authors.affiliation: Inserm, Inserm UMR-S U919, Université de Caen Basse Normandie, GIP Cyceron, Caen, France.
authors.forename: Marina
authors.initials: M
authors.lastname: Rubio
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaninger
authors.affiliation: Inserm, Inserm UMR-S U919, Université de Caen Basse Normandie, GIP Cyceron, Caen, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
authors.affiliation: Stroke, Division of Clinical Neuroscience, University of Nottingham, City Hospital Campus, Nottingham, UK.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Bath
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Rothwell
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK stuart.allan@manchester.ac.uk.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Allan
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D001929:Brain Edema / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000276:immunology; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D018696:Neuroprotective Agents; D017472:Receptors, Interleukin-1
keywords: Acute stroke; animal models; experimental; inflammation; neuroprotection