naa a22 4500 510800025 CHVBK 20180411083351.0 cr unu---uuuuu 180411e20130201xx s 000 0 eng 10.1007/s12028-012-9692-2 doi (NATIONALLICENCE)springer-10.1007/s12028-012-9692-2 Effect of Interferon-β on Neuroinflammation, Brain Injury and Neurological Outcome After Experimental Subarachnoid Hemorrhage [Elektronische Daten] [Ivo Tiebosch, Rick Dijkhuizen, Pieter Cobelens, Mark Bouts, René Zwartbol, Peter van der Meide, Walter van den Bergh] Introduction: Aneurysmal subarachnoid hemorrhage (SAH) has a poor outcome, particularly attributed to progressive injury after the initial incident. Several studies suggest a critical role for inflammation in lesion progression after SAH. Our goal was to test whether treatment with anti-inflammatory interferon-β, which has shown promise as a therapeutic agent in experimental ischaemic stroke, can protect the brain after SAH. Methods: SAH was induced in adult male Wistar rats by puncturing the intracranial bifurcation of the right internal carotid artery. Treatment effects of daily interferon-β (n=16) or vehicle (n=14) injections were serially evaluated with multiparametric MRI and behavioral tests from day 0 to 7, in compliance with recent recommendations for pre-clinical drug testing. Outcome measures included neurological status, brain lesion volume, blood-brain barrier (BBB) leakage, and levels of inflammatory markers. Results: In animals that survived up to 7days post-SAH, we found no significant differences between vehicle- and interferon-β-treated animals with respect to final neurological score (14.3±1.0 vs. 13.0±2.2), brain lesion size on T2-weighted MR images (59±83 vs. 124±99mm3), BBB leakage (0.26±0.05 vs. 0.22±0.08 contrast-induced relative MR signal change), upregulation of brain RNA for cytokines, chemokines and cell adhesion molecules, and increased neutrophil activation. Conclusions: In contrast to previously published findings in experimental ischemic stroke models, interferon-β has no clear efficacy to protect the brain after SAH. In line with recent highlighting of the significance of negative findings, our data currently do not recommend clinical testing of interferon-β to prevent neurological damage in SAH patients. Springer Science+Business Media, LLC, 2012 Cerebral injury nationallicence Inflammation nationallicence Interferon-β nationallicence MRI nationallicence Rats nationallicence Subarachnoid hemorrhage nationallicence Tiebosch Ivo Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands aut Dijkhuizen Rick Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands aut Cobelens Pieter Department of Intensive Care Medicine, Room Q04.460, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands aut Bouts Mark Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands aut Zwartbol René Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands aut van der Meide Peter Cytokine Biology Unit, Central Laboratory Animal Institute, Utrecht University, Utrecht, The Netherlands aut van den Bergh Walter Department of Intensive Care Medicine, Room Q04.460, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands aut Neurocritical Care Humana Press Inc 18/1(2013-02-01), 96-105 1541-6933 18:1<96 2013 18 12028 https://doi.org/10.1007/s12028-012-9692-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12028-012-9692-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tiebosch Ivo Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Dijkhuizen Rick Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Cobelens Pieter Department of Intensive Care Medicine, Room Q04.460, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Bouts Mark Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- Zwartbol René Biomedical MR Imaging and Spectroscopy Group, Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- van der Meide Peter Cytokine Biology Unit, Central Laboratory Animal Institute, Utrecht University, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- van den Bergh Walter Department of Intensive Care Medicine, Room Q04.460, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands aut NATIONALLICENCE 773 0- Neurocritical Care Humana Press Inc 18/1(2013-02-01), 96-105 1541-6933 18:1<96 2013 18 12028 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer