title: Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia.
abstract: BACKGROUND
  Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death and promotes functional recovery after stroke. However, the core actions of endogenous IFN-β signaling in stroke are unclear.
  
  
  METHODS
  To address this question, we used two clinically relevant models of focal cerebral ischemia, transient and permanent middle cerebral artery occlusion, and two genetically modified mouse lines, lacking either IFN-β or its receptor, the IFN-α/β receptor. Subsets of inflammatory and immune cells isolated from the brain, blood, and spleen were studied using flow cytometry. Sensorimotor deficits were assessed by a modified composite neuroscore, the rotating pole and grip strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity.
  
  
  RESULTS
  Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-βKO mice, we found a higher percentage of total B cells but a similar percentage of mature and activated B cells, collectively indicating a higher proliferation rate. The additional differential regulation of circulating cytokines and splenic immune cell populations in wild-type and IFN-βKO mice further supports an important immunoregulatory function of IFN-β in stroke. Moreover, we observed a significant weight loss 2-3 days and a reduction in grip strength 2 days after stroke in the IFN-βKO group, while endogenous IFN-β signaling did not affect the infarct volume.
  
  
  CONCLUSIONS
  We conclude that endogenous IFN-β signaling attenuates local inflammation, regulates peripheral immune cells, and, thereby, may contribute positively to stroke outcome.
authors.affiliation: Laboratory for Experimental Brain Research, Department of Clinical Sciences, Lund University, BMC A13, Sölvegatan 17, 22184, Lund, Sweden. ana.inacio@inserm.fr.|Present Address: INMED, INSERM U901, Parc Scientifique de Luminy, 163 route de Luminy, BP13, 13273, Marseille cedex 09, France. ana.inacio@inserm.fr.|Present Address: Aix-Marseille Université, UMR S901, 13009, Marseille, France. ana.inacio@inserm.fr.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Inácio
authors.affiliation: Neuroinflammation Unit, Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200, Copenhagen N, Denmark.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsloewsvej 21, st + 25, 2, 5000, Odense C, Denmark.
authors.forename: Bettina H
authors.initials: BH
authors.lastname: Clausen
authors.affiliation: Experimental Neuroinflammation Laboratory, Department of Experimental Medical Sciences, Lund University, BMC B11, Sölvegatan 19, 22184, Lund, Sweden.
authors.forename: Martina
authors.initials: M
authors.lastname: Svensson
authors.affiliation: Laboratory for Experimental Brain Research, Department of Clinical Sciences, Lund University, BMC A13, Sölvegatan 17, 22184, Lund, Sweden.|7Present Address: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen N, 2200, Denmark.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kucharz
authors.affiliation: Experimental Neuroinflammation Laboratory, Department of Experimental Medical Sciences, Lund University, BMC B11, Sölvegatan 19, 22184, Lund, Sweden.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Laboratory for Experimental Brain Research, Department of Clinical Sciences, Lund University, BMC A13, Sölvegatan 17, 22184, Lund, Sweden.
authors.forename: Totte
authors.initials: T
authors.lastname: Stankovich
authors.affiliation: Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsloewsvej 21, st + 25, 2, 5000, Odense C, Denmark.
authors.forename: Reza
authors.initials: R
authors.lastname: Khorooshi
authors.affiliation: Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsloewsvej 21, st + 25, 2, 5000, Odense C, Denmark.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Lambertsen
authors.affiliation: Neuroinflammation Unit, Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, 2200, Copenhagen N, Denmark. shohreh.issazadeh@bric.ku.dk.
authors.forename: Shohreh
authors.initials: S
authors.lastname: Issazadeh-Navikas
authors.affiliation: Laboratory for Experimental Brain Research, Department of Clinical Sciences, Lund University, BMC A13, Sölvegatan 17, 22184, Lund, Sweden.|Experimental Neuroinflammation Laboratory, Department of Experimental Medical Sciences, Lund University, BMC B11, Sölvegatan 19, 22184, Lund, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Deierborg
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology* / Q000523:psychology; D016207:Cytokines / Q000097:blood; D018737:Hand Strength / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D007249:Inflammation / Q000473:pathology*; D016899:Interferon-beta / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D004856:Postural Balance; D017471:Receptors, Interferon / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology; D020521:Stroke / Q000473:pathology* / Q000523:psychology
chemical_list: D016207:Cytokines; D017471:Receptors, Interferon; D016899:Interferon-beta