Journal
JOURNAL OF NEUROINFLAMMATION
Volume 12, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s12974-015-0427-0
Keywords
Cytokines; IFN-alpha/beta receptor; Interferon-beta; Inflammatory and immune cells; Knockout mice; Middle cerebral artery occlusion
Categories
Funding
- Fundacao para a Ciencia e a Tecnologia, Portugal
- A.E. Berger, The Crafoord Foundation, Sweden
- G.E. Kock's Foundation, Sweden
- Gyllenstiernska Krapperup Foundation, Sweden
- Royal Physiographic Society in Lund, Sweden
- Swedish National Stroke Foundation, Sweden
- Swedish Research Council, Sweden [2012-2229]
- Danish Independent Research Council, Denmark
- Lundbeck Foundation, Denmark
- Brodrene Hartmann Fond, Denmark
- Savvaerksejer Jeppe Juhl og Hustru Ovita Juhls Mindelegat, Denmark
- Agency for Research and Innovation, Council for Health Research, Denmark
- Lundbeck Foundation [R108-2012-10312] Funding Source: researchfish
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Background: Interferon (IFN)-beta 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-beta, by limiting inflammation, decreases neuronal death and promotes functional recovery after stroke. However, the core actions of endogenous IFN-beta 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-beta or its receptor, the IFN-alpha/beta 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-beta knockout (IFN-beta KO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-beta KO mice showed a higher number of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-beta KO 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-beta KO mice further supports an important immunoregulatory function of IFN-beta 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-beta KO group, while endogenous IFN-beta signaling did not affect the infarct volume. Conclusions: We conclude that endogenous IFN-beta signaling attenuates local inflammation, regulates peripheral immune cells, and, thereby, may contribute positively to stroke outcome.
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