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.
| Original language | English |
|---|---|
| Article number | 211 |
| Journal | Journal of Neuroinflammation |
| Volume | 12 |
| Pages (from-to) | 1-18 |
| ISSN | 1742-2094 |
| DOIs | |
| Publication status | Published - 18 Nov 2015 |
Keywords
- Animals
- B-Lymphocytes
- Brain
- Brain Ischemia
- Cytokines
- Hand Strength
- Infarction, Middle Cerebral Artery
- Inflammation
- Interferon-beta
- Ischemic Attack, Transient
- Leukocytes
- Lymphocyte Count
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Postural Balance
- Receptors, Interferon
- Spleen
- Stroke