Endogenous IFN-ß signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia.
J Neuroinflammation
; 12: 211, 2015 Nov 18.
Article
em En
| MEDLINE
| ID: mdl-26581581
ABSTRACT
BACKGROUND:
Interferon (IFN)-ß 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-ß, by limiting inflammation, decreases neuronal death and promotes functional recovery after stroke. However, the core actions of endogenous IFN-ß 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-ß or its receptor, the IFN-α/ß 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-ß knockout (IFN-ßKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-ßKO mice showed a higher number of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-ßKO 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-ßKO mice further supports an important immunoregulatory function of IFN-ß 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-ßKO group, while endogenous IFN-ß signaling did not affect the infarct volume.CONCLUSIONS:
We conclude that endogenous IFN-ß signaling attenuates local inflammation, regulates peripheral immune cells, and, thereby, may contribute positively to stroke outcome.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Isquemia Encefálica
/
Interferon beta
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Acidente Vascular Cerebral
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Inflamação
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article