RGD Reference Report - Interferon-beta blocks infiltration of inflammatory cells and reduces infarct volume after ischemic stroke in the rat. - Rat Genome Database

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Interferon-beta blocks infiltration of inflammatory cells and reduces infarct volume after ischemic stroke in the rat.

Authors: Veldhuis, Wouter B  Derksen, Joris W  Floris, Sarah  Van Der Meide, Peter H  De Vries, Helga E  Schepers, Janneke  Vos, Ine M P  Dijkstra, Christien D  Kappelle, L Jaap  Nicolay, Klaas  Bär, Peter R 
Citation: Veldhuis WB, etal., J Cereb Blood Flow Metab. 2003 Sep;23(9):1029-39. doi: 10.1097/01.WCB.0000080703.47016.B6.
RGD ID: 401851924
Pubmed: PMID:12973019   (View Abstract at PubMed)
DOI: DOI:10.1097/01.WCB.0000080703.47016.B6   (Journal Full-text)

The inflammatory response that exacerbates cerebral injury after ischemia is an attractive therapeutic target: it progresses over days and strongly contributes to worsening of the neurologic outcome. The authors show that, after transient ischemic injury to the rat brain, systemic application of interferon-beta (IFN-beta), a cytokine with antiinflammatory properties, attenuated the development of brain infarction. Serial magnetic resonance imaging (MRI) showed that IFN-beta treatment reduced lesion volume on diffusion-weighted MRI by 70% (P < 0.01) at 1 day after stroke. IFN-beta attenuated the leakage of contrast agent through the blood-brain barrier (P < 0.005), indicating a better-preserved blood-brain barrier integrity. Both control and IFN-beta-treated animals showed a similar degree of relative hyperperfusion of the lesioned hemisphere, indicating that neuroprotection by IFN-beta was not mediated by improved cerebral perfusion as assessed 24 hours after stroke onset. IFN-beta treatment resulted in an 85% reduction (P < 0.0001) in infarct volume 3 weeks later, as determined from T2-weighted MRI and confirmed by histology. This effect was achieved even when treatment was started 6 hours after stroke onset. Quantitative immunohistochemistry at 24 hours after stroke onset showed that IFN-beta almost completely prevented the infiltration of neutrophils and monocytes into the brain. Gelatinase zymography showed that this effect was associated with a decrease in matrix metalloproteinase-9 expression. In conclusion, treatment with the antiinflammatory cytokine IFN-beta affords significant neuroprotection against ischemia/reperfusion injury, and within a relatively long treatment window. Because IFN-beta has been approved for clinical use, it may be rapidly tested in a clinical trial for its efficacy against human stroke.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IFNB1Humantransient cerebral ischemia amelioratesISOIfnb1 (Rattus norvegicus) RGD 
Ifnb1Rattransient cerebral ischemia amelioratesIDA  RGD 
Ifnb1Mousetransient cerebral ischemia amelioratesISOIfnb1 (Rattus norvegicus) RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ifnb1Ratnegative regulation of blood-brain barrier permeability  IDA  RGD 
Ifnb1Ratnegative regulation of neuroinflammatory response  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ifnb1  (interferon beta 1)

Genes (Mus musculus)
Ifnb1  (interferon beta 1, fibroblast)

Genes (Homo sapiens)
IFNB1  (interferon beta 1)


Additional Information