Abstract
Inflammation can contribute to brain injury, such as that resulting from ischemia or trauma. The authors have previously shown that the cytokine interferon-beta (IFN-beta) affords protection against ischemic brain injury, which was associated with a diminished infiltration of neutrophils and a reduction in blood-brain barrier (BBB) disruption. The goal of the current study was to directly assess the effects of IFN-beta on neutrophil infiltration, with the use of an in vivo assay of neutrophil infiltration with relevance to ischemic brain injury. Intrastriatal injection of recombinant rat cytokine-induced neutrophil chemoattractant-1, a member of the interleukin-8 family (1 microg in 1 microl), triggered massive infiltration of neutrophils and extensive BBB disruption 6 hours later, as measured using immunofluorescence microscopy and magnetic resonance imaging in the rat, respectively. Depleting the animals of neutrophils before interleukin-8 injection prevented BBB disruption. Treatment with IFN-beta (5 x 106 U/kg) almost completely prevented neutrophil infiltration and attenuated BBB damage. Gelatinase zymography showed matrix metalloproteinase-9 expression in the ipsilateral striatum after interleukin-8 injection. Both neutrophil depletion and IFN-beta treatment downregulated matrix metalloproteinase-9. IFN-beta has already been approved for human use as a treatment for the chronic inflammatory disorder multiple sclerosis. The potential value of IFN-beta as a treatment that can attenuate acute brain inflammation is considered.
Original language | English |
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Pages (from-to) | 1060-9 |
Number of pages | 10 |
Journal | Journal of cerebral blood flow and metabolism |
Volume | 23 |
Issue number | 9 |
DOIs | |
Publication status | Published - Sept 2003 |
Keywords
- Animals
- Blood Volume
- Blood-Brain Barrier/drug effects
- Brain/anatomy & histology
- Cerebrovascular Circulation
- Endothelium, Vascular/cytology
- Hemodynamics
- Humans
- Intercellular Adhesion Molecule-1/metabolism
- Interferon-beta/immunology
- Interleukin-8/immunology
- Magnetic Resonance Imaging
- Male
- Matrix Metalloproteinase 9/metabolism
- Neurons/cytology
- Neutrophil Infiltration
- Neutrophils/immunology
- Rats
- Rats, Inbred F344
- Recombinant Proteins/pharmacology