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Matrix metalloproteinase-2 and metalloproteinase-9 activities are associated with blood-brain barrier dysfunction in an animal model of severe sepsis
- Source :
- Molecular neurobiology. 48(1)
- Publication Year :
- 2013
-
Abstract
- There is no description on the mechanisms associated with blood–brain barrier (BBB) disruption during sepsis development. Thus, we here determined changes in permeability of the BBB in an animal model of severe sepsis and the role of matrix metalloproteinase (MMP)-2 and MMP-9 in the dysfunction of the BBB. Sepsis was induced in Wistar rats by cecal ligation and perforation. BBB permeability was assessed using the Evans blue dye method. The content of MMP-2 and MMP-9 in the cerebral microvessels was determined by western blot. The activity of MMP-2 and MMP-9 was determined using zymography. An inhibitor of MMP-2 and MMP-9 or specific inhibitors of MMP-2 or MMP-9 were administered to define the role of MMPs on BBB permeability, brain inflammatory response, and sepsis-induced cognitive alterations. The increase of BBB permeability is time-related to the increase of MMP-9 and MMP-2 in the microvessels, both in cortex and hippocampus. Using an MMP-2 and MMP-9 inhibitor, or specific MMP-2 or MMP-9 inhibitors, the increase in the permeability of the BBB was reversed. This was associated with lower brain levels of interleukin (IL)-6 and lower oxidative damage. In contrast, only the inhibition of both MMP-9 and MMP-2 was able to improve acute cognitive alterations associated with sepsis. In conclusion, MMP-2 and MMP-9 activation seems to be a major step in BBB dysfunction, but BBB dysfunction seems not to be associated with acute cognitive dysfunction during sepsis development.
- Subjects :
- Male
Perforation (oil well)
Neuroscience (miscellaneous)
Pharmacology
Matrix metalloproteinase
Biology
Matrix Metalloproteinase Inhibitors
Blood–brain barrier
medicine.disease_cause
Permeability
Sepsis
Cellular and Molecular Neuroscience
chemistry.chemical_compound
medicine
Animals
Rats, Wistar
Evans Blue
Metalloproteinase
Behavior, Animal
Interleukin
medicine.disease
Rats
Disease Models, Animal
Oxidative Stress
medicine.anatomical_structure
nervous system
Neurology
chemistry
Matrix Metalloproteinase 9
Blood-Brain Barrier
Immunology
Microvessels
cardiovascular system
Matrix Metalloproteinase 2
Oxidative stress
Subjects
Details
- ISSN :
- 15591182
- Volume :
- 48
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Molecular neurobiology
- Accession number :
- edsair.doi.dedup.....017aa17ace8b967dab646d923984b3ec