Chronic relapsing experimental allergic encephalomyelitis (CREAE) in plasminogen activator inhibitor-1 knockout mice: the effect of fibrinolysis during neuroinflammation.

Authors: East, E  Gveric, D  Baker, D  Pryce, G  Lijnen, H R  Cuzner, M L 
Citation: East E, etal., Neuropathol Appl Neurobiol. 2008 Apr;34(2):216-30. Epub 2007 Nov 5.
Pubmed: (View Article at PubMed) PMID:17983428
DOI: Full-text: DOI:10.1111/j.1365-2990.2007.00889.x

UNLABELLED: During neuroinflammation in multiple sclerosis (MS) fibrinogen, not normally present in the brain or spinal cord, enters the central nervous system through a compromised blood-brain barrier. Fibrin deposited on axons is ineffectively removed by tissue plasminogen activator (tPA), a key contributory factor being the upregulation of plasminogen activator inhibitor-1 (PAI-1).
AIMS: This study investigated the role of PAI-1 during experimental neuroinflammatory disease.
METHODS: Chronic relapsing experimental allergic encephalomyelitis (CREAE), a model of MS, was induced with spinal cord homogenate in PAI-1 knockout (PAI-1(-/-)) and wild type (WT) mice, backcrossed onto the Biozzi background.
RESULTS: Disease incidence and clinical severity were reduced in PAI-1(-/-) mice, with animals developing clinical signs significantly later than WTs. Clinical relapses were absent in PAI-1(-/-) mice and the subsequent reduction in neuroinflammation was coupled with a higher capacity for fibrinolysis in spinal cord samples from PAI-1(-/-) mice, in association with increased tPA activity. Axonal damage was less apparent in PAI-1(-/-) mice than in WTs, implicating fibrin in both inflammatory and degenerative events during CREAE.
CONCLUSIONS: PAI-1 is a potential target for therapy in neuroinflammatory degenerative diseases, allowing effective fibrin removal and potentially reducing relapse rate and axonal damage.


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CRRD Object Information
CRRD ID: 13208507
Created: 2017-08-09
Species: All species
Last Modified: 2017-08-09
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.