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

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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.
RGD ID: 13208507
Pubmed: PMID:17983428   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1365-2990.2007.00889.x   (Journal Full-text)


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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Serpine1  (serpin family E member 1)

Genes (Mus musculus)
Serpine1  (serine (or cysteine) peptidase inhibitor, clade E, member 1)

Genes (Homo sapiens)
SERPINE1  (serpin family E member 1)


Additional Information