RGD Reference Report - Lovastatin attenuates nerve injury in an animal model of Guillain-Barre syndrome. - Rat Genome Database

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Lovastatin attenuates nerve injury in an animal model of Guillain-Barre syndrome.

Authors: Sarkey, JP  Richards, MP  Stubbs EB, JR 
Citation: Sarkey JP, etal., J Neurochem. 2007 Mar;100(5):1265-77. Epub 2006 Dec 22.
RGD ID: 5508466
Pubmed: PMID:17286627   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1471-4159.2006.04309.x   (Journal Full-text)

Statins, widely used as clinically effective inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, exhibit anti-inflammatory properties that may be of therapeutic benefit for the management of some neurological disorders. In this study, a short-term course of lovastatin treatment is shown to markedly inhibit the development of experimental autoimmune neuritis (EAN) in the absence of hepatotoxic or myotoxic complications. Independent of cholesterol reduction, lovastatin treatment prevented EAN-induced peripheral nerve conduction deficits and morphologic nerve injury. Co-administration with mevalonate neutralized the prophylactic effects of lovastatin. When administered therapeutically, lovastatin significantly shortened the disease course. Autoreactive immunity, measured in vitro by myelin-stimulated proliferation of splenocytes, was significantly diminished by in vivo lovastatin treatment. Th1-dominant immune responses, measured by cytokine profiling, however, were not affected by lovastatin. Sciatic nerves of lovastatin-treated immunized rats showed markedly reduced levels of cellular infiltrates. Treating peripheral nerve endothelial monolayers with lovastatin significantly inhibited the in vitro migration of autoreactive splenocytes. Together, these data demonstrate that a short-term course of lovastatin attenuates the development and progression of EAN in Lewis rats by limiting the proliferation and migration of autoreactive leukocytes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Autoimmune Neuritis disease_progressionISOHmgcr (Rattus norvegicus)5508466; 5508466 RGD 
Experimental Autoimmune Neuritis disease_progressionIMP 5508466 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hmgcr  (3-hydroxy-3-methylglutaryl-CoA reductase)

Genes (Mus musculus)
Hmgcr  (3-hydroxy-3-methylglutaryl-Coenzyme A reductase)

Genes (Homo sapiens)
HMGCR  (3-hydroxy-3-methylglutaryl-CoA reductase)

Additional Information