A synthetic heparin-mimicking polyanionic compound inhibits central nervous system inflammation.

Abstract	The immunomodulating capacity of heparin led us to test the effect of the synthetic heparin-mimicking and low anticoagulant compound RG-13577 on the course of experimental autoimmune encephalomyelitis (EAE) and central nervous system (CNS) inflammation. EAE was induced in SJL mice by inoculation with whole mouse spinal cord homogenate. RG-13577, delivered intraperitoneally, inhibited the clinical signs of acute EAE and markedly ameliorated inflammation in the spinal cord, primarily by inhibiting heparanase activity in lymphocytes and astrocytes and thus impairing lymphocyte traffic. RG-13577 treatment was effective when started on day of disease induction or day 7 after induction. The low molecular weight heparin, enoxaparin, tested under the same conditions, exerted only a minor insignificant inhibitory effect. RG-13577 also inhibited the tyrosine phosphorylation of several proteins, particularly Erk1 and Erk2 of the MAP kinase signaling pathways associated with inflammation and cell proliferation. RG-13577 blocked the activity of sPLA(2) and inhibited CNS PGE(2) production both in vivo and in vitro.
Authors	Michal Irony-Tur-Sinai, Israel Vlodavsky, Shmuel A Ben-Sasson, Florence Pinto, Camille Sicsic, Talma Brenner
Journal	Journal of the neurological sciences (J Neurol Sci) Vol. 206 Issue 1 Pg. 49-57 (Jan 15 2003) ISSN: 0022-510X [Print] Netherlands
PMID	12480085 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Anticoagulants DNA Primers Phenoxyacetates Polymers 2-(4-hydroxyphenoxy)acetic acid-formaldehyde polymer Phosphotyrosine Heparin heparanase Glucuronidase Dinoprostone
Topics	Animals Anticoagulants (pharmacology) Brain (metabolism) Central Nervous System (drug effects, physiopathology) DNA Primers Dinoprostone (metabolism) Encephalomyelitis, Autoimmune, Experimental (physiopathology) Female Glucuronidase (genetics) Heparin (chemistry, pharmacology, physiology) Inflammation (prevention & control) Mice Mice, Inbred Strains Phenoxyacetates (pharmacology) Phosphorylation Phosphotyrosine (metabolism) Polymers (pharmacology) Spinal Cord (drug effects, physiopathology)

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