Interaction of inflammation, thrombosis, aspirin and enoxaparin in CNS experimental antiphospholipid syndrome

• Main Authors: David Tanne, Aviva Katzav, Orit Beilin, Nikolaos C. Grigoriadis, Miri Blank, Chaim G. Pick, Philipp von Landenberg, Yehuda Shoenfeld, Joab Chapman
• Format: Article
• Language: English
• Published: Elsevier 2008-04-01
• Series: Neurobiology of Disease
• Subjects: Animal models; Anticoagulation; Aspirin; Antiphospholipid syndrome; Behavior; Inflammation
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996107002707

Experimental antiphospholipid syndrome (eAPS) induced by immunization with β2-glycoprotein I (β2-GPI) causes behavioral hyperactivity. We assessed the role of thrombotic and inflammatory perivascular factors and standard APS therapies for CNS manifestations. Groups of mice (n=10 per group) were immunized once with β2-GPI (eAPS) or adjuvant (controls) and treated daily from 1 month after immunization with either sham injections, aspirin (1.2 mg/kg) or enoxaparin (1 mg/kg) for 3 months. Serum antiphospholipid antibodies (aPL) and brain levels of tissue necrosis factor-α (TNF-α) and prostaglandin E (PGE) were then measured by ELISA and thrombin inhibitors by immunoblot. Behavioral hyperactivity was assessed by the staircase test. The eAPS mice had higher levels of aPL than adjuvant immunized controls. Inflammatory markers were found to be twofold higher and intrinsic brain thrombin inhibitors 50% lower in eAPS brains compared to controls. aPL titers were unaffected by treatment. Both aspirin and enoxaparin normalized brain concentrations of PGE and TNF-α and elevated thrombin inhibitors, the latter effect being more pronounced for enoxaparin. The increased activity and rearing exploratory behavior in eAPS (138.6±13.6 and 141.9±13.9% of controls, respectively) were attenuated significantly more by treatment with enoxaparin (91.5±12.3 and 95.0±9.8%) than by aspirin (167.0±18.4 and 114.7±13.1%, p<0.01, ANOVA). Together, these results demonstrate that eAPS is associated with significant brain inflammation and thrombosis that are well treated with both standard therapies for human APS. Enoxaparin attenuates behavior better than aspirin possibly by reducing thrombosis or stabilization of the blood brain barrier, suggesting an advantage for similar drugs in CNS APS.