Table 1

Pathophysiology of venous abnormalities in multiple sclerosis and potential therapeutic strategies
Pathophysiology Involved molecules Potential intervention Potential treatments References
Higher venous endothelial responses to inflammation Cytokines, chemokines, adhesion molecules, occludin Induction of MKP-1, protection against shear stress responses Dexamethasone [16,39]
Altered hemodynamic signaling in venous inflammation KLF2, KLF4, eNOS, VCAM-1, PAI-I, TNF-α Activation of KLF2 and KLF4 Statin drugs, HDAC inhibitors (for example, trichostatin-A) [8,30,36,40]
BBB dysregulation NMDA receptor, MMP-8, MMP-9, p38 MAPK MMP inhibitor, p38 MAPK inhibitor Doxycycline, minocycline, SB 239063 [41-44]
Venous remodeling Collagens, iron, TGF-β1, p38 MAPK, VEGF, TIMP, MMP p38 MAPK inhibitor, TGF modifier, angiotensin antagonist, anti-angiogenic drug, MMP inhibitor Drugs (dilamapimod, avotermin, candesartan, bevacizumab, cavtratin, doxycycline, desferrioxamine) [8,45-47]
Hemodynamic abnormality, CCSVI PGI2, NO, EDHF Venous pressure reduction venoplasty [48,49]

Abbreviations:BBB blood-brain barrier, CCSVI chronic cerebrospinal venous insufficiency, EDHF endothelium-derived hyperpolarizing factor, eNOS Endothelial nitric oxide synthase, HDAC histone deacetylase, KLF Krueppel-like factor, MAPK mitogen-activated protein kinase, MKP mitogen-activated protein kinase phosphatase, MMP matrix metalloproteinase, MS multiple sclerosis, NMDA N-methyl-D-aspartate, NO nitrous oxide, PAI plasminogen activator inhibitor, PGI2 prostaglandin I2 (prostacyclin), TGF transforming growth factor, TIMP tissue inhibitor of metalloproteinase, TNF tumor necrosis factor, VCAM vascular cell adhesion molecule, VEGF Vascular endothelial growth factor.

Alexander et al.

Alexander et al. BMC Medicine 2013 11:219   doi:10.1186/1741-7015-11-219

Open Data