Skip to main content

Table 1 Pathophysiology of venous abnormalities in multiple sclerosis and potential therapeutic strategies

From: Venous endothelial injury in central nervous system diseases

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 [4144]
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, 4547]
Hemodynamic abnormality, CCSVI PGI2, NO, EDHF Venous pressure reduction venoplasty [48, 49]
  1. 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, PGI 2 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.