Venous endothelial injury in central nervous system diseases

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, 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.

ISSN: 1741-7015