Venous endothelial injury in central nervous system diseases

Jonathan S. Alexander, Leonard Prouty, Ikuo Tsunoda, Chaitanya Vijay Ganta, Alireza Minagar

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The role of the venous system in the pathogenesis of inflammatory neurological/neurodegenerative diseases remains largely unknown and underinvestigated. Aside from cerebral venous infarcts, thromboembolic events, and cerebrovascular bleeding, several inflammatory central nervous system (CNS) diseases, such as multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), and optic neuritis, appear to be associated with venous vascular dysfunction, and the neuropathologic hallmark of these diseases is a perivenous, rather than arterial, lesion. Such findings raise fundamental questions about the nature of these diseases, such as the reasons why their pathognomonic lesions do not develop around the arteries and what exactly are the roles of cerebral venous inflammation in their pathogenesis. Apart from this inflammatory-based view, a new hypothesis with more focus on the hemodynamic features of the cerebral and extracerebral venous system suggests that MS pathophysiology might be associated with the venous system that drains the CNS. Such a hypothesis, if proven correct, opens new therapeutic windows in MS and other neuroinflammatory diseases. Here, we present a comprehensive review of the pathophysiology of MS, ADEM, pseudotumor cerebri, and optic neuritis, with an emphasis on the roles of venous vascular system programming and dysfunction in their pathogenesis. We consider the fundamental differences between arterial and venous endothelium, their dissimilar responses to inflammation, and the potential theoretical contributions of venous insufficiency in the pathogenesis of neurovascular diseases.

Original languageEnglish (US)
Article number219
JournalBMC Medicine
Volume11
Issue number1
DOIs
StatePublished - Oct 11 2013
Externally publishedYes

Keywords

  • ADEM
  • CNS
  • Inflammation
  • MS
  • Venous

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'Venous endothelial injury in central nervous system diseases'. Together they form a unique fingerprint.

Cite this