Cerebral hypoperfusion: a new pathophysiologic concept in multiple sclerosis?

J Cereb Blood Flow Metab. 2015 Sep;35(9):1406-10. doi: 10.1038/jcbfm.2015.131. Epub 2015 Jun 24.

Abstract

The exact pathogenesis of multiple sclerosis (MS) is incompletely understood. Although auto-immune responses have an important role in the development of hallmark focal demyelinating lesions, the underlying mechanism of axonal degeneration, the other key player in MS pathology and main determinant of long-term disability, remains unclear and corresponds poorly with inflammatory disease activity. Perfusion-weighted imaging studies have demonstrated that there is a widespread cerebral hypoperfusion in patients with MS, which is present from the early beginning to more advanced disease stages. This reduced cerebral blood flow (CBF) does not seems to be secondary to loss of axonal integrity with decreased metabolic demands but appears to be mediated by elevated levels of the potent vasospastic peptide endothelin-1 in the cerebral circulation. Evidence is evolving that cerebral hypoperfusion in MS is associated with chronic hypoxia, focal lesion formation, diffuse axonal degeneration, cognitive dysfunction, and fatigue. Restoring CBF may therefore emerge as a new therapeutic target in MS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Blood Flow Velocity
  • Brain Ischemia* / metabolism
  • Brain Ischemia* / pathology
  • Brain Ischemia* / physiopathology
  • Cerebrovascular Circulation*
  • Cognition Disorders* / metabolism
  • Cognition Disorders* / pathology
  • Cognition Disorders* / physiopathology
  • Diffuse Axonal Injury* / metabolism
  • Diffuse Axonal Injury* / pathology
  • Diffuse Axonal Injury* / physiopathology
  • Endothelin-1 / metabolism*
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Multiple Sclerosis* / metabolism
  • Multiple Sclerosis* / pathology
  • Multiple Sclerosis* / physiopathology

Substances

  • Endothelin-1