Effect of stress on brain inflammation and multiple sclerosis

Autoimmun Rev. 2013 Aug;12(10):947-53. doi: 10.1016/j.autrev.2013.02.006. Epub 2013 Mar 26.


Substantial evidence indicates that stress can precipitate or worsen symptoms of inflammation in general and more specifically in multiple sclerosis (MS), a demyelinating, autoimmune disease characterized by inflammation of the central nervous system (CNS). However, the mechanism of how stress affects MS is not well understood. We reviewed publications in PubMed since 1995 and propose that neuropeptides secreted under stress, such as corticotropin releasing hormone (CRH) and neurotensin (NT), activate microglia and mast cells to release inflammatory molecules. These lead to maturation and activation of T17 autoimmune cells, disruption of the blood-brain barrier (BBB) and T cell entry into the CNS, thus promoting brain inflammation and contributing to MS pathology. Reduction of stress and inhibition of these processes by select flavonoids could provide novel therapeutic approaches.

Keywords: Blood–brain barrier; Corticotropin-releasing hormone; Flavonoids; Inflammation; Mast cells; Microglia; Multiple sclerosis; Neuropeptides; Neurotensin; Stress.

Publication types

  • Review

MeSH terms

  • Animals
  • Encephalitis / drug therapy
  • Encephalitis / immunology
  • Encephalitis / pathology
  • Encephalitis / psychology
  • Humans
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology*
  • Multiple Sclerosis / psychology*
  • Neuropeptides / metabolism
  • Stress, Psychological*


  • Neuropeptides