Acute stress increases permeability of the blood-brain-barrier through activation of brain mast cells

Brain Res. 2001 Jan 5;888(1):117-127. doi: 10.1016/s0006-8993(00)03026-2.


Disruption of the blood-brain-barrier (BBB) is important in the pathophysiology of various inflammatory conditions of the central nervous system (CNS), such as multiple sclerosis (MS), in which breakdown of the BBB precedes any clinical or pathological findings. There is some evidence that relapsing-remitting MS attacks may be correlated with certain types of acute stressful episodes. Stress typically activates the hypothalamic-pituitary-adrenal (HPA) axis through the release of corticotropin releasing hormone (CRH), leading to production of glucocorticoids that down regulate immune responses. However, acute stress also has pro-inflammatory effects that appear to be mediated through activation of mast cells. Here we show that acute stress by immobilization increased permeability of rat BBB to intravenous 99Technetium gluceptate (99Tc). This effect was statistically significant in the diencephalon and the cerebellum, while it was absent in the cerebral cortex where there are not mast cells. Immobilization stress also induced activation of mast cells in diencephalon, the site where most mast cells are found in the rat brain. Both BBB permeability and mast cell activation were inhibited by the 'mast cell stabilizer' disodium cromoglycate (cromolyn). These results expand the pathophysiology of mast cells and implicate them in CNS disorders, that may possibly be induced or exacerbated by stress.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adrenocorticotropic Hormone / metabolism
  • Animals
  • Anti-Asthmatic Agents / pharmacology
  • Blood-Brain Barrier / immunology*
  • Coloring Agents / pharmacokinetics
  • Cromolyn Sodium / pharmacology
  • Diencephalon / blood supply
  • Diencephalon / immunology*
  • Diencephalon / metabolism
  • Encephalitis / immunology
  • Encephalitis / metabolism
  • Evans Blue / pharmacokinetics
  • Male
  • Mast Cells / drug effects
  • Mast Cells / immunology*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Restraint, Physical
  • Stress, Physiological / immunology*
  • Stress, Physiological / metabolism*
  • Sugar Acids / pharmacokinetics*
  • Technetium / pharmacokinetics
  • Tolonium Chloride


  • Anti-Asthmatic Agents
  • Coloring Agents
  • Sugar Acids
  • Tolonium Chloride
  • Evans Blue
  • Technetium
  • Adrenocorticotropic Hormone
  • alpha-glucoheptonic acid
  • Cromolyn Sodium