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

Disruption of the blood-brain-barrier (BBB) is important in the pathophysio logy of various inflammatory conditions of the central nervous system (CNS) , such as multiple sclerosis (MS), in which breakdown of the BBB precedes a ny clinical or pathological findings. There is some evidence that relapsing -remitting MS attacks may be correlated with certain types of acute stressf ul episodes. Stress typically activates the hypothalamic-pituitary-adrenal (HPA) axis through the release of corticotropin releasing hormone (CRH). le ading 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 b y immobilization increased permeability of rat BBB to intravenous (99)Techn etium gluceptate (Tc-99). This effect was: statistically significant in the diencephalon and the cerebellum, while it was absent in the cerebral corte x where there are not mast cells. Immobilization stress also induced activa tion of mast cells in diencephalon. the site where most mast cells are foun d in the rat brain. Both BBB permeability and mast cell activation were inh ibited by the 'mast cell stabilizer' disodium cromoglycate (cromolyn). Thes e results expand the pathophysiology of mast cells and implicate them in CN S disorders, that may possibly be induced or exacerbated by stress. (C) 200 1 Elsevier Science B.V. All rights reserved.