551. Acute stress increases permeability of the blood-brain-barrier through activation of brain mast cells.
- Author
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Esposito P, Gheorghe D, Kandere K, Pang X, Connolly R, Jacobson S, and Theoharides TC
- Subjects
- Acute Disease, Adrenocorticotropic Hormone metabolism, Animals, Anti-Asthmatic Agents pharmacology, Coloring Agents pharmacokinetics, Cromolyn Sodium pharmacology, Diencephalon blood supply, Diencephalon metabolism, Encephalitis immunology, Encephalitis metabolism, Evans Blue pharmacokinetics, Male, Mast Cells drug effects, Multiple Sclerosis immunology, Multiple Sclerosis metabolism, Rats, Rats, Sprague-Dawley, Restraint, Physical, Technetium pharmacokinetics, Tolonium Chloride, Blood-Brain Barrier immunology, Diencephalon immunology, Mast Cells immunology, Stress, Physiological immunology, Stress, Physiological metabolism, Sugar Acids pharmacokinetics
- Abstract
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.
- Published
- 2001
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