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Corticotropin-releasing hormone and brain mast cells regulate blood-brain-barrier permeability [...]

Discussion in 'Mast Cell Disorders/Mastocytosis' started by nanonug, Nov 10, 2012.

  1. nanonug

    nanonug Senior Member

    Virginia, USA
    Does this explain post-exertional malaise and neurological issues experienced by people with ME/CFS?

    J Pharmacol Exp Ther. 2002 Dec;303(3):1061-6.
    Corticotropin-releasing hormone and brain mast cells regulate blood-brain-barrier permeability induced by acute stress.

    Esposito P, Chandler N, Kandere K, Basu S, Jacobson S, Connolly R, Tutor D, Theoharides TC.

    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, New England Medical Center, Boston, Massachusetts 02111, USA.

    Stress activates the hypothalamic-pituitary-adrenal axis through release of corticotropin releasing hormone (CRH), leading to production of glucocorticoids that down-regulate immune responses. Acute stress, however, also has proinflammatory effects that seem to be mediated through the activation of mast cells. Stress and mast cells have been implicated in the pathophysiology of various inflammatory conditions, including some in the central nervous system, such as multiple sclerosis in which disruption of the blood-brain barrier (BBB) precedes clinical symptoms. We previously showed that acute restraint stress increases rat BBB permeability to intravenous 99Tc gluceptate and that administration of the "mast cell stabilizer" disodium cromoglycate (cromolyn) inhibits this effect. In this study, we show that the CRH-receptor antagonist Antalarmin blocks stress-induced 99Tc extravasation, whereas site-specific injection of CRH in the paraventricular nucleus (PVN) of the hypothalamus mimics acute stress. This latter effect is blocked by pretreatment of the PVN with cromolyn; moreover, restraint stress cannot disrupt the BBB in the diencephalon and cerebellum of W/W(v) mast cell-deficient mice. These results demonstrate that CRH and mast cells are involved in regulating BBB permeability and, possibly, brain inflammatory disorders exacerbated by acute stress.
    PMID: 12438528
    heapsreal likes this.
  2. Waverunner

    Waverunner Senior Member

    Is there any way to get a systemic effect of cromolyn? It is available as capsules, drops etc. but I read that it doesn't cross into the bloodstream.
  3. xjhuez

    xjhuez Senior Member


    According to this study - - there are many things that increase BBB permeability, including inflammation.

    I also think it's of note that histamine is "one of the few central nervous system neurotransmitters found to cause consistent blood-brain barrier opening" as I believe many of us here with methylation issues potentially have high histamine.

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