Corticotropin-Releasing Hormone and Brain Mast Cells Regulate Blood-Brain-Barrier Permeability Induced by Acute Stress
Abstract
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.
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Both aging and stress weaken the integrity and function of the GI barrier and negatively affect BBB permeability, potentially accelerating inflammaging.
“Both aging and stress weaken the integrity and function of the GI barrier (Kelly et al., 2016;Thevaranjan et al., 2017) and negatively affect BBB permeability (Esposito et al., 2002;Montagne et al., 2015) potentially accelerating inflammaging.”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Esposito et al., 2002
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Cites
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“For instance, histamine and interleukin-6 can stimulate CRH release (Kjaer et al., 1998), and interleukin-6 has been shown to be a CRH-independent activator of the HPA axis (Bethin et al., 2000).”
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Research works printed but not linked: 2
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- Authors
- Esposito, P., Chandler, N., Kandere, K., Basu, S., Jacobson, S., Connolly, R., Tutor, D., & Theoharides, T. C.
- Affiliations
- Tufts University (US)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 303
- Issue
- 3
- Pages
- 1061-1066
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2102197505
- Cited by
- 252
- References
- 2
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 5 · 2023: 11 · 2022: 7 · 2021: 8 · 2020: 9 · 2019: 13 · 2018: 14 · 2017: 13 · 2016: 17 · 2015: 10 · 2014: 11 · 2013: 20 · 2012: 9
- FWCI
- 5.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS28326)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Keywords
- corticotropin-releasing factor, mast cells, blood-brain barrier permeability, acute stress, restraint stress, antalarmin, disodium cromoglycate, paraventricular nucleus, hypothalamic-pituitary-adrenal axis, neuroinflammation, multiple sclerosis, glucocorticoids
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Corticotropin-Releasing Hormone, Male, Mast Cells, Mice, Inbred C57BL, Permeability, Restraint, Physical, Stress, Physiological, Rats, Sprague-Dawley, Receptors, Corticotropin-Releasing Hormone, Mice, Knockout, Mice, Rats
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