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Endothelial histamine H1 receptor signaling reduces blood-brain barrier permeability...

Discussion in 'Other Health News and Research' started by nanonug, Nov 3, 2012.

  1. nanonug

    nanonug Senior Member

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    Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18967-72. Epub 2010 Oct 18.
    Endothelial histamine H1 receptor signaling reduces blood-brain barrier permeability and susceptibility to autoimmune encephalomyelitis.

    Lu C, Diehl SA, Noubade R, Ledoux J, Nelson MT, Spach K, Zachary JF, Blankenhorn EP, Teuscher C.
    Source

    Department of Medicine, University of Vermont, Burlington, VT 05405, USA.
    Abstract

    Disruption of the blood-brain barrier (BBB) underlies the development of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis. Environmental factors, such as Bordetella pertussis, are thought to sensitize central endothelium to biogenic amines like histamine, thereby leading to increased BBB permeability. B. pertussis-induced histamine sensitization (Bphs) is a monogenic intermediate phenotype of EAE controlled by histamine H(1) receptor (Hrh1/H(1)R). Here, we transgenically overexpressed H(1)R in endothelial cells of Hrh1-KO (H(1)RKO) mice to test the role of endothelial H(1)R directly in Bphs and EAE. Unexpectedly, transgenic H(1)RKO mice expressing endothelial H(1)R under control of the von Willebrand factor promoter (H(1)RKO-vWF(H1R) Tg) were Bphs-resistant. Moreover, H(1)RKO-vWF(H1R) Tg mice exhibited decreased BBB permeability and enhanced protection from EAE compared with H(1)RKO mice. Thus, contrary to prevailing assumptions, our results show that endothelial H(1)R expression reduces BBB permeability, suggesting that endothelial H(1)R signaling may be important in the maintenance of cerebrovascular integrity.

    PMID: 20956310
     
  2. nanonug

    nanonug Senior Member

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    Virginia, USA

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