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Experimental inflammation following dural application of complete Freund’s adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage

BACKGROUND: Migraine is a paroxysmal, disabling primary headache that affects 16 % of the adult population. In spite of decades of intense research, the origin and the pathophysiology mechanisms involved are still not fully known. Although triptans and gepants provide effective relief from acute mig...

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Autores principales: Lundblad, Cornelia, Haanes, Kristian A., Grände, Gustaf, Edvinsson, Lars
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Milan 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627622/
https://www.ncbi.nlm.nih.gov/pubmed/26512021
http://dx.doi.org/10.1186/s10194-015-0575-8
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author Lundblad, Cornelia
Haanes, Kristian A.
Grände, Gustaf
Edvinsson, Lars
author_facet Lundblad, Cornelia
Haanes, Kristian A.
Grände, Gustaf
Edvinsson, Lars
author_sort Lundblad, Cornelia
collection PubMed
description BACKGROUND: Migraine is a paroxysmal, disabling primary headache that affects 16 % of the adult population. In spite of decades of intense research, the origin and the pathophysiology mechanisms involved are still not fully known. Although triptans and gepants provide effective relief from acute migraine for many patients, their site of action remains unidentified. It has been suggested that during migraine attacks the leakiness of the blood-brain barrier (BBB) is altered, increasing the passage of anti-migraine drugs. This study aimed to investigate the effect of experimental inflammation, following dural application of complete Freund’s adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage. METHODS: In order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface. Following 2, 24 or 48 h of inflammation we calculated permeability-surface area product (PS) for [(51)Cr]-EDTA in the trigeminal ganglion (TG), spinal trigeminal nucleus, cortex, periaqueductal grey and cerebellum. RESULTS: We observed that [(51)Cr]-EDTA did not pass into the central nervous system (CNS) in a major way. However, [(51)Cr]-EDTA readily passed the TG by >30 times compared to the CNS. Application of CFA or IS did not show altered transfer constants. CONCLUSIONS: With these experiments we show that dural IS/CFA triggered TG inflammation, did not increase the BBB passage, and that the TG is readily exposed to circulating molecules. The TG could provide a site of anti-migraine drug interaction with effect on the trigeminal system. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s10194-015-0575-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-46276222015-11-05 Experimental inflammation following dural application of complete Freund’s adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage Lundblad, Cornelia Haanes, Kristian A. Grände, Gustaf Edvinsson, Lars J Headache Pain Research Article BACKGROUND: Migraine is a paroxysmal, disabling primary headache that affects 16 % of the adult population. In spite of decades of intense research, the origin and the pathophysiology mechanisms involved are still not fully known. Although triptans and gepants provide effective relief from acute migraine for many patients, their site of action remains unidentified. It has been suggested that during migraine attacks the leakiness of the blood-brain barrier (BBB) is altered, increasing the passage of anti-migraine drugs. This study aimed to investigate the effect of experimental inflammation, following dural application of complete Freund’s adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage. METHODS: In order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface. Following 2, 24 or 48 h of inflammation we calculated permeability-surface area product (PS) for [(51)Cr]-EDTA in the trigeminal ganglion (TG), spinal trigeminal nucleus, cortex, periaqueductal grey and cerebellum. RESULTS: We observed that [(51)Cr]-EDTA did not pass into the central nervous system (CNS) in a major way. However, [(51)Cr]-EDTA readily passed the TG by >30 times compared to the CNS. Application of CFA or IS did not show altered transfer constants. CONCLUSIONS: With these experiments we show that dural IS/CFA triggered TG inflammation, did not increase the BBB passage, and that the TG is readily exposed to circulating molecules. The TG could provide a site of anti-migraine drug interaction with effect on the trigeminal system. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s10194-015-0575-8) contains supplementary material, which is available to authorized users. Springer Milan 2015-10-28 /pmc/articles/PMC4627622/ /pubmed/26512021 http://dx.doi.org/10.1186/s10194-015-0575-8 Text en © Lundblad et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Research Article
Lundblad, Cornelia
Haanes, Kristian A.
Grände, Gustaf
Edvinsson, Lars
Experimental inflammation following dural application of complete Freund’s adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage
title Experimental inflammation following dural application of complete Freund’s adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage
title_full Experimental inflammation following dural application of complete Freund’s adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage
title_fullStr Experimental inflammation following dural application of complete Freund’s adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage
title_full_unstemmed Experimental inflammation following dural application of complete Freund’s adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage
title_short Experimental inflammation following dural application of complete Freund’s adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage
title_sort experimental inflammation following dural application of complete freund’s adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627622/
https://www.ncbi.nlm.nih.gov/pubmed/26512021
http://dx.doi.org/10.1186/s10194-015-0575-8
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