MAP Kinase Pathways in Brain Endothelial Cells and Crosstalk with Pericytes and Astrocytes Mediate Contrast-Induced Blood–Brain Barrier Disruption
Neurointervention with contrast media (CM) has rapidly increased, but the impact of CM extravasation and the related side effects remain controversial. This study investigated the effect of CM on blood–brain barrier (BBB) integrity. We established in vitro BBB models using primary cultures of rat BB...
| Published in: | Pharmaceutics |
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2021-08-01
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| author | Yuki Matsunaga Shinsuke Nakagawa Yoichi Morofuji Shinya Dohgu Daisuke Watanabe Nobutaka Horie Tsuyoshi Izumo Masami Niwa Fruzsina R. Walter Ana Raquel Santa-Maria Maria A. Deli Takayuki Matsuo |
| author_facet | Yuki Matsunaga Shinsuke Nakagawa Yoichi Morofuji Shinya Dohgu Daisuke Watanabe Nobutaka Horie Tsuyoshi Izumo Masami Niwa Fruzsina R. Walter Ana Raquel Santa-Maria Maria A. Deli Takayuki Matsuo |
| author_sort | Yuki Matsunaga |
| collection | DOAJ |
| container_title | Pharmaceutics |
| description | Neurointervention with contrast media (CM) has rapidly increased, but the impact of CM extravasation and the related side effects remain controversial. This study investigated the effect of CM on blood–brain barrier (BBB) integrity. We established in vitro BBB models using primary cultures of rat BBB-related cells. To assess the effects of CM on BBB functions, we evaluated transendothelial electrical resistance, permeability, and tight junction (TJ) protein expression using immunohistochemistry (IHC) and Western blotting. To investigate the mechanism of iopamidol-induced barrier dysfunction, the role of mitogen-activated protein (MAP) kinases in brain endothelial cells was examined. We assessed the effect of conditioned medium derived from astrocytes and pericytes under iopamidol treatment. Short-term iopamidol exposure on the luminal side induced transient, while on the abluminal side caused persistent BBB dysfunction. IHC and immunoblotting revealed CM decreased the expression of TJ proteins. Iopamidol-induced barrier dysfunction was improved via the regulation of MAP kinase pathways. Conditioned medium from CM-exposed pericytes or astrocytes lacks the ability to enhance barrier function. CM may cause BBB dysfunction. MAP kinase pathways in brain endothelial cells and the interactions of astrocytes and pericytes mediate iopamidol-induced barrier dysfunction. CM extravasation may have negative effects on clinical outcomes in patients. |
| format | Article |
| id | doaj-art-d7b82985cc3b4e2fb156a5cdee2a4270 |
| institution | Directory of Open Access Journals |
| issn | 1999-4923 |
| language | English |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| spelling | doaj-art-d7b82985cc3b4e2fb156a5cdee2a42702025-08-20T00:00:20ZengMDPI AGPharmaceutics1999-49232021-08-01138127210.3390/pharmaceutics13081272MAP Kinase Pathways in Brain Endothelial Cells and Crosstalk with Pericytes and Astrocytes Mediate Contrast-Induced Blood–Brain Barrier DisruptionYuki Matsunaga0Shinsuke Nakagawa1Yoichi Morofuji2Shinya Dohgu3Daisuke Watanabe4Nobutaka Horie5Tsuyoshi Izumo6Masami Niwa7Fruzsina R. Walter8Ana Raquel Santa-Maria9Maria A. Deli10Takayuki Matsuo11Department of Neurosurgery, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanDepartment of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, JapanDepartment of Neurosurgery, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanDepartment of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, JapanBBB Laboratory, PharmaCo-Cell Company Ltd., Dai-ichi-senshu bldg. 2nd Floor, 6-19 Chitose-machi, Nagasaki 852-8135, JapanDepartment of Neurosurgery, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanDepartment of Neurosurgery, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanBBB Laboratory, PharmaCo-Cell Company Ltd., Dai-ichi-senshu bldg. 2nd Floor, 6-19 Chitose-machi, Nagasaki 852-8135, JapanBiological Barriers Research Group, Institute of Biophysics, Biological Research Centre, 6726 Szeged, HungaryBiological Barriers Research Group, Institute of Biophysics, Biological Research Centre, 6726 Szeged, HungaryBiological Barriers Research Group, Institute of Biophysics, Biological Research Centre, 6726 Szeged, HungaryDepartment of Neurosurgery, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, JapanNeurointervention with contrast media (CM) has rapidly increased, but the impact of CM extravasation and the related side effects remain controversial. This study investigated the effect of CM on blood–brain barrier (BBB) integrity. We established in vitro BBB models using primary cultures of rat BBB-related cells. To assess the effects of CM on BBB functions, we evaluated transendothelial electrical resistance, permeability, and tight junction (TJ) protein expression using immunohistochemistry (IHC) and Western blotting. To investigate the mechanism of iopamidol-induced barrier dysfunction, the role of mitogen-activated protein (MAP) kinases in brain endothelial cells was examined. We assessed the effect of conditioned medium derived from astrocytes and pericytes under iopamidol treatment. Short-term iopamidol exposure on the luminal side induced transient, while on the abluminal side caused persistent BBB dysfunction. IHC and immunoblotting revealed CM decreased the expression of TJ proteins. Iopamidol-induced barrier dysfunction was improved via the regulation of MAP kinase pathways. Conditioned medium from CM-exposed pericytes or astrocytes lacks the ability to enhance barrier function. CM may cause BBB dysfunction. MAP kinase pathways in brain endothelial cells and the interactions of astrocytes and pericytes mediate iopamidol-induced barrier dysfunction. CM extravasation may have negative effects on clinical outcomes in patients.https://www.mdpi.com/1999-4923/13/8/1272blood–brain barriercontrast mediaiopamidolMAP kinasepericytesastrocytes |
| spellingShingle | Yuki Matsunaga Shinsuke Nakagawa Yoichi Morofuji Shinya Dohgu Daisuke Watanabe Nobutaka Horie Tsuyoshi Izumo Masami Niwa Fruzsina R. Walter Ana Raquel Santa-Maria Maria A. Deli Takayuki Matsuo MAP Kinase Pathways in Brain Endothelial Cells and Crosstalk with Pericytes and Astrocytes Mediate Contrast-Induced Blood–Brain Barrier Disruption blood–brain barrier contrast media iopamidol MAP kinase pericytes astrocytes |
| title | MAP Kinase Pathways in Brain Endothelial Cells and Crosstalk with Pericytes and Astrocytes Mediate Contrast-Induced Blood–Brain Barrier Disruption |
| title_full | MAP Kinase Pathways in Brain Endothelial Cells and Crosstalk with Pericytes and Astrocytes Mediate Contrast-Induced Blood–Brain Barrier Disruption |
| title_fullStr | MAP Kinase Pathways in Brain Endothelial Cells and Crosstalk with Pericytes and Astrocytes Mediate Contrast-Induced Blood–Brain Barrier Disruption |
| title_full_unstemmed | MAP Kinase Pathways in Brain Endothelial Cells and Crosstalk with Pericytes and Astrocytes Mediate Contrast-Induced Blood–Brain Barrier Disruption |
| title_short | MAP Kinase Pathways in Brain Endothelial Cells and Crosstalk with Pericytes and Astrocytes Mediate Contrast-Induced Blood–Brain Barrier Disruption |
| title_sort | map kinase pathways in brain endothelial cells and crosstalk with pericytes and astrocytes mediate contrast induced blood brain barrier disruption |
| topic | blood–brain barrier contrast media iopamidol MAP kinase pericytes astrocytes |
| url | https://www.mdpi.com/1999-4923/13/8/1272 |
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