Reactive pericytes in early phase are involved in glial activation and late-onset hypersusceptibility to pilocarpine-induced seizures in traumatic brain injury model mice
In this study, among neurovascular unit (NVU) cells, we focused on pericyte reactivity in mice subjected to controlled cortical impact (CCI) to understand how traumatic brain injury (TBI) causes uncoordinated crosstalk in the NVU and alters neuronal activity. Histological analyses of brain pericytes...
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| Language: | English |
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Elsevier
2021-01-01
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| Series: | Journal of Pharmacological Sciences |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861320301146 |
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| author | Kenta Sakai Fuyuko Takata Gaku Yamanaka Miho Yasunaga Kana Hashiguchi Kazuki Tominaga Kouichi Itoh Yasufumi Kataoka Atsushi Yamauchi Shinya Dohgu |
| author_facet | Kenta Sakai Fuyuko Takata Gaku Yamanaka Miho Yasunaga Kana Hashiguchi Kazuki Tominaga Kouichi Itoh Yasufumi Kataoka Atsushi Yamauchi Shinya Dohgu |
| author_sort | Kenta Sakai |
| collection | DOAJ |
| description | In this study, among neurovascular unit (NVU) cells, we focused on pericyte reactivity in mice subjected to controlled cortical impact (CCI) to understand how traumatic brain injury (TBI) causes uncoordinated crosstalk in the NVU and alters neuronal activity. Histological analyses of brain pericytes, microglia and astrocytes were performed for up to 28 days after CCI in the injured ipsilateral hippocampus. To evaluate altered neuronal activity caused by CCI, we measured seizure susceptibility to a sub-threshold dose of pilocarpine on postoperative day 7, 14, 21 and 28. Platelet-derived growth factor receptor (PDGFR) β immunoreactivity in pericytes significantly increased from 1 h to 4 days after CCI. The expression of Iba1 and GFAP, as markers of microglia and astrocytes, respectively, increased from 4 to 28 days after CCI. The severity of seizure induced by pilocarpine gradually increased, becoming significant at 28 days after CCI. Then, we treated CCI mice with an inhibitor of PDGFR signaling, imatinib, during the postoperative day 0–4 period. Imatinib lowered seizure susceptibility to pilocarpine and suppressed microglial activation in the injured hippocampus at postoperative day 28. These findings indicate that brain pericytes with rapidly increased PDGFRβ expression may drive TBI-induced dysregulation of NVU function and brain hyperexcitability. |
| first_indexed | 2024-12-20T00:33:03Z |
| format | Article |
| id | doaj.art-cc66b0bede0d4aedae7bd73d13ca81ea |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-20T00:33:03Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-cc66b0bede0d4aedae7bd73d13ca81ea2022-12-21T19:59:53ZengElsevierJournal of Pharmacological Sciences1347-86132021-01-011451155165Reactive pericytes in early phase are involved in glial activation and late-onset hypersusceptibility to pilocarpine-induced seizures in traumatic brain injury model miceKenta Sakai0Fuyuko Takata1Gaku Yamanaka2Miho Yasunaga3Kana Hashiguchi4Kazuki Tominaga5Kouichi Itoh6Yasufumi Kataoka7Atsushi Yamauchi8Shinya Dohgu9Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, 814-0180, JapanDepartment of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, 814-0180, Japan; Corresponding author. Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.Fax: +81 92 862 2699.Department of Pediatrics and Adolescent Medicine, Tokyo Medical University, Tokyo, 160-0023, JapanDepartment of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, 814-0180, JapanDepartment of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, 814-0180, JapanDepartment of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, 814-0180, JapanLaboratory for Pharmacotherapy and Experimental Neurology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Kagawa, 769-2193, JapanDepartment of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, 814-0180, JapanDepartment of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, 814-0180, JapanDepartment of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, 814-0180, JapanIn this study, among neurovascular unit (NVU) cells, we focused on pericyte reactivity in mice subjected to controlled cortical impact (CCI) to understand how traumatic brain injury (TBI) causes uncoordinated crosstalk in the NVU and alters neuronal activity. Histological analyses of brain pericytes, microglia and astrocytes were performed for up to 28 days after CCI in the injured ipsilateral hippocampus. To evaluate altered neuronal activity caused by CCI, we measured seizure susceptibility to a sub-threshold dose of pilocarpine on postoperative day 7, 14, 21 and 28. Platelet-derived growth factor receptor (PDGFR) β immunoreactivity in pericytes significantly increased from 1 h to 4 days after CCI. The expression of Iba1 and GFAP, as markers of microglia and astrocytes, respectively, increased from 4 to 28 days after CCI. The severity of seizure induced by pilocarpine gradually increased, becoming significant at 28 days after CCI. Then, we treated CCI mice with an inhibitor of PDGFR signaling, imatinib, during the postoperative day 0–4 period. Imatinib lowered seizure susceptibility to pilocarpine and suppressed microglial activation in the injured hippocampus at postoperative day 28. These findings indicate that brain pericytes with rapidly increased PDGFRβ expression may drive TBI-induced dysregulation of NVU function and brain hyperexcitability.http://www.sciencedirect.com/science/article/pii/S1347861320301146Traumatic brain injuryReactive pericytesPDGFRβImatinibMicroglia |
| spellingShingle | Kenta Sakai Fuyuko Takata Gaku Yamanaka Miho Yasunaga Kana Hashiguchi Kazuki Tominaga Kouichi Itoh Yasufumi Kataoka Atsushi Yamauchi Shinya Dohgu Reactive pericytes in early phase are involved in glial activation and late-onset hypersusceptibility to pilocarpine-induced seizures in traumatic brain injury model mice Journal of Pharmacological Sciences Traumatic brain injury Reactive pericytes PDGFRβ Imatinib Microglia |
| title | Reactive pericytes in early phase are involved in glial activation and late-onset hypersusceptibility to pilocarpine-induced seizures in traumatic brain injury model mice |
| title_full | Reactive pericytes in early phase are involved in glial activation and late-onset hypersusceptibility to pilocarpine-induced seizures in traumatic brain injury model mice |
| title_fullStr | Reactive pericytes in early phase are involved in glial activation and late-onset hypersusceptibility to pilocarpine-induced seizures in traumatic brain injury model mice |
| title_full_unstemmed | Reactive pericytes in early phase are involved in glial activation and late-onset hypersusceptibility to pilocarpine-induced seizures in traumatic brain injury model mice |
| title_short | Reactive pericytes in early phase are involved in glial activation and late-onset hypersusceptibility to pilocarpine-induced seizures in traumatic brain injury model mice |
| title_sort | reactive pericytes in early phase are involved in glial activation and late onset hypersusceptibility to pilocarpine induced seizures in traumatic brain injury model mice |
| topic | Traumatic brain injury Reactive pericytes PDGFRβ Imatinib Microglia |
| url | http://www.sciencedirect.com/science/article/pii/S1347861320301146 |
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