The role of pericytes in the development of epileptogenesis after traumatic brain injury
| Project/Area Number |
18K06712
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47040:Pharmacology-related
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| Research Institution | Fukuoka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
古賀 允久 福岡大学, 薬学部, 准教授 (60570801)
片岡 泰文 福岡大学, 薬学部, 教授 (70136513)
岩尾 卓朗 福岡大学, 薬学部, 助教 (30846374)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | ペリサイト / 頭部外傷 / てんかん / アストロサイト / ミクログリア / 神経易興奮性 / グルタミン酸 / 脳ペリサイト / PDGFRβ / PDGFR |
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| Outline of Final Research Achievements |
Traumatic brain injury TBI produces the secondary damages including late-onset epilepsy. To understand how TBI causes an uncoordinated crosstalk in the neurovascular unit (NVU) and neuronal hyperexcitability, we focused on pericyte reactivity in the NVU cell properties in TBI mice. PDGFRβ immunoreactivities in pericytes were significantly increased in the early phase (up to 4 days after TBI). Microglial and astrocyte activations were found during a period from 4 to 28 days after TBI. The severity of seizure induced by pilocarpine gradually increased, becoming significant at 28 days after TBI. Then, treatment of imatinib, an inhibitor of PDGFR signaling, during the early phase lowered seizure susceptibility to pilocarpine, suppressed microglial activation and decreased expression of the astrocytic glutamate transporter. These findings indicate that brain pericytes with rapidly increased PDGFRβ expression may drive TBI-induced dysregulation of NVU function and brain hyperexcitability.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでの頭部外傷後の遅発性てんかん研究では、脳神経活動異常、BBB機能障害、グリア細胞活性化についてそれぞれ個別で議論されてきたため、その発症機構の全貌を捉えることが困難であったと推測される。本研究は、頭部外傷後のペリサイト活性化がneurovascular unitの不調和を牽引することを明らかにし、遅発性てんかんの病態形成過程を段階的かつ複合的に捉えることを可能とした点に学術的意義がある。抗てんかん薬に抵抗性を示す遅発性てんかんの治療法は、未だ確立されていない。ペリサイトを本疾患の新規治療標的として提案することは、新たな治療薬開発の隘路を切り開く可能性があり、社会的意義は大きい。
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Report
(4 results)
Research Products
(9 results)
