2023 Fiscal Year Final Research Report
Challenging the epileptogenicity of febrile seizures from pericytes, the command center for the propagation of inflammation in the brain.
| Project/Area Number |
20K17909
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 55060:Emergency medicine-related
|
|---|
| Research Institution | Tokyo Medical University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2020-04-01 – 2024-03-31
|
| Keywords | ペリサイト / 熱性けいれん / てんかん / 血液脳関門 / 血管内皮障害 / サイトカイン解析 |
|---|
| Outline of Final Research Achievements |
This study investigated the involvement of immunological mechanisms in the epileptogenicity of febrile seizures (FS), with a focus on pericytes. (A) We measured pericyte-related factors PDGFRβ/CD13/BMP and compared them with HMGB1/BDNF/VEGF associated with DAMPs, and found that PDGFRβ/HMGB1/BDNF/VEGF were significantly elevated in CNS infection and refractory epilepsy patients with neurological sequelae after FS. (B) We analyzed the differences in cytokine reactivity of peripheral blood mononuclear cells stimulated by LPS by FACS. IL-1β decreased promptly after seizure before and after seizure in complicated FS. (C) Cytokine analysis showed that PDGF-BB/VEGF/IL-1β/IL-6 were elevated in FS (especially complex type) and epilepsy groups. Pericyte-related factors move interactively with specific cytokine groups and may be involved in blood-brain barrier fragility and neuroinflammation in convulsive disorders, including FS.
|
| Free Research Field |
小児神経学
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果から，FSを含めたけいれん性疾患においてペリサイト関連因子は特定のサイトカイン群とともに血液脳関門（BBB）の脆弱性や神経炎症に関与する可能性が示唆された．けいれん発作後の病的ペリサイトはてんかんや認知機能障害へと病態を進展させる可能性がある．そのため脳神経血管ユニットおよびBBBを強化する治療選択を行うことができれば，てんかん原性防止の一助になるかもしれない．
急性期にてんかん原性を抑え込むことは長期にわたる抗てんかん薬の内服を避け，QOLの改善のみならず医療資源の抑制に寄与すると考えた．
|
