Development of vagus nerve stimulation therapy for Parkinson's disease
| Project/Area Number |
19K18430
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56010:Neurosurgery-related
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| Research Institution | Okayama University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | パーキンソン病 / 迷走神経刺激療法 / 神経保護効果 / 抗炎症効果 / 電気刺激療法 / 神経新生 / 神経保護 / 神経炎症 |
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| Outline of Research at the Start |
パーキンソン病（PD）はアルツハイマー型認知症に次いで2番目に多い神経変性疾患であり、未だ根本的治療が存在しない難病である。病初期は薬物治療が、進行期では脳深部刺激療法（DBS）が奏功するが、手術を受けることができない患者も多く存在し、低侵襲で効果の高いニューロモデュレーション治療の開発が望まれる。迷走神経刺激療法（VNS）は難治性てんかんに対する緩和的外科治療であるが、最近基礎研究でVNSが正常ラット脳の細胞外ドパミン濃度を増加させると報告された。In vivoレベルでの研究はなく、我々はPDモデルラットを用いて、VNSの効果を検討し、PDの新たな治療法を展開する。
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| Outline of Final Research Achievements |
A cuff-type silver electrode was placed in the left cervical vagus nerve and then 6-hydroxydopamine was stereotactically administered to the left striatum to create a model of Parkinson disease. VNS was performed for 14 days. The stimulation conditions are divided into 4 groups: stimulation width: 500usec, stimulation frequency: 30Hz, stimulation intensity: 0.10mA, 0.25mA, 0.50mA, 1.0mA. Result: VNS showed behavioral improvement from the 7th day with low-intensity stimulation of 0.25mA and 0.50mA, and the effect was maintained even on the 14th day. Under the same conditions, TH-positive fiber density and cell number were significantly maintained compared with the control group, and the expression numbers of inflammatory microglia and astrocytes in the same area decreased in the stimulation group. In addition, NA neurons in the locus coeruleus were retained in the stimulus group.
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| Academic Significance and Societal Importance of the Research Achievements |
迷走神経は全身に広く分布されており、VNSの正確な機序については不明点が多いのが実情である。今後は迷走神経の上行性・下行性線維をそれぞれ刺激し、炎症性サイトカイン、アセチルコリン受容体の発現動態の評価を追加で行う予定である。近年では、PDの発症と腸管炎症の関連性、腸脳相関が注目されており、腸管炎症モデルを使用した実験も病態解明に有効と考える。また、当科はPDモデルへ新規システムを使用した脊髄刺激実験も施行している。外科的な低侵襲治療の開発に向けて、複数の電気刺激実験を並行して施行する計画である。
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Report
(4 results)
Research Products
(92 results)
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[Journal Article] Vagus nerve stimulation with mild stimulation intensity exerts anti-inflammatory and neuroprotective effects in Parkinson's disease model rats2021
Author(s)
Kin I , Sasaki T , Yasuhara T , Kameda M , Agari T , Okazaki M , Hosomoto K , Okazaki Y , Yabuno S , Kawauchi S , Kuwahara K , Morimoto J , Kin K , Umakoshi M , Tomita Y , Tajiri N , Borlongan CV , Date I
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Journal Title
Biomedicines
Volume: 9(7):789
Issue: 7
Pages: 789-789
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Growth curves for intracranial volume and two-dimensional parameters for Japanese children without cranial abnormality: Toward treatment of craniosynostosis2021
Author(s)
Tomita Y , Kameda K , Senoo T , Tokuyama E , Sugahara C , Yabuno S , Okazaki Y , Kawauchi S , Hosomoto K , Sasaki T , Tasuhara T, Date I
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Journal Title
Neurologica medico-chirurgica
Volume: ー
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Long-term continuous cervical spinal cord stimulation exerts neuroprotective effects in experimental Parkinson's disease2020
Author(s)
Kuwahara K , Sasaki T , Yasuhara T , Kameda M , Okazaki Y , Hosomoto K , Kin I , Okazaki M , Yabuno S , Kawauchi S , Tomita Y , Umakoshi M , Kin K , Morimoto J , Lee J-Y , Tajiri N , Borlongan CV , Date I
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Journal Title
Frontiers in Aging Neuroscience
Volume: 16;12:164.
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cell therapy for central nervous system disorders: Current obstacles to progress2019
Author(s)
Yasuhara T , Kawauchi S , Kin K , Morimoto J , Kameda M , Sasaki T , Bonsack B , Kingsbury C , Tajiri N , Borlongan CV , Date I
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Journal Title
CNS Neuroscience & Therapeutics
Volume: ー
Issue: 6
Pages: 592-602
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Lithium counteracts depressive behavior and augments the treatment effect of selective serotonin reuptake inhibitor in treatment-resistant depressed rats2019
Author(s)
Kin K, Yasuhara T, Kawauchi S, Kameda M, Hosomoto K, Tomita Y, Umakoshi M, Kuwahara K, Kin I, Kidani N, Morimoto J, Sasaki T, Date I
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Journal Title
Brain Research
Volume: 1717
Pages: 52-59
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification of somatotopic organization and optimal stimulation site within the subthalamic nucleus for Parkinson's disease2019
Author(s)
Sasaki T , Kuwahara K , Kin I , Okazaki M , Sasada S , Shinko A , Kameda M , Yasuhara T , Agari T , Date I
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Journal Title
Operative Neurosurgery (Hagerstown, Md.)
Volume: 17(3)
Issue: 3
Pages: 239-246
DOI
Related Report
Peer Reviewed
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