Elucidation of pathophysiology of iNPH by dynamics analysis of water molecule

• Project/Area Number: 16K15643
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Niigata University
• Principal Investigator: Suzuki Yuji 新潟大学, 脳研究所, 准教授 (90529851)
• Co-Investigator(Kenkyū-buntansha): 藤井 幸彦 新潟大学, 脳研究所, 教授 (40283014) ; 中村 亨弥 新潟大学, 研究推進機構, 助教 (70377208) ; 山田 謙一 新潟大学, 脳研究所, 准教授 (70436773)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: iNPH / 水PET / Glymphatic System / アクアポリン / 正常圧水頭症 / PET / 水動態 / glymphatic system / 特発性正常圧水頭症 / PET画像 / アクアポリンPET / 脳神経疾患 / 神経画像診断学 / ＰＥＴ

Outline of Final Research Achievements

The purpose of this study is to directly evaluate the dynamics of water molecules in CNS in idiopathic normal pressure hydrocephalus (iNPH) for elucidating the pathophysiology. In recent years, attention has focused on cerebrospinal fluid regulatory mechanisms via the Glymphatic System including Interstitial flow, which can also be called the lymphatic system of the brain for the production and absorption of cerebrospinal fluid. We analyze the dynamics of water molecules from the analysis method using PET that it is deeply involved in iNPH showed a clear reduction in cortex-to-ventricular flow, and shunt surgery proved to improve the flow.

Academic Significance and Societal Importance of the Research Achievements

今回の研究で、iNPHの病態に水の動態が大きく関与していることが示唆され、手術などの治療の効果判定や手術時期に関する重要な情報を得ることが期待できる。さらにこの結果は、従来の脈絡叢を中心とした髄液コントロールのメカニズム以外に、Glymphatic Systemによる脳髄液のコントロールシステムが存在することを示唆するものである。
今回我々が提唱した脳内の水の動態を観察可能とする新たなる解析方法は、今後更なる研究により、iNPHのみならずGlymphatic Systemが関与する様々な疾患の病態解明に繋がることが期待される。

Research Products

• [Journal Article] Developmental abnormalities of the brain exposed to childhood maltreatment detected by diffusion tensor imaging. (2019)
  • Author(s): Yamada K, Suzuki Y, Okuyama M, Watanabe M, Nakada T
  • Journal Title: Neurological Research Volume: 41 Issue: 1 Pages: 19-25
  • DOI: 10.1080/01616412.2018.1522413
  • Peer Reviewed
• [Journal Article] Visualizing the Distribution of Matrix Metalloproteinases in Ischemic Brain Using In Vivo 19F-Magnetic Resonance Spectroscopic Imaging (2019)
  • Author(s): Huber Vincent J.、Igarashi Hironaka、Ueki Satoshi、Terumitsu-Tsujita Mika、Nito Chikako、Ohno Ken、Suzuki Yuji、Itoh Kosuke、Kwee Ingrid L.、Nakada Tsutomu
  • Journal Title: Contrast Media & Molecular Imaging Volume: 2019 Pages: 1-8
  • DOI: 10.1155/2019/8908943
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A case of atraumatic tetanus developed initially with worsening headache in a woman regularly cared for chronic headache at an outpatient clinic (2019)
  • Author(s): Tobinaga Masanobu、Suzuki Yuji、Nakajima Takashi
  • Journal Title: Clinical Case Reports Volume: 7 Issue: 3 Pages: 486-490
  • DOI: 10.1002/ccr3.2024
  • Peer Reviewed / Open Access
• [Journal Article] Age-related increase in GABAA receptor distribution in the prefrontal cortex (2019)
  • Author(s): Tobinaga Masanobu、Suzuki Yuji、Fujinaka Hidehiko、Ozawa Tetsuo、Nakajima Takashi
  • Journal Title: Journal of Clinical Neuroscience Volume: ー Pages: 106-110
  • DOI: 10.1016/j.jocn.2019.03.044
  • Peer Reviewed / Open Access
• [Journal Article] Glymphatic systemの機能画像 (2019)
  • Author(s): 鈴木雄治
  • Journal Title: Clinical Neuroscience Volume: 37 Pages: 46-48
• [Journal Article] 3DAC PROPELLER: An overly underused powerful MRI modality (2018)
  • Author(s): Nakada T, Suzuki K, Suzuki Y. Nakada K, Kwee IL
  • Journal Title: Anatomy Physiol Biochem Int J Volume: ４ Pages: 555626-555626
  • Peer Reviewed / Open Access
• [Journal Article] Advances and Challenges in Assessing 2-Hydroxyglutarate in Gliomas by Magnetic Resonance Spectroscopy: A Short Review. (2018)
  • Author(s): Natsumeda M, Igarashi H, Motohashi K, Suzuki Y, Ohkubo M, Okamoto K, Watanabe M, Nakada T, Fujii Y
  • Journal Title: Neuropsychiatry Volume: ８ Pages: 1831-8
  • Peer Reviewed / Open Access
• [Journal Article] Aquaporin PET differentiates between grade III and IV human astrocytoma. (2018)
  • Author(s): Suzuki Y, Nakamura Y, Yamada K, Kurabe S, Okamoto K, Aoki H, Kitaura H, Kakita A, Fujii Y, Huber VJ, Igarashi H, Kwee IL, Nakada T
  • Journal Title: Neurosurgery Volume: 印刷中 Issue: 6 Pages: 842-846
  • DOI: 10.1093/neuros/nyx314
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Abnormal Distribution of GABAA Receptors in Brain of Duchenne Muscular Dystrophy Patients. (2017)
  • Author(s): Suzuki Y, Higuchi S, Aida I, Nakajima T, Nakada T
  • Journal Title: Muscle Nerve Volume: Apr;55(4) Issue: 4 Pages: 591-595
  • DOI: 10.1002/mus.25383
  • Peer Reviewed
• [Journal Article] Maturational decrease of glutamate in the human cerebral cortex from childhood to young adulthood: a 1H-MR spectroscopy study. (2017)
  • Author(s): Shimizu M, Suzuki Y, Yamada K, Ueki S, Watanabe M, Igarashi H, Nakada T.
  • Journal Title: Pediatr Res Volume: 82 Issue: 5 Pages: 749-752
  • DOI: 10.1038/pr.2017.101
  • Peer Reviewed
• [Journal Article] Magnetic Resonance Imaging of Neurotransmitter-Related Molecules (2017)
  • Author(s): Igarashi Hironaka、Ueki Satoshi、Ohno Ken、Ohkubo Masaki、Suzuki Yuji
  • Journal Title: Journal of Nippon Medical School Volume: 84 Issue: 4 Pages: 160-164
  • DOI: 10.1272/jnms.84.160
  • NAID: 130006140098
  • ISSN: 1345-4676, 1347-3409
  • Peer Reviewed / Open Access
• [Journal Article] Aquaporin-4 Functionality and Virchow-Robin Space Water Dynamics: Physiological Model for Neurovascular Coupling and Glymphatic Flow (2017)
  • Author(s): Nakada Tsutomu、Kwee Ingrid、Igarashi Hironaka、Suzuki Yuji
  • Journal Title: Int J Mol Sci. Volume: 18 Issue: 8 Pages: 1798-1798
  • DOI: 10.3390/ijms18081798
  • Peer Reviewed / Open Access
• [Journal Article] MRI characteristics of the glia limitans externa: A 7T study. (2017)
  • Author(s): Suzuki K, Yamada K, Nakada K, Suzuki Y, Watanabe M, Kwee IL, Nakada T
  • Journal Title: Magn Reson Imaging Volume: 44 Pages: 140-145
  • DOI: 10.1016/j.mri.2017.08.012
  • Peer Reviewed
• [Journal Article] Slow accumulations of neural activities in multiple cortical regions precede self-initiation of movement: an event-related fMRI study (2017)
  • Author(s): Sakata H, Itoh K, Suzuki Y, Nakamura K, Watanabe M, Igarashi H, Nakada T
  • Journal Title: eNEURO Volume: Oct 30;4(5)
  • Peer Reviewed / Open Access
• [Journal Article] Maturational decrease of glutamate in the human cerebral cortex from childhood to young adulthood: A 1H-MR spectroscopy study (2017)
  • Author(s): Shimizu M, Suzuki Y, Yamada K, Ueki S, Watanabe M, Igarashi H, Nakada T
  • Journal Title: Pediatr Res Volume: 27 Issue: 1 Pages: 29-32
  • DOI: 10.1111/jon.12380
  • Peer Reviewed
• [Presentation] Relationship between reduction of water influx into CSF and senile plaque formation (β-amyloid) (2017)
  • Author(s): Yuji Suzuki
  • Organizer: Society for Neuroscience
  • Int'l Joint Research