Glutamate excitotoxicity in pediatric neurological diseases evaluated with MR spectroscopy

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K08237
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Takanashi Junichi 東京女子医科大学, 医学部, 教授 (00302555)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: MRスペクトロスコピー / グルタミン酸毒性 / けいれん重積型（二相性）急性脳症（AESD） / 軽症興奮毒性型急性脳症（MEEX） / 二相性経過と遅発性拡散能低下を呈する乳児脳傷害

Outline of Final Research Achievements

Excessive intrasynaptic glutamate causes delayed neuronal damage. Magnetic resonance spectroscopy (MRS) in acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) revealed that glutamate excitotoxicity is involved in the pathology, and that N-acetylaspartate (NAA), a marker of neuronal function, is useful for predicting prognosis.
We also reported that in mild encephalopathy associated with excitotoxicity (MEEX), glutamine levels were transiently high, but NAA was normal, suggesting a broadening of the disease spectrum. We established the clinical picture of infantile traumatic brain injury with a biphasic clinical course and late reduced diffusion (TBIRD), which is similar to AESD, and revealed the involvement of excitotoxicity through MRS analysis.

Free Research Field

小児神経学

Academic Significance and Societal Importance of the Research Achievements

AESDはわが国の小児急性脳症で最多の症候群であり、60%以上で神経学的後遺症を呈する。病態は未解明であったが、MRSを用いた研究によりグルタミン酸興奮毒性が発症に関与していることが示され、脳平温療法が治療法として推奨される基盤情報となった。MEEXと合わせ興奮毒性型脳症の疾患概念を確立し得た。乳児期の頭部外傷に伴ってAESD同様に二相性の臨床経過をとることが示され、臨床医にとって重要な情報を提供し得た。