2023 Fiscal Year Final Research Report

Synaptic intoxicant and neuroprotective effects of hydrogen sulfide

Research Project

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Project/Area Number	16K11411
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Emergency medicine
Research Institution	Sapporo Medical University
Principal Investigator	Narimatsu Eichi 札幌医科大学, 医学部, 教授 (70295343)
Co-Investigator(Kenkyū-buntansha)	沢本圭悟札幌医科大学, 医学部, 助教 (10597529) 石黒雅敬札幌医科大学, 医学部, 助教 (30404586) 高橋和伸札幌医科大学, 医学部, 助教 (40530605) 高田幸昌札幌医科大学, 医学部, 助教 (70530608)
Project Period (FY)	2016-04-01 – 2024-03-31
Keywords	hippocampus / synaptic transmission / electrophysiology / EPSP / hydrogen sulfide / neuroprotection
Outline of Final Research Achievements	We investigated neuroprotective effects of hydrogen sulfide on ischemic- or excessive glutamate-induced depressions of central (hippocampal) excitatory synaptic transmissions in vitro. From the CA1 in rat hippocampal slices, orthodromically elicited population spikes (PSs) and field excitatory postsynaptic potentials (fEPSPs) at 0.1 Hz were simultaneously recorded. Hydrogen sulfide-induced synaptic depression was reversible, however, being irreversible at higher concentration. Preceding and following applications of hydrogen sulfide at lower (reversible) concentrations protects ischemic or excessive glutamate-induced synaptic depressions, however, simultaneous application of hydrogen sulfide rather deteriorates these depressions. These results indicate that hydrogen sulfide has both protective and deteriorating effects on the primary and secondary brain damages, which depend on phase of the application of hydrogen sulfide.
Free Research Field	救急医学　集中治療学　神経科学
Academic Significance and Societal Importance of the Research Achievements	本研究では，硫化物イオンが1次性および2次性中枢神経系障害に対し限定的条件下においてそれぞれ保護的あるいは増悪的に影響するという成果を得た．この保護的影響は障害前からの予防投与および障害後投与時に限定的であり，同時投与では逆に障害を増悪させた．この硫化物イオンによる中枢神経系保護の投与時期依存性の明確化は，硫化物イオンを用いた薬理学的脳保護の研究および臨床応用を進めるにあたり重要な情報であり，学術的・社会的意義がある．