PMID- 37695500 OWN - NLM STAT- Publisher LR - 20230928 IS - 2299-5684 (Electronic) IS - 1734-1140 (Linking) VI - 75 IP - 5 DP - 2023 Oct TI - Transient plasticity response is regulated by histone deacetylase inhibitor in oxygen-glucose deprivation condition. PG - 1200-1210 LID - 10.1007/s43440-023-00525-w [doi] AB - BACKGROUND: The pathological form of synaptic plasticity, ischemic long-term potentiation (iLTP), induced by oxygen and glucose deprivation (OGD), is implicated in the acute phase of stroke with the potentiation of N-methyl-D-aspartate receptor (NMDAR). While there has been widespread attention on the excitatory system, a recent study reported that gamma-aminobutyric acid (GABA)ergic system is also involved in iLTP. Valproic acid (VPA), a histone deacetylase inhibitor, protects against ischemic damage. However, whether VPA regulates early phase plasticity in ischemic stroke remains unknown. The present study aims to investigate the potential role and mechanism of VPA in ischemic stroke. METHODS: A brief exposure of OGD on the hippocampal slices and the induction of photothrombotic ischemia (PTI) were used as ex vivo and in vivo models of ischemic stroke, respectively. RESULTS: Using extracellular recordings, iLTP was induced in the hippocampal Schaffer collateral pathway following OGD exposure. VPA treatment abolished hippocampal iLTP via GABA(A) receptor enhancement and extracellular signal-regulated kinase (ERK) phosphorylation. Administration of VPA reduced brain infarct volume and motor dysfunction in mice with PTI. Moreover, VPA protected against ischemic injury by upregulating the GABAergic system and ERK phosphorylation, as well as by reducing of matrix metalloproteinase in a PTI-induced ischemic stroke model. CONCLUSIONS: Together, this study revealed the protection of VPA in ex vivo OGD-induced pathological form of neuroplasticity and in vivo PTI-induced brain damage and motor dysfunction through rescuing GABAergic deficiency and the pathological hallmarks of ischemia. CI - (c) 2023. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences. FAU - Chu, Ming-Chia AU - Chu MC AD - Department and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Mao, Wei-Chang AU - Mao WC AD - Department of Psychiatry, Cheng-Hsin General Hospital, Taipei, Taiwan. FAU - Wu, Han-Fang AU - Wu HF AD - Department of Optometry, MacKay Medical College, New Taipei City, Taiwan. FAU - Chang, Yun-Chi AU - Chang YC AD - Department and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Lu, Ting-I AU - Lu TI AD - Department and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Lee, Chi-Wei AU - Lee CW AD - Department and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Chung, Yueh-Jung AU - Chung YJ AD - Department and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Hsieh, Tsung-Han AU - Hsieh TH AD - Department and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Chang, Hsun-Shuo AU - Chang HS AD - School of Pharmacy, College of Pharmacy, Kaoshiung Medical University, Kaoshiung, Taiwan. FAU - Chen, Yih-Fung AU - Chen YF AD - School of Pharmacy, College of Pharmacy, Kaoshiung Medical University, Kaoshiung, Taiwan. AD - Graduate Institute of Natural Products, College of Pharmacy, Kaoshiung Medical University, Kaoshiung, Taiwan. FAU - Lin, Chia-Hsien AU - Lin CH AD - Department of Health Industry Management, Kainan University, Taoyuan, Taiwan. FAU - Tang, Chih-Wei AU - Tang CW AD - Department of Neurology, Far Eastern Memorial Hospital, New Taipei City, Taiwan. jay331@gmail.com. FAU - Lin, Hui-Ching AU - Lin HC AUID- ORCID: 0000-0002-1639-9293 AD - Department and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. hclin7@nycu.edu.tw. AD - Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan. hclin7@nycu.edu.tw. AD - Ph.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical University and National Health Research Institute, Taipei, Taiwan. hclin7@nycu.edu.tw. LA - eng GR - NSTC 111-2811-B-A49A-043/National Science and Technology Council/ GR - NSTC 111-2320-B-A49-008/National Science and Technology Council/ GR - NSTC 111-2320-B-A49-037/National Science and Technology Council/ GR - MOST111-2811-B-A49A-004/National Science and Technology Council/ GR - MOST 110-2320-B-A49A-503/National Science and Technology Council/ GR - MOST 110-2628-B-A49A-504/National Science and Technology Council/ GR - MOST 109-2628-B-010-003/National Science and Technology Council/ GR - MOST 108-2628-B-010-004/National Science and Technology Council/ GR - CY10711/Cheng Hsin/Yang Ming Joint Research Program/ GR - CY10811/Cheng Hsin/Yang Ming Joint Research Program/ GR - CY10914/Cheng Hsin/Yang Ming Joint Research Program/ GR - #NYCU-FEMH 112DN12/National Yang Ming Chiao Tung University-Far Eastern Memorial Hospital Joint Research Program/ GR - 108BRC-B503/Brain Research Center, National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan/ GR - 109BRC-B503/Brain Research Center, National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan/ GR - 110BRC-B503/Brain Research Center, National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan/ GR - 111W32503/Brain Research Center, National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan/ GR - NYCUKMU-111-I008/Kaohsiung Medical University-National Yang Ming Chiao Tung University Joint Research Program, Taiwan/ PT - Journal Article DEP - 20230911 PL - Switzerland TA - Pharmacol Rep JT - Pharmacological reports : PR JID - 101234999 SB - IM OTO - NOTNLM OT - GABAergic system OT - Hippocampus OT - Histone deacetylase inhibitor OT - Ischemic long-term potentiation EDAT- 2023/09/11 12:42 MHDA- 2023/09/11 12:42 CRDT- 2023/09/11 11:14 PHST- 2023/06/01 00:00 [received] PHST- 2023/08/25 00:00 [accepted] PHST- 2023/08/25 00:00 [revised] PHST- 2023/09/11 12:42 [pubmed] PHST- 2023/09/11 12:42 [medline] PHST- 2023/09/11 11:14 [entrez] AID - 10.1007/s43440-023-00525-w [pii] AID - 10.1007/s43440-023-00525-w [doi] PST - ppublish SO - Pharmacol Rep. 2023 Oct;75(5):1200-1210. doi: 10.1007/s43440-023-00525-w. Epub 2023 Sep 11.