FDCA Attenuates Neuronal Ferroptosis and Reduces Hemorrhagic Transformation After Ischemic Stroke with High Glucose.

Ruohan Fu, Luyang Xie, Xin Guan, Zhuangzhuang Liang, Qingsong Zhao, Zhangjian Huang, Qinfen Wu, Tao Pang

Abstract read

In one paragraph

Article in Cellular and molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Ruohan Fu *State Key Laboratory of Natural Medicines, New Drug Screening and Pharmacodynamics Evaluation Center, Center of Drug Discovery, China Pharmaceutical University, #24 Tong Jia Xiang Street, Nanjing, 210009, P.R. China.ORCID http://orcid.org/0009-0005-5777-6840

Luyang Xie *State Key Laboratory of Natural Medicines, New Drug Screening and Pharmacodynamics Evaluation Center, Center of Drug Discovery, China Pharmaceutical University, #24 Tong Jia Xiang Street, Nanjing, 210009, P.R. China.ORCID http://orcid.org/0009-0009-1254-5706

Xin GuanState Key Laboratory of Natural Medicines, New Drug Screening and Pharmacodynamics Evaluation Center, Center of Drug Discovery, China Pharmaceutical University, #24 Tong Jia Xiang Street, Nanjing, 210009, P.R. China.ORCID http://orcid.org/0000-0001-7629-0591

Zhuangzhuang LiangState Key Laboratory of Natural Medicines, New Drug Screening and Pharmacodynamics Evaluation Center, Center of Drug Discovery, China Pharmaceutical University, #24 Tong Jia Xiang Street, Nanjing, 210009, P.R. China.ORCID http://orcid.org/0000-0002-3476-8152

Qingsong ZhaoState Key Laboratory of Natural Medicines, New Drug Screening and Pharmacodynamics Evaluation Center, Center of Drug Discovery, China Pharmaceutical University, #24 Tong Jia Xiang Street, Nanjing, 210009, P.R. China.ORCID http://orcid.org/0009-0009-9835-6905

Zhangjian HuangState Key Laboratory of Natural Medicines, New Drug Screening and Pharmacodynamics Evaluation Center, Center of Drug Discovery, China Pharmaceutical University, #24 Tong Jia Xiang Street, Nanjing, 210009, P.R. China. zhangjianhuang@cpu.edu.cn.ORCID http://orcid.org/0000-0001-6409-8535

Qinfen WuDepartment of Neurology, The Second Affiliated Hospital of Xinjiang Medical University, No. 38, Nanhu East Road, Shuimogou District, Urumqi, 830054, Xinjiang, P.R. China. wqfcat@xjmu.edu.cn.ORCID http://orcid.org/0000-0003-1360-3313

Tao PangState Key Laboratory of Natural Medicines, New Drug Screening and Pharmacodynamics Evaluation Center, Center of Drug Discovery, China Pharmaceutical University, #24 Tong Jia Xiang Street, Nanjing, 210009, P.R. China. tpang@cpu.edu.cn.ORCID http://orcid.org/0000-0001-5420-2060

Funding

the National Natural Science Foundation of China 82174010Xinjiang Uygur Autonomous Region Science and Technology Support Project 2022E02123Xinjiang Uygur Autonomous Region Science and Technology Support Project 2024E02051

6 · The paper itself

Abstract

Hemorrhagic transformation (HT) is a common complication of ischemic stroke that significantly increases the rates of disability and mortality, which could be promoted by hyperglycemia as a risk factor for HT after stroke. Neuronal ferroptosis was implicated as a key contributor to neuronal death during the development of HT which currently has few effective therapies in clinic. The compound fasudil dichloroacetate (FDCA), synthesized with ROCK inhibitor fasudil (F) and PDK inhibitor dichloroacetate (DCA) was previously reported to exhibit neuroprotective effects in ischemic stroke, but whether FDCA could ameliorate HT post-stroke remains unknown. In this study, FDCA was synthesized by combining the Rho kinase inhibitor F with the PDK inhibitor DCA. Rats with acute hyperglycemia and ischemic stroke were divided into the control group, 10 mg/kg FDCA treatment group, 7.875 mg/kg F + 3.6 mg/kg DCA combination treatment group, and other relevant control groups. Our findings demonstrate that FDCA treatment significantly reduced the area of cerebral HT, HT scores, and hemoglobin content in rat brains, improved neurological function, and decreased mortality. Mechanistically, FDCA inhibited neuronal ferroptosis in peri-hematomal region by downregulating the ACSL4 protein expression and the phosphorylation levels of MYPT1 and PDH, while upregulating the GPX4 protein expression. Additionally, FDCA attenuated RSL3-induced neuronal ferroptosis in SH-SY5Y cells in vitro. These results suggest that FDCA holds promise as a potential therapeutic agent for the clinical treatment of HT following ischemic stroke.

Indexed as

1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineCerebral HemorrhageFerroptosisGlucoseIschemic StrokeNeuronsAnimalsHumansMaleNeuroprotective AgentsRatsRats, Sprague-Dawley1-(5-Isoquinolinesulfonyl)-2-MethylpiperazinefasudilGlucoseNeuroprotective AgentsDichloroacetic acidFasudilFerroptosisHemorrhagic transformationIschemic stroke

Identifiers

PMID41535628

DOI10.1007/s10571-025-01664-9

PMCPMC12873023

What Socratic holds

Textmetadata

LicenceCC BY-NC-ND

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.