{
  "abstract": "Aims:: Ferroptosis, an iron-dependent form of regulated cell death, contributes to neuronal injury after ischemic stroke. Because our previous cancer-cell screens identified ataxia-telangiectasia mutated (ATM) kinase, as a ferroptosis regulator, we investigated whether ATM inhibition protects neural tissue after ischemic stroke and examined determinants of therapeutic response.\n\nMethods:: ATM inhibitors, including the brain-penetrant clinical compound AZD1390, were evaluated in cultured cancer and neuronal cells, oxygen-glucose-deprived rat and mouse brain slices, and permanent middle cerebral artery occlusion models using multiple inbred and Rabep2-genotype mouse strains. Cell viability, cytotoxicity, lipid peroxidation, ferroptosis-associated markers, infarct volume, and collateral vessel density were assessed. Topical AZD1390 was also tested in mice with impaired collateral networks.\n\nResults:: ATM inhibition reduced ferroptosis-associated lipid oxidative injury and protected neurons in multiple preclinical stroke models. AZD1390 decreased lipid peroxidation and neuronal death, and reduced infarct volume in B6/J and B6/NJ mice, but not in BALB mice. Treatment efficacy varied among strains and was correlated with collateral vascular density. Systemic AZD1390 was likewise ineffective in Rabep2-knockout mice with deficient collateral networks. Early topical administration also reduced infarct volume in mice with limited collateral networks; however, differences in treatment timing and route preclude direct attribution to improved local drug delivery.\n\nConclusion:: ATM inhibition may attenuate ferroptosis-associated neuronal injury after ischemic stroke, while collateral vascular anatomy may influence therapeutic response. These findings support further mechanistic and translational evaluation of ferroptosis-targeting strategies in stroke.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27705, USA.",
    "Duke Center for Genomic and Computational Biology, Duke University, Durham, NC 27705, USA.",
    "Department of Radiation Oncology, Duke University School of Medicine, Durham, NC 27705, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Han Kyu Lee"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Chao-Chieh Lin"
    },
    {
      "affs": [
        2
      ],
      "name": "Denise E. Dunn"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yubin Chen"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ssu-Yu Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Douglas A. Marchuk"
    },
    {
      "affs": [
        2
      ],
      "name": "Scott R. Floyd"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jen-Tsan Chi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dszgp5sg4etj8.bib",
  "cited_by": 0,
  "doi": "10.70401/fos.2026.0046",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13730210/",
  "id": "dszgp5sg4etj8",
  "issns": [],
  "landing_url": "https://doi.org/10.70401/fos.2026.0046",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1306|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7221129006",
  "pdf_url": "https://oss.sciexplor.com/manuscript/906/publish/FOS_202607.pdf",
  "pmcid": "PMC13730210",
  "pmid": "42979564",
  "published": "2026-09-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dszgp5sg4etj8.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T12:20:56Z",
      "native_id": "PMC13730210",
      "source": "pmc",
      "url": "https://doi.org/10.70401/fos.2026.0046"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Ferroptosis and cancer prognosis",
      "subfield": "oncology"
    }
  ],
  "title": "ATM inhibition attenuates ferroptosis-associated injury and reduces infarct volume in experimental stroke",
  "title_text": "ATM inhibition attenuates ferroptosis-associated injury and reduces infarct volume in experimental stroke",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T12:20:56Z",
  "url": "https://research.draconitic.com/paper/dszgp5sg4etj8",
  "venue": "Ferroptosis and oxidative stress",
  "versions": []
}