{
  "abstract": "BackgroundNeuroinflammation and regulated cell death (RCD) are important components of secondary injury after acute ischemic stroke (AIS). However, the myeloid cell states involved in these processes and their spatial organization within ischemic brain tissue remain incompletely understood. This study aimed to characterize RCD-associated inflammatory myeloid remodeling by integrating clinical observations with single-cell and spatial transcriptomic analyses.MethodsWe retrospectively analyzed 367 patients with anterior-circulation AIS, comprising earlier (n = 216) and later (n = 151) admission cohorts. Clinical characteristics, inflammatory markers, early neurological deterioration (END), and 90-day functional outcomes were evaluated. Public mouse single-cell, single-nucleus, bulk, and spatial transcriptomic datasets (GSE174574 and GSE233815) were integrated to investigate RCD-associated cellular heterogeneity, myeloid-state transitions, transcriptional regulation, metabolic programs, intercellular communication, and spatial distributions.ResultsEND occurred in 51 patients (13.9%), and 127 (34.6%) experienced unfavorable 90-day functional outcomes. Unfavorable outcomes were associated with greater neurological severity and higher admission neutrophil-to-lymphocyte ratios and C-reactive protein levels. Transcriptomic analyses identified a distinct RCD-high inflammatory macrophage state characterized by coordinated expression of inflammasome/pyroptosis-associated genes (Nlrp3, Pycard, Casp1, Gsdmd, and Il1b) and phagocytic markers (Cd68, Mertk, and Ctsb). This state was concentrated at later inferred myeloid pseudotime and exhibited NF-κB/STAT-associated regulatory programs, metabolic remodeling, and extensive predicted interactions with glial and vascular cells. Spatial transcriptomic mapping revealed localized RCD-high macrophage-associated signals in post-ischemic brain tissue, with partially overlapping distributions across related myeloid states.ConclusionThis study identifies an RCD-high inflammatory macrophage state characterized by the convergence of cell-death-associated, phagocytic, and metabolic stress-response programs following cerebral ischemia. Its transcriptional characteristics, predicted intercellular interactions, and heterogeneous spatial distribution provide new insights into post-ischemic myeloid remodeling and the cellular organization of neuroinflammation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, Affiliated Hospital of Hebei University, Baoding, Hebei, China",
    "Department of Emergency Medicine, Affiliated Hospital of Hebei University, Baoding, Hebei, China",
    "Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, Hebei, China",
    "Department of Neurology, Baoding No. 1 Central Hospital, Baoding, Hebei, China",
    "Department of Rheumatology and Immunology, Baoding No. 1 Central Hospital, Baoding, Hebei, China",
    "Department of Rehabilitation Medicine, Affiliated Hospital of Hebei University, Baoding, Hebei, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Nan Jia"
    },
    {
      "affs": [
        1
      ],
      "name": "Jianqi Li"
    },
    {
      "affs": [
        2
      ],
      "name": "He Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Hongfan Huo"
    },
    {
      "affs": [
        3
      ],
      "name": "Xinxin Li"
    },
    {
      "affs": [
        4
      ],
      "name": "Yaping Yan"
    },
    {
      "affs": [
        0
      ],
      "name": "Biao Hua"
    },
    {
      "affs": [
        5
      ],
      "name": "Liang Qin"
    },
    {
      "affs": [
        0
      ],
      "name": "Li Ling"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cm9tmmz1mp16g.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1981135",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fcell.2026.1981135/full",
  "id": "cm9tmmz1mp16g",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://doi.org/10.3389/fcell.2026.1981135",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH301-705.5"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-05",
  "publisher": "Frontiers Media S.A.",
  "ris": "https://research.draconitic.com/paper/cm9tmmz1mp16g.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T14:21:22Z",
      "native_id": "036120b720344398934c76a9f82cc05c",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fcell.2026.1981135"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "journal-openalex:F13",
      "subfield": "general"
    },
    {
      "field": "biology",
      "origin": "lcc:QH301-705.5",
      "subfield": "general"
    }
  ],
  "title": "Clinical, single-cell, and spatial transcriptomic integration identifies an RCD-high inflammatory myeloid program for early neurological deterioration and outcome stratification after acute ischemic stroke",
  "title_text": "Clinical, single-cell, and spatial transcriptomic integration identifies an RCD-high inflammatory myeloid program for early neurological deterioration and outcome stratification after acute ischemic stroke",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T14:20:36Z",
  "url": "https://research.draconitic.com/paper/cm9tmmz1mp16g",
  "venue": "Frontiers in Cell and Developmental Biology",
  "versions": []
}