{
  "abstract": "Background\n\nIntracerebral hemorrhage (ICH) is a neurological disorder with high morbidity and mortality. PAR4 has been implicated in ICH and neuroinflammation.Methods\n\nThe rat model of intracerebral hemorrhage (ICH) was established by injecting collagenase into the brain. TTC staining, H&E staining, and immunofluorescence were used to evaluate the brain tissue. In vitro, rat primary microglia (RPMCs) were isolated and the rat microglial cell line HAPI and the hippocampal neuronal cell line H19-7 were cultured. RNA-seq analysis, Western blot, co-immunoprecipitation, cell immunofluorescence, RIP assay, m⁶A Dot Blot Analysis were performed to investigate the role of PAR4 and its downstream signaling pathways.Results\n\nIn the ICH rat model, treatment with the PAR4 antagonist inhibited neuronal death and reversed the M1-dominant shift of microglia. PAR4 regulated m⁶A methylation in microglia via KIAA1429-mediated recruitment of methyltransferase complexes. PAR4AP increased JAK2 mRNA m⁶A modification, mRNA and protein levels, and enhanced STAT3 protein phosphorylation. It also increased the expression of inflammatory factors and inflammasome components, with a stronger effect on AIM2 expression. PAR4AP enhanced AIM2 expression in microglial cells through mechanisms dependent on the JAK2/STAT3 signaling pathway and m⁶A modification. PAR4AP-activated microglia induce neuronal PANoptosis via exosome-mediated transfer of AIM2, promoting Pyrin-ZBP1 complex formation. In a rat model of ICH, lentivirus-delivered shRNAs targeting KIAA1429, FMR1, and AIM2, as well as PAR4 inhibition, suppressed PANoptosis in neuronal cells.Conclusion\n\nThis study provides insights into the role of PAR4 in ICH and its downstream signaling pathways, suggesting potential therapeutic targets for ICH treatment.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, PR China.",
    "Department of Neurology, Affiliated Hospital of Jiujiang University, No. 57 East Road, Xunyang District, Jiujiang City, Jiangxi Province, PR China.",
    "Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, PR China. yinm1588@163.com.",
    "Institute of Neuroscience, Nanchang University, Nanchang, 330031, Jiangxi Province, PR China. yinm1588@163.com.",
    "Jiangxi Provincial Clinical Medical Research Center for Neurological Disorders, Nanchang, 330031, Jiangxi Province, PR China. yinm1588@163.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhengyu Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Bing Bao"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinyu Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jun Min"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhiping Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Weiping Chen"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Min Yin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8w36jp6jancm9.bib",
  "cited_by": 0,
  "doi": "10.1007/s10565-026-10237-5",
  "fulltext_url": "https://europepmc.org/articles/PMC13727903",
  "id": "8w36jp6jancm9",
  "issns": [
    "0742-2091",
    "1573-6822"
  ],
  "landing_url": "https://europepmc.org/article/MED/42972199",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2728|Intracerebral and Subarachnoid Hemorrhage Research"
    ]
  ],
  "openalex": "W7172505907",
  "pdf_url": "https://europepmc.org/articles/PMC13727903?pdf=render",
  "pmcid": "PMC13727903",
  "pmid": "42972199",
  "published": "2026-08-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8w36jp6jancm9.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:49Z",
      "native_id": "MED:42972199",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42972199"
    },
    {
      "first_seen": "2026-11-06T12:23:41Z",
      "native_id": "PMC13727903",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s10565-026-10237-5"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Intracerebral and Subarachnoid Hemorrhage Research",
      "subfield": "neurology"
    }
  ],
  "title": "PAR4 exacerbates intracerebral hemorrhage by driving m6A-dependent microglial AIM2 release and neuronal PANoptosis.",
  "title_text": "PAR4 exacerbates intracerebral hemorrhage by driving m6A-dependent microglial AIM2 release and neuronal PANoptosis.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:00Z",
  "url": "https://research.draconitic.com/paper/8w36jp6jancm9",
  "venue": "Cell biology and toxicology",
  "versions": []
}