{
  "abstract": "Background: Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients after major surgery. It delays postoperative recovery and increases the risk of neurodegenerative disorders. CaMKIIδ is a key calcium-signaling regulator of neuronal survival and neuroinflammation, yet its functional role in POCD remains poorly understood. This study aimed to identify injury-inducible calcium-signaling genes and to characterize the association of Camk2d, the gene encoding CaMKIIδ, with POCD progression in aged rats.\n\nMethods: A POCD model was established in aged rats by sevoflurane anesthesia combined with splenectomy. Cognitive function was evaluated with the Morris water maze (MWM) and Y-maze tests. Hippocampal transcriptome profiling was performed using RNA sequencing and weighted gene co-expression network analysis (WGCNA). Key molecular and pathological alterations were validated by RT-qPCR, Western blotting, ELISA, and histological staining, and the pan-CaMKII inhibitor KN-93 was administered for functional validation. Serum inflammatory cytokines were measured in parallel to characterize peripheral-to-central inflammatory coupling.\n\nResults: Cognitive performance was worst on postoperative day 3, which was therefore identified as the critical injury window of POCD. Hippocampal CaMKIIδ, phosphorylated NF-κB (p-NF-κB), pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), and pro-apoptotic Bax were markedly upregulated, whereas anti-apoptotic Bcl-2 reached its lowest level and neuronal apoptosis peaked on day 3. KN-93 treatment downregulated CaMKIIδ expression, suppressed neuroinflammation and neuronal apoptosis, and effectively rescued cognitive impairment in POCD rats.\n\nConclusion: Camk2d upregulation is closely associated with POCD pathogenesis, paralleling hippocampal neuroinflammation and neuronal apoptosis. Pharmacological inhibition of CaMKII by KN-93 alleviates POCD, supporting CaMKII signaling as a potential therapeutic target for perioperative cognitive protection.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Anesthesiology, The First Affiliated Hospital of Shihezi University, Shihezi, China",
    "School of Medicine, Shihezi University, Shihezi, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Kaihua Wei"
    },
    {
      "affs": [
        0
      ],
      "name": "Shiwen Fan"
    },
    {
      "affs": [
        0
      ],
      "name": "Yujia Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaobin Cai"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinlei Qin"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingwen Zhai"
    },
    {
      "affs": [
        0
      ],
      "name": "Liping Xie"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4ek9qeqkp41hc.bib",
  "cited_by": 0,
  "doi": "10.3389/fnagi.2026.1975677",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696443/",
  "id": "4ek9qeqkp41hc",
  "issns": [
    "1663-4365"
  ],
  "landing_url": "https://doi.org/10.3389/fnagi.2026.1975677",
  "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",
      "Original Research"
    ],
    [
      "openalex",
      "2806|Anesthesia and Neurotoxicity Research"
    ]
  ],
  "openalex": "W7221577000",
  "pdf_url": "https://europepmc.org/articles/PMC13696443?pdf=render",
  "pmcid": "PMC13696443",
  "pmid": "42935898",
  "published": "2026-10-12",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/4ek9qeqkp41hc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:48Z",
      "native_id": "PMC13696443",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fnagi.2026.1975677"
    },
    {
      "first_seen": "2026-10-30T12:22:12Z",
      "native_id": "MED:42935898",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42935898"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2806|Anesthesia and Neurotoxicity Research",
      "subfield": "neuroscience"
    }
  ],
  "title": "Camk2d upregulation is associated with postoperative cognitive dysfunction in aged rats: pharmacological inhibition of CaMKII attenuates hippocampal neuroinflammation and neuronal apoptosis",
  "title_text": "Camk2d upregulation is associated with postoperative cognitive dysfunction in aged rats: pharmacological inhibition of CaMKII attenuates hippocampal neuroinflammation and neuronal apoptosis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:47Z",
  "url": "https://research.draconitic.com/paper/4ek9qeqkp41hc",
  "venue": "Frontiers in Aging Neuroscience",
  "versions": []
}