{
  "abstract": "BackgroundCerebral palsy (CP) from perinatal hypoxic-ischaemic brain injury lacks effective therapies. Human amniotic mesenchymal stem cell-derived exosomes (hAMSC-exos) show neuroprotective potential, but their mechanisms remain unclear. This study investigated the effects and molecular pathways of hAMSC-exos in a neonatal rat CP model and an oxygen-glucose deprivation/reoxygenation (OGD/R) neuronal model.MethodshAMSC-exos were isolated and characterised. Severe CP was induced in postnatal day 21 rats by carotid ligation and hypoxia; hAMSC-exos or vehicle were given via tail vein 24 h later. Brain histology, ultrastructure, TSC1/mTOR/ULK1 pathway proteins, and apoptosis were assessed. In vitro, cortical neurons underwent OGD/R with or without exosomes; mitochondrial function (ATP, ROS, membrane potential), morphology, dynamics proteins (DRP1, FIS1, MFN1, MFN2), and PINK1/Parkin-mediated mitophagy were evaluated.ResultshAMSC-exos significantly ameliorated cortical neuronal degeneration, Nissl loss, and mitochondrial ultrastructural damage, and reduced autophagosome accumulation. They reversed CP-induced TSC1 upregulation, restored mTOR phosphorylation, and decreased ULK1 phosphorylation, correlating with fewer apoptotic neurons. In vitro, exosomes restored ATP content, reduced mitochondrial ROS, and normalised membrane potential. OGD/R caused excessive mitochondrial elongation via MFN1 upregulation; exosomes selectively downregulated MFN1 without affecting fission proteins (DRP1, FIS1). Moreover, exosomes restored impaired PINK1/Parkin-mediated mitophagy, increasing co-localisation of phospho-PINK1, phospho-Parkin, and LAMP1 with mitochondria, and rescued their phosphorylated protein levels.ConclusionhAMSC-exos protect against hypoxic-ischaemic injury through coordinated regulation of mitochondrial quality control, involving suppression of excessive TSC1/mTOR/ULK1-mediated autophagy (in vivo) and restoration of PINK1/Parkin-mediated mitophagy (in vitro), collectively preserving mitochondrial integrity and reducing neuronal apoptosis. These findings support hAMSC-exos as a promising cell-free therapeutic strategy for CP.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "Yu Zhou"
    },
    {
      "name": "Fuli Yan"
    },
    {
      "name": "Zhouzhou Li"
    },
    {
      "name": "Luna He"
    },
    {
      "name": "Jing Gao"
    },
    {
      "name": "Xuefeng Yu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0qrwxfh6ssnn7.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1965262",
  "fulltext_url": null,
  "id": "0qrwxfh6ssnn7",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1965262",
  "language": null,
  "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": [
    [
      "feed-journal",
      "medicine/pharmacology-toxicology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/0qrwxfh6ssnn7.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:20:50Z",
      "native_id": "10.3389/fphar.2026.1965262",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1965262"
    },
    {
      "first_seen": "2026-11-04T12:21:43Z",
      "native_id": "10.3389/fphar.2026.1965262",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1965262/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/pharmacology-toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Human amniotic mesenchymal stem cell-derived exosomes alleviate cerebral Palsy–Associated neuronal damage via TSC1/mTOR/ULK1 autophagy suppression and PINK1/Parkin mitophagy restoration",
  "title_text": "Human amniotic mesenchymal stem cell-derived exosomes alleviate cerebral Palsy–Associated neuronal damage via TSC1/mTOR/ULK1 autophagy suppression and PINK1/Parkin mitophagy restoration",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T00:21:25Z",
  "url": "https://research.draconitic.com/paper/0qrwxfh6ssnn7",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}