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  "work": {
    "type": "RDN",
    "kind": "note",
    "key": "xie-2013",
    "id": "TAP-RDN-0062",
    "locale": "en",
    "path": "/research/xie-2013/",
    "title": "TAP reading note: Sleep drives metabolite clearance from the adult brain",
    "description": "Mouse experiments linked natural sleep and anaesthesia with extracellular space, cerebrospinal-fluid influx and tracer clearance. The study measured both influx and clearance of cortically injected radiolabelled amyloid-β and inulin; faster amyloid-β clearance during sleep provides mechanistic evidence concerning brain solute transport.",
    "rights": "© The Allostasis Project. All rights reserved. Reproduction or adaptation requires separate permission, subject to applicable legal exceptions.",
    "version": "1.0",
    "updatedAt": "2026-10-29",
    "editorial": {
      "contentType": "evidence-review",
      "reviewState": "draft",
      "reviewedAt": null,
      "reviewedVersion": null,
      "updatedAt": "2026-10-29",
      "version": "1.0",
      "byline": "team",
      "author": null,
      "reviewer": null,
      "workflow": {
        "ai": {
          "usage": "used",
          "system": "OpenAI Codex",
          "scope": "Assisted source comparison, evidence extraction and bilingual research-note preparation. The materials consulted and unresolved scientific issues are specified in each note.",
          "version": "1.0",
          "tasks": [
            "Source comparison and evidence extraction",
            "Bilingual research-note drafting and editorial comparison"
          ]
        }
      },
      "revisions": [
        {
          "date": "2026-10-29",
          "version": "1.0",
          "description": "Added the 2013 mouse study and clarified that it includes clearance as well as influx experiments."
        }
      ]
    },
    "original": {
      "id": "xie-2013",
      "title": "Sleep drives metabolite clearance from the adult brain",
      "authors": "Xie L · Kang H · Xu Q · Chen MJ · Liao Y · Thiyagarajan M · O'Donnell J · Christensen DJ · Nicholson C · Iliff JJ · Takano T · Deane R · Nedergaard M",
      "journal": "Science",
      "year": "2013",
      "url": "https://doi.org/10.1126/science.1241224",
      "doi": "10.1126/science.1241224",
      "pmid": "24136970"
    },
    "references": [
      {
        "id": "xie-2013",
        "title": "Sleep drives metabolite clearance from the adult brain",
        "authors": "Xie L · Kang H · Xu Q · Chen MJ · Liao Y · Thiyagarajan M · O'Donnell J · Christensen DJ · Nicholson C · Iliff JJ · Takano T · Deane R · Nedergaard M",
        "journal": "Science",
        "year": "2013",
        "url": "https://doi.org/10.1126/science.1241224",
        "doi": "10.1126/science.1241224",
        "pmid": "24136970"
      }
    ],
    "sections": [
      {
        "id": "finding",
        "title": "What the study found",
        "paragraphs": [
          "Mouse experiments linked natural sleep and anaesthesia with extracellular space, cerebrospinal-fluid influx and tracer clearance. The study measured both influx and clearance of cortically injected radiolabelled amyloid-β and inulin; faster amyloid-β clearance during sleep provides mechanistic evidence concerning brain solute transport."
        ]
      },
      {
        "id": "limits",
        "title": "Scope & limitations",
        "paragraphs": [
          "Awake, naturally sleeping and anaesthetised mice, with experiment-specific subsamples and repeated measurements.",
          "Invasive procedures, state, timing, anaesthetic and tracer molecules matter. Injection routes, molecules and estimation differ from Miao and colleagues' 2024 study, so one result cannot simply replace the other. Mouse mechanisms do not directly quantify human catch-up-sleep benefits."
        ]
      },
      {
        "id": "sample",
        "title": "Population & sample",
        "paragraphs": [
          "Awake, naturally sleeping and anaesthetised mice, with experiment-specific subsamples and repeated measurements."
        ]
      },
      {
        "id": "exposure",
        "title": "Exposure or intervention",
        "paragraphs": [
          "Natural sleep/wake and ketamine–xylazine anaesthesia, with CSF tracing, TMA extracellular-space measurements, amyloid-β/inulin clearance and adrenergic manipulation."
        ]
      },
      {
        "id": "outcomes",
        "title": "Outcomes",
        "paragraphs": [
          "Extracellular volume fraction, tracer influx and clearance, interpreted separately by experiment."
        ]
      },
      {
        "id": "duration",
        "title": "Time frame",
        "paragraphs": [
          "Short-term state and tracer experiments; no human clinical follow-up."
        ]
      },
      {
        "id": "funding",
        "title": "Research funding",
        "paragraphs": [
          "NIH/NINDS NS078167, NS078304 and NS028642."
        ]
      },
      {
        "id": "conflicts",
        "title": "Research conflicts of interest",
        "paragraphs": [
          "A complete separate competing-interest statement has not been located."
        ]
      },
      {
        "id": "basis",
        "title": "Reading scope",
        "paragraphs": [
          "The body results and Figures 1–4 captions were read through. Key supplementary methods remain unavailable, leaving experiment-specific denominators and procedural details to be checked."
        ],
        "links": [
          {
            "label": "Full text in PubMed Central",
            "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3880190/"
          },
          {
            "label": "Compare the related original study and its methods",
            "url": "https://doi.org/10.1038/s41593-024-01638-y"
          }
        ]
      }
    ]
  }
}
