{
"papers": [
{
"n": null,
"doi": "10.1126/scitranslmed.3003748",
"value": "~70%",
"method": "intracortical tracer injection + two-photon imaging",
"metric": "Reduction in interstitial solute clearance in AQP4-knockout mice",
"n_analyzed": null,
"ci_or_error": null,
"text_access": "abstract_only",
"n_definition": "mice genotype groups",
"scope_region": "mouse cortex and brain parenchyma",
"study_system": "mouse Aqp4-/- vs wild-type",
"taxonomic_level": "whole-brain clearance",
"scope_population": "interstitial-fluid solute tracers",
"value_source_sentence": "Animals lacking the water channel aquaporin-4 (AQP4) in astrocytes exhibit slowed CSF influx through this system and a ~70% reduction in interstitial solute clearance, suggesting that the bulk fluid flow between these anatomical influx and efflux routes is supported by astrocytic water transport.",
"experimental_conditions": "in vivo 2-photon imaging of CSF tracers"
},
{
"n": 6,
"doi": "10.1126/science.1241224",
"value": "+67% (13.6% awake → 22.7% anesthesia)",
"method": "real-time TMA+ iontophoresis, two-photon imaging",
"metric": "Increase in interstitial volume fraction (awake vs anesthetized/sleep)",
"n_analyzed": null,
"ci_or_error": "±1.6% awake; ±1.3% anesth",
"text_access": "fulltext",
"n_definition": "mice measured with real-time iontophoresis",
"scope_region": "mouse cortex (in vivo)",
"study_system": "adult mouse cortex (in vivo)",
"taxonomic_level": "regional tissue measurement",
"scope_population": "ECS volume fraction",
"value_source_sentence": "This approach, which eliminated interanimal variability in electrode placement and TMA calibration, showed that anesthesia consistently increased the interstitial space volume fraction by >60%, from 13.6 ± 1.6% for awake mice to 22.7 ± 1.3% in the same mice after anesthesia.",
"experimental_conditions": "awake vs natural-sleep vs anesthetized"
},
{
"n": null,
"doi": "10.1002/ana.24271",
"value": "40% decrease",
"method": "radiotracer clearance assay + in vivo fluorescence microscopy",
"metric": "Reduction in amyloid-β clearance (old vs young mice)",
"n_analyzed": null,
"ci_or_error": null,
"text_access": "abstract_only",
"n_definition": "mice per age group",
"scope_region": "mouse cortex (in vivo)",
"study_system": "young (2-3 mo), middle-aged (10-12 mo), old (18-20 mo) C57BL/6 mice",
"taxonomic_level": "whole-brain clearance",
"scope_population": "interstitial amyloid-β",
"value_source_sentence": "Relative to the young, clearance of intraparenchymally injected amyloid-β was impaired by 40% in the old mice.",
"experimental_conditions": "intraparenchymal radiotracer clearance"
},
{
"n": null,
"doi": "10.1523/jneurosci.3020-14.2014",
"value": "~60% reduction",
"method": "in vivo tracer imaging of CSF-ISF exchange",
"metric": "Reduction in glymphatic pathway function after traumatic brain injury",
"n_analyzed": null,
"ci_or_error": null,
"text_access": "abstract_only",
"n_definition": "mice per condition",
"scope_region": "mouse cortex",
"study_system": "mouse, controlled cortical impact TBI",
"taxonomic_level": "whole-brain clearance",
"scope_population": "CSF-ISF tracer clearance",
"value_source_sentence": "After TBI, glymphatic pathway function was reduced by ∼60%, with this impairment persisting for at least 1 month post injury.",
"experimental_conditions": "TBI vs sham"
}
],
"comparison_id": "glymphatic-aqp4-clearance-magnitude",
"comparison_name": "Magnitude of AQP4/glymphatic dependence of interstitial solute clearance across perturbations",
"comparison_type": "convergent evidence",
"what_it_reveals": "AQP4 deletion (~70% clearance loss; Iliff 2012), TBI (~60% reduction; Iliff 2014 JNeurosci), aging (~40% Aβ clearance loss; Kress 2014), and sleep state (~60% ECS volume swing; Xie 2013) each independently converge on glymphatic flow being a major, quantitatively dominant clearance route — while also revealing substantial residual clearance in AQP4-null conditions, setting the stage for later replication challenges.",
"homogeneity_check": {
"caveats": [
"Metrics differ: Iliff 2012 and Iliff 2014 TBI report tracer clearance reduction; Kress 2014 reports Aβ-specific clearance; Xie 2013 reports ECS volume fraction",
"Different tracers (fluorescent dextrans, radiolabeled Aβ) and different imaging modalities (in vivo 2P, radiotracer, real-time iontophoresis)",
"All measurements are on mouse cortex but perturbations span genetic, traumatic, aging, and state-dependent axes"
],
"n_definition_uniform": "false",
"scope_region_uniform": "true",
"taxonomic_level_uniform": "false",
"scope_population_uniform": "false"
},
"suggested_plot_type": "grouped bar"
}