The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index; 16 of the 27 sources its claims cite were checked for support.
Sleep Drives Metabolite Clearance from the Adult Brain
Open accessAbstract
Taking Out the Trash: The purpose of sleep remains mysterious. Using state-of-the-art in vivo two-photon imaging to directly compare two arousal states in the same mouse, Xie et al. (p. 373 ; see the Perspective by Herculano-Houzel ) found that metabolic waste products of neural activity were cleared out of the sleeping brain at a faster rate than during the awake state. This finding suggests a mechanistic explanation for how sleep serves a restorative function, in addition to its well-described effects on memory consolidation.
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Claims the paper makes
21 Own result · 11 Own interpretation · 4 Supported · 4 Partly supported · 4 No full text of the sources · 3 Supported so far · 1 Couldn’t confirm · 1 Own method · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The interstitial concentration of Aβ is higher in awake than in sleeping rodents and humans”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
- Not checked — no full text of the sourcecites [15] Bateman RJ Nat Med 12 856 861 2006 16799555 PMC2983090 source
- Partly supportedcites [16] Kang JE Science 326 1005 1007 2009 19779148 PMC2789838 sourceExperimental — accuracy not yet measured
The paper reports that rodent interstitial-fluid Aβ levels correlate positively with time awake and negatively with time asleep (passage 1, labeled Abstract). In humans, however, it measured Aβ in cerebrospinal fluid, not interstitial fluid, and reported a diurnal fluctuation rather than a direct awake-versus-asleep comparison (passage 5, labeled Abstract). (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Deletion of AQP4 channels reduces clearance of exogenous Aβ by 65%”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
- Partly supportedcites [12] Iliff JJ Sci Transl Med 4 147ra111 2012 PMC3551275 22896675 sourceExperimental — accuracy not yet measured
The Results section (“AQP4 facilitates the para-vascular clearance of interstitial amyloid β”; page unavailable) reports reduced clearance of injected Aβ in Aqp4-null mice compared with wild-type controls. It gives the reduction as approximately 55%, not 65%. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“cerebrospinal fluid (CSF) recirculates through the brain, interchanging with interstitial fluid (ISF) and removing interstitial proteins, including Aβ (12, 13).”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
- Supportedcites [12] Iliff JJ Sci Transl Med 4 147ra111 2012 PMC3551275 22896675 source
The Discussion describes CSF entering the brain interstitium, followed by ISF clearance along draining veins, and identifies this flow as a contributor to clearing interstitial solutes, likely including soluble Aβ1–40. The Results also report that a portion of Aβ in CSF may recirculate through the brain. These findings come from experiments in mice. (LLM, conf=0.92)
- Supportedcites [13] Iliff JJ J Clin Invest 123 1299 1309 2013 23434588 PMC3582150 source
The Introduction (p. 1) states that subarachnoid CSF recirculates through the brain parenchyma, exchanges with ISF, and facilitates clearance of interstitial solutes including soluble amyloid β. The paper attributes the amyloid-clearance finding to its authors’ earlier study, but reports and relies on that finding here. (LLM, conf=0.93)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Proteins linked to neurodegenerative diseases, including β-amyloid (Aβ) (8), α-synuclein (9), and tau (10), are present in the interstitial space surrounding cells of the brain.”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
- Not checked — no full text of the sourcecites [8] Cirrito JR Neuron 48 913 922 2005 16364896 source
- Supportedcites [9] Larson ME J Neurosci 32 10253 10266 2012 22836259 PMC3425439 source
Citation (9) is attached to α-synuclein, not to the separate claims about β-amyloid or tau. The Results section (‘Segregation of brain protein pools’) says α-synuclein was detected in an extracellular fraction and reports evidence that it is secreted into brain interstitial fluid. (LLM, conf=0.92)
- Supportedcites [10] Yamada K J Neurosci 31 13110 13117 2011 21917794 PMC4299126 source
Citation (10) is attached to tau, not to β-amyloid or α-synuclein. The Results section, “Full-length tau is present in ISF” (page unavailable), reports detecting tau in brain interstitial fluid from both wild-type and P301S transgenic mice. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Influx of CSF is in part driven by arterial pulse waves that propel the movement of CSF inward along periarterial spaces (12).”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
- Supportedcites [12] Iliff JJ Sci Transl Med 4 147ra111 2012 PMC3551275 22896675 source
The Results section reports CSF entering the brain along arteries and describes rapid para-arterial flow into the parenchyma as driven by arterial pulsation. The Discussion qualifies this mechanism as likely, consistent with the claim’s ‘in part driven’ wording. Page numbers are not provided in our copy. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“suggesting that convective movement of ISF is a substantial contributor to the removal of interstitial waste products and other products of cellular activity (12).”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
- Supportedcites [12] Iliff JJ Sci Transl Med 4 147ra111 2012 PMC3551275 22896675 source
The Discussion states that interstitial bulk flow is a critical contributor to clearing interstitial solutes from the brain. The Results also identify bulk ISF flow, rather than diffusion, as responsible for clearing interstitially delivered tracers. (LLM, conf=0.91)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“TMA recordings showed that inhibition of adrenergic signaling in cortex increased the interstitial volume fraction from 14.3 ± 5.2% to 22.6 ± 1.2% (n = 4 to 8 mice, P < 0.01, t test).”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
plaindirectn = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In sleeping mice, a robust influx of the fluorescent CSF tracer was noted along periarterial spaces, in the subpial regions, and in the brain parenchyma”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Periarterial and parenchymal tracer influx was reduced by ~95% in awake as compared with sleeping mice during the 30-min imaging session”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
plaindirectn = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Aβ was cleared twofold faster in the sleeping mice as compared with the awake mice (n = 23 to 29 mice, P < 0.05, ANOVA with Bonferroni test)”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
plaindirectn = 23- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 8
- It may state two separate claims as one. 12
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In particular, locus coeruleus–derived noradrenergic signaling appears critical for driving cortical networks into the awake state of processing (26, 27).”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
- Partly supportedcites [26] Carter ME Nat Neurosci 13 1526 1533 2010 21037585 PMC3174240 sourceExperimental — accuracy not yet measured
The Results (page not available) report that stimulating locus coeruleus neurons caused immediate sleep-to-wake transitions and changes in cortical EEG in mice, supporting a role in driving the cortex toward an awake state. The Discussion (page not available) says the locus coeruleus is sufficient for these transitions but not necessary for them; the study also does not directly assess cortical processing. Thus, calling its signaling critical for driving that processing overstates the evidence. (LLM, conf=0.86)
- Supportedcites [27] Constantinople CM Bruno RM Neuron 69 1061 1068 2011 21435553 PMC3069934 source
The Introduction states that wakefulness changed cortical processing in rat barrel cortex through direct noradrenergic modulation and concludes that arousal-related brain states act via the locus coeruleus–noradrenergic system. The Results section, “Norepinephrine is critical for awake Vm,” further reports that noradrenergic receptor blockade and an ipsilateral locus coeruleus lesion prevented sustained depolarization. (LLM, conf=0.93)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“In peripheral tissues, such as kidney and heart, noradrenaline regulates the activity of membrane transporters and channels that control cell volume (28).”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
- Could not verifycites [28] O’Donnell J Zeppenfeld D McConnell E Pena S Nedergaard M Neurochem Res 37 2496 2512 2012 22717696 PMC3548657 sourceExperimental — accuracy not yet measured
The astrocyte β-adrenergic-receptors section discusses regulation of Na+/K+-ATPase and potassium clearance in the brain, not cell-volume control in peripheral tissues. Searches for kidney, heart, cell volume, and peripheral transporters found no passage in our copy addressing the attributed claim; page numbers were not available. (LLM, conf=0.72)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“These pathways were named the glymphatic system on the basis of their dependence on astrocytic aquaporin-4 (AQP4) water channels and the adoption of functions homologous to peripheral lymphatic removal of interstitial metabolic byproducts (14).”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
- Supportedcites [14] Nedergaard M Science 340 1529 1530 2013 23812703 PMC3749839 source
The Abstract says the pathway was named the “glymphatic system” for its dependence on glial water channels and its clearance function similar to that of the peripheral lymphatic system. It also identifies astrocytic AQP4 channels as facilitating flow and describes the pathway carrying waste products out of brain interstitial fluid. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Other reports have shown that the interstitial volume is ~19% in anesthetized young mice but declines to ~13% in aged mice (22).”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
- Partly supportedcites [22] Syková E Proc Natl Acad Sci USA 102 479 484 2005 15630088 PMC544312 sourceExperimental — accuracy not yet measured
Table 1 (Results; page not available) reports an extracellular-space volume fraction of 19.9% in 6–8-month-old control females and 13.2% in 17–25-month-old control females; Materials and Methods says the animals were anesthetized. The claim omits the restriction to control females: aged control males had a value of 16.1%, while aged APP23 mice showed an increase rather than a decline. (LLM, conf=0.89)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Several degradation products of cellular activity, such as Aβ oligomers and amyloid depositions, have adverse effects on synaptic transmission (30) and cytosolic Ca2+ concentrations (31) and can trigger irreversible neuronal injury (32).”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
- Not checked — no full text of the sourcecites [30] Parameshwaran K Dhanasekaran M Suppiramaniam V Exp Neurol 210 7 13 2008 18053990 source
- Supportedcites [31] Kuchibhotla KV Neuron 59 214 225 2008 18667150 PMC2578820 source
Citation (31) is attached to the claim about cytosolic Ca2+ concentrations, not the separate claims about synaptic transmission or irreversible injury. The Discussion reports that mutant APP processing and plaque deposition induce calcium overload in the studied Alzheimer’s disease mouse models; the Introduction also describes pathological increases in intracellular Ca2+ associated with amyloid-beta aggregates. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [32] Mattson MP Ann N Y Acad Sci 747 50 76 1994 7847692 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“NE triggers rapid changes in neural activity (27, 28), which in turn can modulate the volume of the interstitial space volume (29).”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
- Supportedcites [27] Constantinople CM Bruno RM Neuron 69 1061 1068 2011 21435553 PMC3069934 source
The Results section (“Norepinephrine is critical for awake Vm”; page unavailable) reports that blocking NE receptors changes cortical activity during wakefulness, and the Discussion describes NE’s powerful effects on cortical dynamics. The Results section (“Wakefulness alters cortical dynamics”; page unavailable) describes changes around awakening. This source supports the NE–neural-activity clause; the separate claim about interstitial-space volume is attributed to citation 29, not this paper. (LLM, conf=0.86)
- Supportedcites [28] O’Donnell J Zeppenfeld D McConnell E Pena S Nedergaard M Neurochem Res 37 2496 2512 2012 22717696 PMC3548657 source
The source supports the first clause, for which citations (27, 28) are given: its Introduction describes NE-mediated phasic firing as a mechanism of rapid reorientation and says NE can alter cortical responses. The interstitial-space clause has a separate citation (29) and is not attributed to this source in the citing sentence. Page numbers are unavailable in our copy. (LLM, conf=0.89)
- Not checked — no full text of the sourcecites [29] McBain CJ Traynelis SF Dingledine R Science 249 674 677 1990 2382142 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Microdialysis samples of the interstitial fluid showed that the NE concentration did not increase in trained mice during restraining but that NE, as expected, fell after administration of ketamine/xylazine”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Interstitial volume was significantly greater than in awake littermates exposed to vehicle (aCSF) (P < 0.01) but comparable with the interstitial volume in sleeping or anesthetized mice (P = 0.77 and P = 0.95, respectively, t test)”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
plainn = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“CSF tracer influx into the brain was largely absent and only slowly gained access to the superficial cortical layers”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our analysis indicates that the cortical interstitial space increases by more than 60% during sleep, resulting in efficient convective clearance of Aβ and other compounds (Figs. 2 and 3).”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Collectively, these observations support the notion that influx of CSF tracers is suppressed in awake mice as a result of contraction of the interstitial space: The smaller space during wakefulness increases tissue resistance to interstitial fluid flux and inward movement of CSF.”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“fatal familial or sporadic insomnia is a progressively worsening state of sleeplessness that leads to dementia and death within months or years (7).”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
- Not checked — no full text of the sourcecites [7] Montagna P Gambetti P Cortelli P Lugaresi E Lancet Neurol 2 167 176 2003 12849238 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These analyses suggest that adrenergic signaling plays an important role in modulating not only cortical neuronal activity but also the volume of the interstitial space.”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
hedgedconditionaln = 4- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Arousal is driven by the concerted release of neuromodulators (25).”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
- Not checked — no full text of the sourcecites [25] Steriade M McCormick DA Sejnowski TJ Science 262 679 685 1993 8235588 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Recordings obtained 300 μm below the cortical surface did not differ significantly from those obtained at 150 μm, suggesting that preparation of the cranial window was not associated with tissue injury (n = 6 mice, P > 0.4, t test)”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
hedgedn = 6- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“continuous sleep deprivation kills rodents and flies within a period of days to weeks (5, 6).”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Sleep deprivation reduces learning, impairs performance in cognitive tests, prolongs reaction time, and is a common cause of seizures (3, 4).”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The observation that anesthesia increases glymphatic influx and efflux (Figs. 1 and 3), suggests that it is not circadian rhythm but rather the sleep-wake state itself that determines the volume of the interstitial space and therefore the efficiency of glymphatic solute clearance.”
§ Sleep Drives Metabolite Clearance from the Adult Brain > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The brain lacks a conventional lymphatic system.
“Yet despite its high metabolic rate and the fragility of neurons to toxic waste products, the brain lacks a conventional lymphatic system.”
The paper relies on this without support.
The convective exchange of CSF and ISF is organized around the cerebral vasculature, with CSF influx around arteries, whereas ISF exits along veins.
“The convective exchange of CSF and ISF is organized around the cerebral vasculature, with CSF influx around arteries, whereas ISF exits along veins.”
The paper relies on this without support.
Sleep serves a vital function.
“The conservation of sleep across all animal species suggests that sleep serves a vital function.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This was the discovery of the brain's glymphatic system, showing that sleep involves the brain-wide flushing of metabolites with cerebral spinal fluid.28”
From The overfitted brain: Dreams evolved to assist generalization (2021) · cites this paper as [28]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This led to the theory that sleep, especially during slow wave activity, had the goal of waste clearance and this is at least partly behind sleep's restorative aspect.”
From The overfitted brain: Dreams evolved to assist generalization (2021) · cites this paper as [28]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For example, transport studies using radiolabeled and unlabeled Alzheimer's A 𝛃 peptide have shown that under physiological conditions, the perivascular ISF flow contributes to 15-20% of A 𝛃 clearance from the mouse brain (58, 535, 659), whereas 8085% is removed by transvascular BBB transport.”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [659]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“whereas 8085% is removed by transvascular BBB transport.”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [659]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Panadrenergic inhibition (i.p. administration of the α1-adrenergic receptor antagonist prazosin, the broad β-adrenergic receptor antagonist propranolol, and the α2-adrenergic antagonist atipamezole, PPA13,14) blocked the LC-induced decrease in blood albumin signal (Figure 1H).”
From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [14]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The results presented here provide further support to prior studies that identified sleep as a key driver of glymphatic flow in the rodent and human brain14,16,19,63.”
From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [14]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Such valves will, combined with the oscillatory pressure imposed by the vascular dynamics and the enlarged brain interstitial space, propel CSF influx as a consequence of reduced parenchymal resistance toward fluid flow during sleep14.”
From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [14]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“No statistical methods were used to predetermine sample sizes but our sample sizes are similar to those reported in previous publications3,4,12.”
From Brain clearance is reduced during sleep and anesthesia (2024) · cites this paper as [3]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Natural sleep in animal studies has been shown to associate with increased size of the interstitial space, facilitating increased convective exchange of CSF with interstitial fluid and clearance of macromolecules (23).”
From Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. (2018) · cites this paper as [23]
The cited source says what the claim attributes to it.
In the citing paper
“Sleep is also associated with increased interstitial fluid volume and clearance of metabolic waste products into the CSF (16)”
From Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep (2019) · cites this paper as [16]
The cited source says what the claim attributes to it.
In the citing paper
“Glymphatic fluid transport is enhanced during sleep14–19.”
From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [14]
The cited source says what the claim attributes to it.
In the citing paper
“the reduced resistance towards fluid movement facilitates fluid dispersion within the tissue14.”
From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [14]
The cited source says what the claim attributes to it.
In the citing paper
“The interstitial space expands by as much as 60% during sleep and anesthesia”
From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [14]
The cited source says what the claim attributes to it.
In the citing paper
“confirmed the earlier observation that CSF tracer influx was significantly higher in mice that had been sleeping during the experiment than mice that had been kept awake (Figure S4C–E)14.”
From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [14]
In the citing paper
“Sleep can increase CSF circulation and accelerate transport and clearance of Aβ [419].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [419]
In the citing paper
“The glymphatic system, which clears the brain of protein waste products, is mostly active during sleep.”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [35]
In the citing paper
“Brain fluid transport initiates and proceeds during NREM sleep, and CSF tracer influx correlates with the prevalence of EEG slow wave activity (35, 36).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [35]
In the citing paper
“Fluid flow through the glymphatic system is thus inextricably linked with sleep, to the extent that flow appears to stop with the onset of wakefulness.”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [35]
In the citing paper
“glymphatic clearance is temporally regulated and cyclically so, in that fluid transport is enabled by sleep and suppressed during wakefulness.”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [35]
In the citing paper
“This finding is consistent with several studies suggesting that the function of sleep is restorative and involves metabolite clearance from the brain (9), and that sleep restores antioxidant balance in peripheral tissues (46).”
From Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt (2015) · cites this paper as [9]
In the citing paper
“Neurons, glia cells, and nerve fibers themselves can synthesize cytokines and chemokines, demonstrating a further pathway of brain-to-immune signaling (70, 592).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [592]
In the citing paper
“during sleep, the glymphatic system285 exchanges cerebrospinal fluid with interstitial fluid and clears Aβ286”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [285]
In the citing paper
“A landmark study in mice demonstrating that wakefulness suppresses the outflow of cerebral spinal fluid from the brain, whereas sleep leads to an increase in convective fluxes of fluid, effectively promoting the clearance of neurotoxic metabolics, including Aβ.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [285]
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Cited works that were retracted
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A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
In the paper
“10.1523/JNEUROSCI.0581-12.2012”
Cited work 10.1523/jneurosci.0581-12.2012 · retraction date not known · this paper published 2013-10-18
Citations
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Metadata
- Authors
- Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., O’Donnell, J., Christensen, D. J., Nicholson, C., Iliff, J. J., Takano, T., Deane, R., & Nedergaard, M.
- Affiliations
- University of Rochester Medicine (US)
- NYU Langone Health (US)
- Corresponding author
- Xie, Lulu
- Kang, Hongyi
- Nedergaard, Maiken
- ORCID
- Venue
- Science
- Published
- 2013-10-18
- Volume
- 342
- Issue
- 6156
- Pages
- 373-377
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3880190
- OpenAlex
- W2163225965
- Semantic Scholar
- 014fa65ae6f6f866bc132c1bcccd045b16432f53
- Cited by
- 5,411
- References
- 47
- Citations by year
- 2026: 656 · 2025: 664 · 2024: 528 · 2023: 541 · 2022: 466 · 2021: 462 · 2020: 457 · 2019: 371 · 2018: 310 · 2017: 308 · 2016: 239 · 2015: 243 · 2014: 142 · 2013: 18
- FWCI
- 116.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Israel Science Foundation
- National Institute of Neurological Disorders and Stroke (R01NS078304, NS028642, R01NS078167, R01NS075177, NS078167, R01NS028642, NS078304))
- National Institute of Dental and Craniofacial Research (R01DE022743)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- sleep, cerebrospinal fluid, interstitial fluid, brain waste clearance, amyloid-beta clearance, interstitial space, metabolic homeostasis, anesthesia, two-photon imaging
- MeSH terms
- Quaternary Ammonium Compounds, Animals, Brain, Cerebral Cortex, Cerebrospinal Fluid, Diffusion, Electroencephalography, Extracellular Space, Male, Mice, Inbred C57BL, Receptors, Adrenergic, Sleep, Wakefulness, Amyloid beta-Peptides, Adrenergic Antagonists, Neurodegenerative Diseases, Intracellular Space, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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