Direct Measurement of Cerebrospinal Fluid Production in Mice

Liu, Guojun; Mestre, Humberto; Sweeney, Amanda M.; Sun, Qian; Weikop, Pia; Du, Ting

doi:10.1016/j.celrep.2020.108524

Cited by 75 publications

(82 citation statements)

References 65 publications

(89 reference statements)

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“…Glymphatic function drops dramatically during aging due to various factors. Reduced polarized aquaporin-4 channels on the endfeet of astrocyte cells ( Valenza et al, 2019 ), decreased CSF production ( Liu et al, 2020 ) and CSF pressure, diminished arterial pulsatility ( Mestre et al, 2018b ) could all lead to compromised glymphatic function in aged animals ( Jessen et al, 2015 ). In a recent study, Zhou Y. et al (2020) .…”

Section: Discussionmentioning

confidence: 99%

The Influence of Demographics and Vascular Risk Factors on Glymphatic Function Measured by Diffusion Along Perivascular Space

Zhang

et al. 2021

Front. Aging Neurosci.

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Assessing glymphatic function using in-vivo imaging method is of great value for understanding its contribution to major brain diseases. In the present study, we aim to validate the association between a variety of risk factors and a potential index of glymphatic function—Diffusion Tensor Image Analysis Along the Perivascular Space (ALPS index). We enrolled 142 subjects from communities and performed multi-modality magnetic resonance imaging scans. The ALPS index was calculated from diffusion tensor imaging data, and its associations with demographic factors, vascular factors were investigated using regression analyses. We found that the ALPS index was negatively associated with age (β = −0.284, p < 0.001). Compared to males, females had significantly higher ALPS index (β = −0.243, p = 0.001). Hypertensive subjects had significantly lower ALPS index compared to non-hypertensive subjects (β = −0.189, p = 0.013). Furthermore, venous disruption could decrease ALPS index (β = −0.215, p = 0.003). In general, our results are in consistent with previous conceptions and results from animal studies about the pathophysiology of glymphatic dysfunction. Future studies utilizing this method should consider introducing the above-mentioned factors as important covariates.

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Section: Discussionmentioning

confidence: 99%

The Influence of Demographics and Vascular Risk Factors on Glymphatic Function Measured by Diffusion Along Perivascular Space

Zhang

et al. 2021

Front. Aging Neurosci.

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“…Current study quantified the flow rate of ICF, i.e., 891-1153 ml/100ml/min in LV and 3V. A recent invasive study on mouse brain states the CSF outflow from both LV and 3V is in the order of magnitude of 0.1 µL/min (48), which is minute compare to the ICF flow obtained by our current study (32-44 µL/min in 4 µL LV). Our result indicated that the CSF secreted from parenchyma is reabsorbed by the periventricular ependymal layers as indicated in Fig.…”

Section: Discussionmentioning

confidence: 46%

“…Water continuously moves in and out of the ependymal layer, a process resembles the intracellular and extracellular water movement, is one possible reason for the rapid turnover number. The difference between CSF secreted from CP (0.52-0.8 µL/min) (47) and the total outflow (0.1 µL/min) (48) suggests that a large portion of the CSF in ventricles is absorbed by the surrounding parenchyma. But due to the large mass of the parenchyma, kinetically speaking, the absorption is a prolonged process (less than 15 ml/100mg/min) as confirmed by the T2-PALAN measurement.…”

Section: Discussionmentioning

confidence: 99%

Interstitial and cerebrospinal fluid exchanging process revealed by phase alternate labeling with null recovery MRI

2021

Preprint

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Purpose: To develop Phase Alternate LAbeling with Null recovery (PALAN) MRI methods for the quantification of interstitial to cerebrospinal fluid flow (ICF) and cerebrospinal to interstitial fluid flow (CIF) in the brain. Method: In both T1-PALAN and apparent diffusion coefficient (ADC)-PALAN MRI methods, the cerebrospinal fluid (CSF) signal was nulled, while the residual interstitial fluid (ISF) was labeled by alternating the phase of pulses. ICF was extracted from the difference between the recovery curves of CSF with and without labeling. Similarly, CIF was measured by the T2-PALAN MRI method by labeling CSF, which took advance of the significant T2 difference between CSF and parenchyma. Results: Both T1-PALAN and ADC-PALAN observed a rapid occurrence of ICF at 67±56 ms and 13±2 ms interstitial fluid transit times, respectively. ICF signal peaked at 1.5 s for both methods. ICF was 1153±270 ml/100ml/min with T1-PALAN in the third and lateral ventricles, which was higher than 891±60 ml/100ml/min obtained by ADC-PALAN. The results of the T2-PALAN suggested the ISF exchanging from ependymal layer to the parenchyma was extremely slow. Conclusion: The PALAN methods are suitable tools to study ISF and CSF flow kinetics in the brain.

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“…Increased sympathetic tone inhibits carbonic anhydrase associated with the choroidal epithelium and likely reduces CSF production and glymphatic circulation (Damkier et al, 2013 ; Benveniste et al, 2017 ). Recently, Liu et al also reported that CSF production was increased by a combination of α 1 -, α 2 -, and non-selective β-adrenergic receptor antagonists, as well as some anesthetics, including isoflurane, ketamine, and xylazine (Liu G. et al, 2020 ).…”

Section: The Underlying Mechanism Of Altered Glymphatic Function During Intraoperative Anesthesia Managementmentioning

confidence: 99%

Dysfunction of the Glymphatic System as a Potential Mechanism of Perioperative Neurocognitive Disorders

Ren

Liu

Lian

et al. 2021

Front. Aging Neurosci.

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Perioperative neurocognitive disorder (PND) frequently occurs in the elderly as a severe postoperative complication and is characterized by a decline in cognitive function that impairs memory, attention, and other cognitive domains. Currently, the exact pathogenic mechanism of PND is multifaceted and remains unclear. The glymphatic system is a newly discovered glial-dependent perivascular network that subserves a pseudo-lymphatic function in the brain. Recent studies have highlighted the significant role of the glymphatic system in the removal of harmful metabolites in the brain. Dysfunction of the glymphatic system can reduce metabolic waste removal, leading to neuroinflammation and neurological disorders. We speculate that there is a causal relationship between the glymphatic system and symptomatic progression in PND. This paper reviews the current literature on the glymphatic system and some perioperative factors to discuss the role of the glymphatic system in PND.

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Direct Measurement of Cerebrospinal Fluid Production in Mice

Cited by 75 publications

References 65 publications

The Influence of Demographics and Vascular Risk Factors on Glymphatic Function Measured by Diffusion Along Perivascular Space

The Influence of Demographics and Vascular Risk Factors on Glymphatic Function Measured by Diffusion Along Perivascular Space

Interstitial and cerebrospinal fluid exchanging process revealed by phase alternate labeling with null recovery MRI

Dysfunction of the Glymphatic System as a Potential Mechanism of Perioperative Neurocognitive Disorders

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