Diffusion MRI reveals in vivo and non-invasively changes in astrocyte function induced by an aquaporin-4 inhibitor

Debacker, Clément; Djemaï, Boucif; Tsurugizawa, Tomokazu; Ciobanu, Luisa; Bihan, Denis Le

doi:10.1101/2020.02.13.947291

Cited by 5 publications

(4 citation statements)

References 52 publications

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“…The results of this study showed that a marker of diffusion called the S-index was significantly reduced by the suppression of AQP4 function. 52 Fundamentally, to evaluate the permeability of cell membrane with and without AQP4, diffusion time is important. An in vitro study showed that multi-b and multi-diffusion-time diffusion-weighted MR imaging on AQP4-expressing and -non-expressing cells demonstrated a clear difference between the signals from the two cell types.…”

Section: Challenges To Visualizing Glymphatic System Function By Mr I...mentioning

confidence: 99%

The Glymphatic System: A Review of the Challenges in Visualizing its Structure and Function with MR Imaging

Naganawa

Taoka

2022

magn reson med sci

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The central nervous system (CNS) was previously thought to be the only organ system lacking lymphatic vessels to remove waste products from the interstitial space. Recently, based on the results from animal experiments, the glymphatic system was hypothesized. In this hypothesis, cerebrospinal fluid (CSF) enters the periarterial spaces, enters the interstitial space of the brain parenchyma via aquaporin-4 (AQP4) channels in the astrocyte end feet, and then exits through the perivenous space, thereby clearing waste products. From the perivenous space, the interstitial fluid drains into the subarachnoid space and meningeal lymphatics of the parasagittal dura. It has been reported that the glymphatic system is particularly active during sleep. Impairment of glymphatic system function might be a cause of various neurodegenerative diseases such as Alzheimer's disease, normal pressure hydrocephalus, glaucoma, and others. Meningeal lymphatics regulate immunity in the CNS. Many researchers have attempted to visualize the function and structure of the glymphatic system and meningeal lymphatics in vivo using MR imaging. In this review, we aim to summarize these in vivo MR imaging studies and discuss the significance, current limitations, and future directions. We also discuss the significance of the perivenous cyst formation along the superior sagittal sinus, which is recently discovered in the downstream of the glymphatic system.

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Section: Challenges To Visualizing Glymphatic System Function By Mr I...mentioning

confidence: 99%

The Glymphatic System: A Review of the Challenges in Visualizing its Structure and Function with MR Imaging

Naganawa

Taoka

2022

magn reson med sci

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“…Such prediction suits both FEXI and DKI(t) as DKI(t) prefers long diffusion time to reduce the influence of microstructure whereas the effects of background gradient or other factors make short mixing time FEXI measurements more reliable. Further studies using animal models with altered membrane permeability via aquaporin channels [61][62][63] will allow us to evaluate these diffusion MRI based techniques to map tissue exchange.…”

Section: Comparing Fexi and Dki(t)mentioning

confidence: 99%

Measuring water exchange on a preclinical MRI system using filter exchange and diffusion time dependent kurtosis imaging

Li¹,

Fieremans²,

Novikov³

et al. 2022

Magnetic Resonance in Med

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Purpose Filter exchange imaging (FEXI) and diffusion time (t)‐dependent diffusion kurtosis imaging (DKI(t)) are both sensitive to water exchange between tissue compartments. The restrictive effects of tissue microstructure, however, introduce bias to the exchange rate obtained by these two methods, as their interpretation conventionally rely on the Kärger model of barrier limited exchange between Gaussian compartments. Here, we investigated whether FEXI and DKI(t) can provide comparable exchange rates in ex vivo mouse brains. Theory and Methods FEXI and DKI(t) data were acquired from ex vivo mouse brains on a preclinical MRI system. Phase cycling and negative slice prewinder gradients were used to minimize the interferences from imaging gradients. Results In the corpus callosum, apparent exchange rate (AXR) from FEXI correlated with the exchange rate (the inverse of exchange time, 1/τex) from DKI(t) along the radial direction. In comparison, discrepancies between FEXI and DKI(t) were found in the cortex due to low filter efficiency and confounding effects from tissue microstructure. Conclusion The results suggest that FEXI and DKI(t) are sensitive to the same exchange processes in white matter when separated from restrictive effects of microstructure. The complex microstructure in gray matter, with potential exchange among multiple compartments and confounding effects of microstructure, still pose a challenge for FEXI and DKI(t).

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“…First, we did not assess glymphatic function using in vivo imaging. Several MRI methods have been developed for glymphatic CSF and solute transport analysis [52,[127][128][129]. Second, we did not include the quantification of AQP4 mRNA expression in mouse brain tissues.…”

Section: Discussionmentioning

confidence: 99%

Aquaporin 4 is differentially increased and depolarized in association with tau and amyloid-beta

Kecheliev

Boss

Maheshwari

et al. 2022

Preprint

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Neurovascular-glymphatic dysfunction plays an important role in Alzheimer’s disease and has been analyzed mainly in association with amyloid-beta (Aβ) pathology. The neurovascular-glymphatic link with tauopathies has not been well elucidated. Here, we aimed to investigate the alterations in the neurovasculature and map the aquaporin 4 (AQP4) distribution and depolarization associated with tau and Aβ. Perfusion, susceptibility weighted imaging and structural magnetic resonance imaging (MRI) were performed in the pR5 P301L mouse model of 4-repeat tau and the arcAβ mouse model of amyloidosis. Immunofluorescence staining was performed using antibodies against AQP4, CD31, astroglia (GFAP, s100β), phospho-tau (AT-8) and Aβ (6E10) in brain tissue slices from P301L, arcAβ and nontransgenic mice. P301L mice showed regional atrophy, preserved cerebral blood flow and reduced cerebral vessel density compared to nontransgenic mice, while arcAβ mice showed cerebral microbleeds and reduced cerebral vessel density. AQP4 depolarization and peri-tau enrichment in the hippocampus and increased AQP4 levels in the forebrain and hippocampus were detected in P301L mice compared to nontransgenic mice. In comparison, cortical AQP4 depolarization and cortical/hippocampal peri-plaque increases were observed in arcAβ mice. Increased s100β-GFAP fluorescence intensities indicative of reactive astrocytes were detected surrounding tau inclusions in P301L mice and Aβ plaques in arcAβ mice. In conclusion, we observed a divergent region-specific AQP4 increase and association with phospho-tau and Aβ pathologies.

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Diffusion MRI reveals in vivo and non-invasively changes in astrocyte function induced by an aquaporin-4 inhibitor

Cited by 5 publications

References 52 publications

The Glymphatic System: A Review of the Challenges in Visualizing its Structure and Function with MR Imaging

The Glymphatic System: A Review of the Challenges in Visualizing its Structure and Function with MR Imaging

Measuring water exchange on a preclinical MRI system using filter exchange and diffusion time dependent kurtosis imaging

Aquaporin 4 is differentially increased and depolarized in association with tau and amyloid-beta

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