Evaluation of AQP4/TRPV4 Channel Co-expression, Microvessel Density, and its Association with Peritumoral Brain Edema in Intracranial Meningiomas

Faropoulos, Konstantinos; Polia, Afroditi; Tsakona, Chrisi; Pitaraki, Eleanna; Moutafidi, Athanasia; Gatzounis, George; Assimakopoulou, Martha

doi:10.1007/s12031-021-01801-1

Cited by 11 publications

(7 citation statements)

References 50 publications

(69 reference statements)

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“…This response of the AQP4 −/− /TRPV4 −/− mice to pMCAO indicates an interplay between these two channels, which was previously suggested in the experiments using cultured glia (Benfenati et al, 2011;Jo et al, 2015;Redmon et al, 2021) or in meningiomas (Faropoulos et al, 2021), where AQP4-mediated water fluxes promote the activation of TRPV4, whereas Ca 2+ entry through TRPV4 channels reciprocally modulates volume regulation, swelling, and Aqp4 gene expression (Jo et al, 2015). This interplay is especially prominent during the acute phase of ischemia, because after 7 days the damage detected in the AQP4 −/− /TRPV4 −/− mice was comparable to that observed in the Ctrl.…”

Section: The Deteriorating Effect Of Aqp4 or Trpv4 Deletion On The Si...supporting

confidence: 69%

“…The activation of TRPV4 channels increases intracellular Ca 2+ concentration, which triggers RVD and leads to water efflux via the AQP4 channels and, therefore, strongly affects the cellular response to the development of cytotoxic brain edema (Benfenati et al, 2011;Jo et al, 2015). In addition, recent study showed correlation between the increased expression of AQP4/TRPV4 complex and larger peri-tumor edema in patients (Faropoulos et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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The absence of AQP4/TRPV4 complex substantially reduces acute cytotoxic edema following ischemic injury

Suchá

Heřmanová

Chmelova

et al. 2022

Front. Cell. Neurosci.

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IntroductionAstrocytic Aquaporin 4 (AQP4) and Transient receptor potential vanilloid 4 (TRPV4) channels form a functional complex that likely influences cell volume regulation, the development of brain edema, and the severity of the ischemic injury. However, it remains to be fully elucidated whether blocking these channels can serve as a therapeutic approach to alleviate the consequences of having a stroke.Methods and resultsIn this study, we used in vivo magnetic resonance imaging (MRI) to quantify the extent of brain lesions one day (D1) and seven days (D7) after permanent middle cerebral artery occlusion (pMCAO) in AQP4 or TRPV4 knockouts and mice with simultaneous deletion of both channels. Our results showed that deletion of AQP4 or TRPV4 channels alone leads to a significant worsening of ischemic brain injury at both time points, whereas their simultaneous deletion results in a smaller brain lesion at D1 but equal tissue damage at D7 when compared with controls. Immunohistochemical analysis 7 days after pMCAO confirmed the MRI data, as the brain lesion was significantly greater in AQP4 or TRPV4 knockouts than in controls and double knockouts. For a closer inspection of the TRPV4 and AQP4 channel complex in the development of brain edema, we applied a real-time iontophoretic method in situ to determine ECS diffusion parameters, namely volume fraction (α) and tortuosity (λ). Changes in these parameters reflect alterations in cell volume, and tissue structure during exposure of acute brain slices to models of ischemic conditions in situ, such as oxygen-glucose deprivation (OGD), hypoosmotic stress, or hyperkalemia. The decrease in α was comparable in double knockouts and controls when exposed to hypoosmotic stress or hyperkalemia. However, during OGD, there was no decrease in α in the double knockouts as observed in the controls, which suggests less swelling of the cellular components of the brain.ConclusionAlthough simultaneous deletion of AQP4 and TRPV4 did not improve the overall outcome of ischemic brain injury, our data indicate that the interplay between AQP4 and TRPV4 channels plays a critical role during neuronal and non-neuronal swelling in the acute phase of ischemic injury.

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Section: The Deteriorating Effect Of Aqp4 or Trpv4 Deletion On The Si...supporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

The absence of AQP4/TRPV4 complex substantially reduces acute cytotoxic edema following ischemic injury

Suchá

Heřmanová

Chmelova

et al. 2022

Front. Cell. Neurosci.

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“…Piezo1 have been suggested as potential prognostic biomarkers for the early diagnosis of glioma, 140 , 141 given the level of Piezo1 is positively correlated with the severity of edema and the degree of compression forces. 142 , 143 , 144 …”

Section: The Mscs Respond To Forces From Place‐occupying Damagementioning

confidence: 99%

Mechanobiological insight into brain diseases based on mechanosensitive channels: Common mechanisms and clinical potential

Li,

Zhao,

Tian

et al. 2024

CNS Neurosci Ther

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BackgroundAs physical signals, mechanical cues regulate the neural cells in the brain. The mechanosensitive channels (MSCs) perceive the mechanical cues and transduce them by permeating specific ions or molecules across the plasma membrane, and finally trigger a series of intracellular bioelectrical and biochemical signals. Emerging evidence supports that wide‐distributed, high‐expressed MSCs like Piezo1 play important roles in several neurophysiological processes and neurological disorders.AimsTo systematically conclude the functions of MSCs in the brain and provide a novel mechanobiological perspective for brain diseases.MethodWe summarized the mechanical cues and MSCs detected in the brain and the research progress on the functional roles of MSCs in physiological conditions. We then concluded the pathological activation and downstream pathways triggered by MSCs in two categories of brain diseases, neurodegenerative diseases and place‐occupying damages. Finally, we outlined the methods for manipulating MSCs and discussed their medical potential with some crucial outstanding issues.ResultsThe MSCs present underlying common mechanisms in different brain diseases by acting as the “transportation hubs” to transduce the distinct signal patterns: the upstream mechanical cues and the downstream intracellular pathways. Manipulating the MSCs is feasible to alter the complicated downstream processes, providing them promising targets for clinical treatment.ConclusionsRecent research on MSCs provides a novel insight into brain diseases. The common mechanisms mediated by MSCs inspire a wide range of therapeutic potentials targeted on MSCs in different brain diseases.

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“…TRPV4 has, in addition, been implicated in pulmonary edema formation, partly via the observed down regulation of the co-localized AQP5 in the pulmonary epithelium obtained from TRPV4 - / - mice ( 27 ). Tissue obtained from meningioma patients demonstrated AQP4/TRPV4 co-expression in both edematous and non-edematous meningiomas, although in the surrounding peri-meningioma tissue, only AQP4 was upregulated ( 28 ). TRPV4 thus appears to be involved in physiological and pathophysiological processes involving fluid dynamics, in addition to its roles in skeletal dysplasias [for review of TRPV4 in pathology, see ( 29 )].…”

Section: Cellular Detection Of Volume Changesmentioning

confidence: 99%

TRPing on Cell Swelling - TRPV4 Senses It

Toft-Bertelsen

MacAulay

2021

Front. Immunol.

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The transient receptor potential vanilloid 4 channel (TRPV4) is a non-selective cation channel that is widely expressed and activated by a range of stimuli. Amongst these stimuli, changes in cell volume feature as a prominent regulator of TRPV4 activity with cell swelling leading to channel activation. In experimental settings based on abrupt introduction of large osmotic gradients, TRPV4 activation requires co-expression of an aquaporin (AQP) to facilitate such cell swelling. However, TRPV4 readily responds to cell volume increase irrespectively of the molecular mechanism underlying the cell swelling and can, as such, be considered a sensor of increased cell volume. In this review, we will discuss the proposed events underlying the molecular coupling from cell swelling to channel activation and present the evidence of direct versus indirect swelling-activation of TRPV4. With this summary of the current knowledge of TRPV4 and its ability to sense cell volume changes, we hope to stimulate further experimental efforts in this area of research to clarify TRPV4’s role in physiology and pathophysiology.

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Evaluation of AQP4/TRPV4 Channel Co-expression, Microvessel Density, and its Association with Peritumoral Brain Edema in Intracranial Meningiomas

Cited by 11 publications

References 50 publications

The absence of AQP4/TRPV4 complex substantially reduces acute cytotoxic edema following ischemic injury

The absence of AQP4/TRPV4 complex substantially reduces acute cytotoxic edema following ischemic injury

Mechanobiological insight into brain diseases based on mechanosensitive channels: Common mechanisms and clinical potential

TRPing on Cell Swelling - TRPV4 Senses It

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