Role of TRP ion channels in cerebral circulation and neurovascular communication

Kuppusamy, Maniselvan; Ottolini, Matteo; Sonkusare, Swapnil K.

doi:10.1016/j.neulet.2021.136258

Cited by 8 publications

(13 citation statements)

References 132 publications

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“…Mechanically gated ion channels have recently been implicated as playing key roles in the homeostasis of the CNS and in mediating mechanotransduction in neural populations [49,50,52,60,61]. Indeed several ion channels have been shown to play a role in the reception of mechanical cues and have been shown to become perturbed in the progression of multiple disease states [25,48,68].…”

Section: Discussionmentioning

confidence: 99%

“…Despite insightful advances in mechanobiology, the mechanism by which cells of the CNS can sense mechanical variations and the molecular pathways which initiate gliosis are not fully understood. Recently, mechanosensitive (MS) ion channels have come to the forefront of neuromechanobiology and have been shown to undergo activation or differential expression in response to mechanical stimuli within the central nervous system (CNS) [49], with important functions in blood-brain barrier maintenance [50], neural differentiation [51][52][53][54][55], nociception [56][57][58][59], neural-glia communication [60][61][62] and glia activation [63][64][65][66][67]. Critically, MS channels have been observed as perturbed in neurodegenerative disorders [68] including Alzheimer's disease [69][70][71], myelination disorders [72][73][74][75], migraine [76][77][78][79] and glioma [80][81][82].…”

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confidence: 99%

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Micromotion derived fluid shear stress mediates peri-electrode gliosis through mechanosensitive ion channels

Trotier

Bagnoli

Walski

et al. 2023

Preprint

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Clinical applications for neural implant technologies are steadily advancing. Yet, despite clinical successes, neuroelectrode-based therapies require invasive neurosurgery and can subject local soft-tissues to micro-motion induced mechanical shear, leading to the development of peri-implant scaring. This reactive glial tissue creates a physical barrier to electrical signal propagation, leading to loss of device function. Although peri-electrode gliosis is a well described contributor to neuroelectrode failure, the mechanistic basis behind the initiation and progression of glial scarring remains poorly understood. Here, we develop an in silico model of electrode-induced shear stress to evaluate the evolution of the peri-electrode fluid-filled void, encompassing a solid and viscoelastic liquid/solid interface. This model was subsequently used to inform an in vitro parallel-plate flow model of micromotion mediated peri-electrode fluid shear stress. Ventral mesencephalic E14 rat embryonic in vitro cultures exposed to physiologically relevant fluid shear exhibited upregulation of gliosis-associated proteins and the overexpression of two mechanosensitive ion channel receptors, PIEZO1 and TRPA1, confirmed in vivo in a neural probe induced rat glial scar model. Finally, it was shown in vitro that chemical inhibition/activation of PIEZO1 could exacerbate or attenuate astrocyte reactivity as induced by fluid shear stress and that this was mitochondrial dependant. Together, our results suggests that mechanosensitive ion channels play a major role in the development of the neuroelectrode micromotion induced glial scar and that the modulation of PIEZO1 and TRPA1 through chemical agonist/antagonist may promote chronic electrode stability in vivo.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Micromotion derived fluid shear stress mediates peri-electrode gliosis through mechanosensitive ion channels

Trotier

Bagnoli

Walski

et al. 2023

Preprint

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“…For all these reasons, TRP channels are important mediators of several microvascular functions and may be important tools in the prevention of aging-related cognitive deficits ( Kuppusamy et al, 2021 ). Herein, we provide an overview of the TRP channels-dependent molecular mechanisms involved in aging and specifically in the modification of endothelial cells’ activity, highlighting their possible therapeutic role.…”

Section: Age-related Cerebrovascular Changesmentioning

confidence: 99%

“…The production of poly-ADPR activates TRPM2 channel, thereby inducing an endothelial Ca 2+ overload, endothelial dysfunction, and neurovascular impairment ( Park et al, 2014 ). Furthermore, endothelial TRPA1 channels play a crucial role in CBF regulation at the artery, arteriole, and capillary level ( Kuppusamy et al, 2021 ). For instance, TRPA1 is activated by superoxide anions generated by the NADPH oxidase isoform 2 (NOX2) enzyme.…”

Section: Trp Channels In Cerebrovascular Diseasesmentioning

confidence: 99%

“…Nowadays, 28 members have been discovered, and are continuously studied in physiological and pathophysiological conditions as a promising therapeutic target for several neurological and cardiovascular disorders. TRP channels have emerged as important regulators of neurovascular functions, and their proper function is fundamental to maintain normal brain activity ( Kuppusamy et al, 2021 ). In the last few decades, growing evidence highlights the importance of healthy lifestyle habits to prevent cardiovascular and neurovascular disorders typical of aging ( Csipo et al, 2019 ; Balasubramanian et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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The role of endothelial TRP channels in age-related vascular cognitive impairment and dementia

Negri

Sanford

Shi

et al. 2023

Front. Aging Neurosci.

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Transient receptor potential (TRP) proteins are part of a superfamily of polymodal cation channels that can be activated by mechanical, physical, and chemical stimuli. In the vascular endothelium, TRP channels regulate two fundamental parameters: the membrane potential and the intracellular Ca2+ concentration [(Ca2+)i]. TRP channels are widely expressed in the cerebrovascular endothelium, and are emerging as important mediators of several brain microvascular functions (e.g., neurovascular coupling, endothelial function, and blood–brain barrier permeability), which become impaired with aging. Aging is the most significant risk factor for vascular cognitive impairment (VCI), and the number of individuals affected by VCI is expected to exponentially increase in the coming decades. Yet, there are currently no preventative or therapeutic treatments available against the development and progression of VCI. In this review, we discuss the involvement of endothelial TRP channels in diverse physiological processes in the brain as well as in the pathogenesis of age-related VCI to explore future potential neuroprotective strategies.

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Micromotion Derived Fluid Shear Stress Mediates Peri‐Electrode Gliosis through Mechanosensitive Ion Channels

et al. 2023

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The development of bioelectronic neural implant technologies has advanced significantly over the past 5 years, particularly in brain–machine interfaces and electronic medicine. However, neuroelectrode‐based therapies require invasive neurosurgery and can subject neural tissues to micromotion‐induced mechanical shear, leading to chronic inflammation, the formation of a peri‐electrode void and the deposition of reactive glial scar tissue. These structures act as physical barriers, hindering electrical signal propagation and reducing neural implant functionality. Although well documented, the mechanisms behind the initiation and progression of these processes are poorly understood. Herein, in silico analysis of micromotion‐induced peri‐electrode void progression and gliosis is described. Subsequently, ventral mesencephalic cells exposed to milliscale fluid shear stress in vitro exhibited increased expression of gliosis‐associated proteins and overexpression of mechanosensitive ion channels PIEZO1 (piezo‐type mechanosensitive ion channel component 1) and TRPA1 (transient receptor potential ankyrin 1), effects further confirmed in vivo in a rat model of peri‐electrode gliosis. Furthermore, in vitro analysis indicates that chemical inhibition/activation of PIEZO1 affects fluid shear stress mediated astrocyte reactivity in a mitochondrial‐dependent manner. Together, the results suggest that mechanosensitive ion channels play a major role in the development of a peri‐electrode void and micromotion‐induced glial scarring at the peri‐electrode region.

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Role of TRP ion channels in cerebral circulation and neurovascular communication

Cited by 8 publications

References 132 publications

Micromotion derived fluid shear stress mediates peri-electrode gliosis through mechanosensitive ion channels

Micromotion derived fluid shear stress mediates peri-electrode gliosis through mechanosensitive ion channels

The role of endothelial TRP channels in age-related vascular cognitive impairment and dementia

Micromotion Derived Fluid Shear Stress Mediates Peri‐Electrode Gliosis through Mechanosensitive Ion Channels

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