Endothelial Transient Receptor Potential Conical Channel (TRPC)-3 Activation Induces Vasogenic Edema Formation in the Rat Piriform Cortex Following Status Epilepticus

Ryu, Hea Jin; Kim, Jieun; Kim, Yeon-Joo; Kim, Ji-Yang; Kim, Won I L; Choi, So-Yeon; Kim, Min-Ju; Kang, Tae‐Cheon

doi:10.1007/s10571-013-9931-x

Cited by 19 publications

(10 citation statements)

References 51 publications

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“…Regarding TRPA1 and TRPC3 not likely described in glioma, some studies highlighted their involvement in other brain vasculature diseases, exerting a protective role against ischemic damage, controlling vasodilation in brain endothelial cells (Sullivan et al, 2016;Pires and Earley, 2018). TRPC3, when overexpressed, would lead to an increase in the BBB permeability, leading to vasogenic edema formation (Ryu et al, 2013).…”

Section: Future Perspectivesmentioning

confidence: 99%

TRP Channels in Brain Tumors

Chinigò

Castel

Chever

et al. 2021

Front. Cell Dev. Biol.

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Malignant glioma including glioblastoma (GBM) is the most common group of primary brain tumors. Despite standard optimized treatment consisting of extensive resection followed by radiotherapy/concomitant and adjuvant therapy, GBM remains one of the most aggressive human cancers. GBM is a typical example of intra-heterogeneity modeled by different micro-environmental situations, one of the main causes of resistance to conventional treatments. The resistance to treatment is associated with angiogenesis, hypoxic and necrotic tumor areas while heterogeneity would accumulate during glioma cell invasion, supporting recurrence. These complex mechanisms require a focus on potential new molecular actors to consider new treatment options for gliomas. Among emerging and underexplored targets, transient receptor potential (TRP) channels belonging to a superfamily of non-selective cation channels which play critical roles in the responses to a number of external stimuli from the external environment were found to be related to cancer development, including glioma. Here, we discuss the potential as biological markers of diagnosis and prognosis of TRPC6, TRPM8, TRPV4, or TRPV1/V2 being associated with glioma patient overall survival. TRPs-inducing common or distinct mechanisms associated with their Ca2+-channel permeability and/or kinase function were detailed as involving miRNA or secondary effector signaling cascades in turn controlling proliferation, cell cycle, apoptotic pathways, DNA repair, resistance to treatment as well as migration/invasion. These recent observations of the key role played by TRPs such as TRPC6 in GBM growth and invasiveness, TRPV2 in proliferation and glioma-stem cell differentiation and TRPM2 as channel carriers of cytotoxic chemotherapy within glioma cells, should offer new directions for innovation in treatment strategies of high-grade glioma as GBM to overcome high resistance and recurrence.

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Section: Future Perspectivesmentioning

confidence: 99%

TRP Channels in Brain Tumors

Chinigò

Castel

Chever

et al. 2021

Front. Cell Dev. Biol.

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“…The canonical transient receptor potential 3 (TRPC3) channel has been increasingly implicated in SE [12][13][14] , and we recently reported that TRPC3 channels enhance seizure intensity 15 . TRPC3 channels are non-selective cation channels known primarily for their importance in regulating intracellular calcium.…”

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confidence: 99%

Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticus

Cozart

Phelan

et al. 2020

Sci Rep

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Human status epilepticus (SE) is associated with a pathological reduction in cerebral blood flow termed the inverse hemodynamic response (IHR). Canonical transient receptor potential 3 (TRPC3) channels are integral to the propagation of seizures in SE, and vascular smooth muscle cell (VSMC) TRPC3 channels participate in vasoconstriction. Therefore, we hypothesize that cerebrovascular TRPC3 channels may contribute to seizure-induced IHR. To examine this possibility, we developed a smooth muscle-specific TRPC3 knockout (TRPC3smcKO) mouse. To quantify changes in neurovascular coupling, we combined laser speckle contrast imaging with simultaneous electroencephalogram recordings. Control mice exhibited multiple IHRs, and a limited increase in cerebral blood flow during SE with a high degree of moment-to-moment variability in which blood flow was not correlated with neuronal activity. In contrast, TRPC3smcKO mice showed a greater increase in blood flow that was less variable and was positively correlated with neuronal activity. Genetic ablation of smooth muscle TRPC3 channels shortened the duration of Se by eliminating a secondary phase of intense seizures, which was evident in littermate controls. Our results are consistent with the idea that TRPC3 channels expressed by cerebral VSMcs contribute to the iHR during Se, which is a critical factor in the progression of Se. Status epilepticus (SE) is a life-threatening condition characterized by continuous or rapidly repeating seizures 1. Attempts to understand the pathogenesis and progression of SE have historically focused on neuronal dysfunction, particularly hyperexcitation, rather than on a broader perspective that allows for the culpability of both neuronal and vascular abnormalities as contributors to SE. Blood flow is tightly coupled to the metabolic demands of local neuronal activity in a process termed neurovascular coupling, which is facilitated by highly complex interactions between neurons, glia, and vascular cells 2-5. Brain homeostasis and proper neuronal function fully rely on intact neurovascular coupling. Accepting this tenet, it is not surprising that disruption of neurovascular coupling is increasingly recognized as a shared feature of many neurological disorders, including epileptic seizures 2,3,6,7 , and cerebrovascular dysfunction may be a key feature of SE. Acute insults to the brain are widely reported to result in spreading depolarization 6,8-10 , or waves of neuronal depolarization emanating from the locus of the trauma and proceeding outwardly through healthy tissue. Such spreading depolarizations are observed clinically in traumatic brain injury 8,9 , stroke 9 , brain hemorrhage 6,9,10 , and epileptic seizure 6,9,10. Spreading depolarizations have been shown to induce a transient hyperperfusion of blood flow, which is often followed by one or more periods of hypoperfusion 6,8-10. This hypoperfusion, known as the inverse hemodynamic response (IHR), is thought to be mediated by vasoconstriction of small intracerebral arteries and arterioles 9,10....

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“…For instance, TRPC1 and TRPC4 mediate thrombin-induced permeability increase in HUVEC monolayers (Paria et al, 2006) and mouse lung vasculature (Tiruppathi et al, 2002), respectively. Likewise, TRPC3 overexpression/hyperactivation has been associated to the exaggerated increase in blood-brain barrier (BBB) permeability observed in response to status epilepticus (Ryu et al, 2013). Furthermore, TRPM2 mediates H 2 O 2 -induced endothelial hyperpermeability in human pulmonary artery endothelial cells (Hecquet et al, 2008), whereas TRPC6 sustains endotoxin-induced disruption of pulmonary vascular barrier (Tauseef et al, 2012) and pulmonary ischemia-reperfusion evoked edema (Weissmann et al, 2012) in mice.…”

Section: Trp Channels Regulate Multiple Endothelial Cell Functionsmentioning

confidence: 99%

Endothelial Transient Receptor Potential Channels and Vascular Remodeling: Extracellular Ca2 + Entry for Angiogenesis, Arteriogenesis and Vasculogenesis

et al. 2020

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Vasculogenesis, angiogenesis and arteriogenesis represent three crucial mechanisms involved in the formation and maintenance of the vascular network in embryonal and post-natal life. It has long been known that endothelial Ca 2+ signals are key players in vascular remodeling; indeed, multiple pro-angiogenic factors, including vascular endothelial growth factor, regulate endothelial cell fate through an increase in intracellular Ca 2+ concentration. Transient Receptor Potential (TRP) channel consist in a superfamily of non-selective cation channels that are widely expressed within vascular endothelial cells. In addition, TRP channels are present in the two main endothelial progenitor cell (EPC) populations, i.e., myeloid angiogenic cells (MACs) and endothelial colony forming cells (ECFCs). TRP channels are polymodal channels that can assemble in homo-and heteromeric complexes and may be sensitive to both pro-angiogenic cues and subtle changes in local microenvironment. These features render TRP channels the most versatile Ca 2+ entry pathway in vascular endothelial cells and in EPCs. Herein, we describe how endothelial TRP channels stimulate vascular remodeling by promoting angiogenesis, arteriogenesis and vasculogenesis through the integration of multiple environmental, e.g., extracellular growth factors and chemokines, and intracellular, e.g., reactive oxygen species, a decrease in Mg 2+ levels, or hypercholesterolemia, stimuli. In addition, we illustrate how endothelial TRP channels induce neovascularization in response to synthetic agonists and small molecule drugs. We focus the attention on TRPC1, TRPC3, TRPC4, TRPC5, TRPC6, TRPV1, TRPV4, TRPM2, TRPM4, TRPM7, TRPA1, that were shown to be involved in angiogenesis, arteriogenesis and vasculogenesis. Finally, we discuss the role of endothelial TRP channels in aberrant tumor vascularization by focusing on TRPC1, TRPC3, TRPV2, TRPV4, TRPM8, and TRPA1. These observations suggest that endothelial TRP channels represent potential therapeutic targets in multiple disorders featured by abnormal vascularization, including cancer, ischemic disorders, retinal degeneration and neurodegeneration.

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Endothelial Transient Receptor Potential Conical Channel (TRPC)-3 Activation Induces Vasogenic Edema Formation in the Rat Piriform Cortex Following Status Epilepticus

Cited by 19 publications

References 51 publications

TRP Channels in Brain Tumors

TRP Channels in Brain Tumors

Vascular smooth muscle TRPC3 channels facilitate the inverse hemodynamic response during status epilepticus

Endothelial Transient Receptor Potential Channels and Vascular Remodeling: Extracellular Ca2 + Entry for Angiogenesis, Arteriogenesis and Vasculogenesis

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