Transient receptor potential vanilloid 4 agonist GSK1016790A improves neurological outcomes after intracerebral hemorrhage in mice

Asao, Yasunori; Tobori, Shota; Kakae, Masashi; Nagayasu, Kazuki; Shibasaki, Kazuo; Shirakawa, Hisashi; Kaneko, Shuji

doi:10.1016/j.bbrc.2020.06.103

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…A specific TRPV4 agonist improved selected neurological and motor outcomes in cerebral hemorrhage. Interestingly these effects occurred in the absence of other beneficial changes such as injury-induced increases in brain volume, edema or GFAP- positive astrocytes [95]. Likewise, TRPV4 activation with 4α-phorbol 12,13-didecanoate reduced infarct volume and improved functional outcomes in a (MCAO) model of stroke.…”

Section: Trpv4mentioning

confidence: 96%

“…This may be due to the experimental parameters monitored in each study. For example, activation of TRPV4 may be beneficial in neuronal and endothelial cells [95,96], while TRPV4 antagonism may be beneficial in other cell types [9,93,94,97,98]. The role that TRPV4 plays in each cell type may also differ, for example proliferation in neurons and endothelial cells and inflammation in microglia and astrocytes.…”

Section: Trpv4mentioning

confidence: 99%

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Channels and Transporters in Astrocyte Volume Regulation in Health and Disease

2022

Cell Physiol Biochem

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Astrocytes are the second most abundant cell type in the central nervous system and serve various functions, many of which maintain homeostasis of the intracellular milieu in the face of constant change. In order to accomplish these important functions, astrocytes must regulate their cell volume. In astrocytes, cell volume regulation involves multiple channels and transporters, including AQP4, TRPV4, TRPM4, VRAC, Na+/K+ ATPase, NKCC1 and Kir4.1. AQP4 is a bidirectional water channel directly involved in astrocyte cell volume regulation. AQP4 also forms heteromultimeric complexes with other channels and transporters involved in cell volume regulation. TRPV4, a mechanosensitive channel in involved in osmotic regulation in various cell types, forms a complex with AQP4 to decrease cell volume in response to cell swelling. TRPM4 also forms a complex with AQP4 and SUR1 in response to injury resulting in cell swelling. Another complex forms between Na+/K+ ATPase, AQP4, and mGluR5 to regulate the perisynaptic space. NKCC1 is a co-transporter involved in cell volume increases either independently through cotransport of water or a functional interaction with AQPs. VRAC is implicated in regulatory volume decreases and may also functionally interact with AQP4. Although Kir4.1 colocalizes with AQP4, its role in cell volume regulation is debated. In diseases where fluid/electrolyte homeostasis is disturbed such as stroke, ischemic injury, inflammation, traumatic brain injury and hydrocephalus, cell volume regulation is challenged, sometimes past the point of recovery. Thus, a greater understanding of signaling pathways which regulate transport proteins as well as the functional and physical interactions that exist between transporters will provide a basis for the development of pharmaceutical targets to treat these prevalent and often devastating diseases.

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Section: Trpv4mentioning

confidence: 96%

Section: Trpv4mentioning

confidence: 99%

Channels and Transporters in Astrocyte Volume Regulation in Health and Disease

2022

Cell Physiol Biochem

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“…GSK1016790A significantly upregulated the expression of c-Fos, a marker of neuronal activity (Asao et al, 2020).…”

Section: Trpv4mentioning

confidence: 98%

“…Inhibition was completely reversed in TRPV4‐KO mice. GSK1016790A significantly upregulated the expression of c‐Fos, a marker of neuronal activity (Asao et al., 2020 ).…”

Section: Trpv Channelsmentioning

confidence: 99%

Transient receptor potential ion channels and cerebral stroke

Zou

Miao

et al. 2022

Brain and Behavior

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Methods:The databases Pubmed, and the National Library of Medicine were searched for literature. All papers on celebral stroke and transient receptor potential ion channels were considered.Results: Stroke is the second leading cause of death and disability, with an increasing incidence in developing countries. About 75 per cent of strokes are caused by occlusion of cerebral arteries, and substantial advances have been made in elucidating mechanisms how stroke affects the brain. Transient receptor potential (TRP) ion channels are calcium-permeable channels highly expressed in brain that drives Ca 2+ entry into multiple cellular compartments. TRPC1/3/4/6, TRPV1/2/4, and TRPM2/4/7 channels have been implicated in stroke pathophysiology. Conclusions:Although the precise mechanism of transient receptor potential ion channels in cerebral stroke is still unclear, it has the potential to be a therapeutic target for patients with stroke if developed appropriately. Hence, more research is needed to prove its efficacy in this context.

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“…As a cell surface-expressed, non-selective cation channel, TRPV4 can be activated by chemical, mechanical and osmotic stimuli via regulation of calcium ion influx ( 12 ). Notably, the inhibition of TRPV4 channel opening reportedly contributes to neuronal death and inflammatory response in a model of intracerebral hemorrhage ( 13 ), while activation of TRPV4 channel opening can participate in the regulation of neuronal excitability and behavior in mammals ( 14 ). Most importantly, it has been reported that silencing TRPV4 can block excessive ketamine-induced neurotoxic effects ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Ketamine administration ameliorates anesthesia and surgery‑induced cognitive dysfunction via activation of TRPV4 channel opening

Zhou

et al. 2022

Exp Ther Med

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Perioperative neurocognitive disorder (PND) is a common complication associated with anesthesia and surgery in the elderly. The dysfunction of transient receptor potential vanilloid 4 (TRPV4) has been associated with a number of diseases, including Alzheimer's disease. Given that ketamine can reportedly improve PNDs, the present study sought to determine whether ketamine-induced PND alleviation was mediated by activation of TRPV4 channel opening. A total of 120, 20-month-old male C57BL/6 mice were randomly divided into five groups: Vehicle, PND (tibial fracture surgery), PND + ketamine (Ket), PND + Ket + HC-067047 (HC), and PND + HC groups. Ketamine (0.5 mg/kg) was administered intraperitoneally once a day for 3 days after surgery and HC-067047 (1 µmol/2 µl), an antagonist of TRPV4, was administered via the left lateral ventricle 30 min before ketamine treatment. Superoxide dismutase (SOD), malondialdehyde (MDA), lipid peroxidation (LPO), IL-1β, IL-6, adenosine monophosphate-activated protein kinase (AMPK), NF-κB, TNF-α and IFN-β levels were determined 3 days after surgery. At 28 days after surgery, fear conditioning and novel object recognition were assessed, and Aβ1-42 levels were measured and ionized calcium binding adaptor molecule 1 (Iba1) staining was conducted on day 31 after surgery. The results revealed that ketamine administration upregulated total SOD activity, downregulated MDA and LPO content, mitigated phosphorylated (p)-NF-κB, TNF-α mRNA and IFN-β mRNA expression in the hippocampus, and promoted p-AMPK 3 days after surgery. Furthermore, it was found that ketamine increased both context- and tone-dependent fear conditioning, and the time spent exploring a novel object, and reduced Aβ peptide levels and microglial activation 30 days after surgery. Notably, these changes could be reversed by HC-067047 to a certain extent. In conclusion, ketamine improved PND in aged mice after tibial fracture surgery and the potential mechanism may involve activation of the TRPV4/AMPK/NF-κB signaling pathway.

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Transient receptor potential vanilloid 4 agonist GSK1016790A improves neurological outcomes after intracerebral hemorrhage in mice

Cited by 8 publications

References 26 publications

Channels and Transporters in Astrocyte Volume Regulation in Health and Disease

Channels and Transporters in Astrocyte Volume Regulation in Health and Disease

Transient receptor potential ion channels and cerebral stroke

Ketamine administration ameliorates anesthesia and surgery‑induced cognitive dysfunction via activation of TRPV4 channel opening

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