Temperature elevation in epileptogenic foci exacerbates epileptic discharge through TRPV4 activation

Shibasaki, Kazuo; Yamada, Katsuya; Miwa, Hideki; Yanagawa, Yuchio; Suzuki, Michiyasu; Tominaga, Makoto; Ishizaki, Yasuki

doi:10.1038/s41374-019-0335-5

Cited by 25 publications

(21 citation statements)

References 48 publications

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“…Indeed, TRPV4 may contribute to disease progression of epilepsy [59]. Epileptogenic foci possess elevated temperatures compared to healthy brain regions, and this activates TRPV4 channels.…”

Section: Discussionmentioning

confidence: 99%

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A multimodal, implantable sensor array and measurement system to investigate the suppression of focal epileptic seizure using hypothermia

et al. 2021

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Objective. Local cooling of the brain as a therapeutic intervention is a promising alternative for patients with epilepsy who do not respond to medication. In vitro and in vivo studies have demonstrated the seizure-suppressing effect of local cooling in various animal models. In our work, focal brain cooling in a bicuculline induced epilepsy model in rats is demonstrated and evaluated using a multimodal micro-electrocorticography (microECoG) device.Approach. We designed and experimentally tested a novel polyimide-based sensor array capable of recording microECoG and temperature signals concurrently from the cortical surface of rats.The effect of cortical cooling after seizure onset was evaluated using 32 electrophysiological sites and 8 temperature sensing elements covering the brain hemisphere, where injection of the epileptic drug was performed. The focal cooling of the cortex right above the injection site was accomplished using a miniaturized Peltier chip combined with a heat pipe to transfer heat. Control of cooling and collection of sensor data was provided by a custom designed Arduino based electronic board. We tested the experimental setup using an agar gel model in vitro, and then in vivo in Wistar rats.Main results. Spatial variation of temperature during the Peltier controlled cooling was evaluated through calibrated, on-chip platinum temperature sensors. We found that frequency of epileptic discharges was not substantially reduced by cooling the cortical surface to 30 °C, but was suppressed efficiently at temperature values around 20 °C. The multimodal array revealed that seizure-like ictal events far from the focus and not exposed to high drop in temperature can be also inhibited at an extent like the directly cooled area.Significance. Our results imply that not only the absolute drop in temperature determines the efficacy of seizure suppression, and distant cortical areas not directly cooled can be influenced.

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Section: Discussionmentioning

confidence: 99%

“…This was illustrated by wild type mice having greater epileptic EEG activity than TRPV4 knockout mice [59].…”

Section: Discussionmentioning

confidence: 99%

A multimodal, implantable sensor array and measurement system to investigate the suppression of focal epileptic seizure using hypothermia

et al. 2021

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“…It has been shown that 0.2° to 2°C changes in brain temperature significantly affect brain functions and neuronal properties ( 8 ). Furthermore, we found that 1°C hyperthermia could exacerbate epilepsy in vivo through the TRPV4 overactivation ( 26 ). Thus, we speculate that such a seemingly small temperature change increases TRPV4 activity and affects physiological responses in vivo.…”

Section: Discussionmentioning

confidence: 99%

Thermosensitive receptors in neural stem cells link stress-induced hyperthermia to impaired neurogenesis via microglial engulfment

et al. 2021

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“…2018), brain (Shibasaki et al . 2020) and the urinary bladder, has been reported. With significant changes in bladder functions noted in TRPV4 deficient mice (Gevaert et al .…”

Section: Introductionmentioning

confidence: 99%

“…arachidonic acid metabolites such as 5,6-epoxyeicosatrienoic acid) stimuli (Garcia-Elias et al 2014). Distribution of TRPV4 in various tissues, such as airway (Palaniyandi et al 2020), heart (Adapala et al 2020), skin (Szabo et al 2019), intestine (Huang et al 2018), brain (Shibasaki et al 2020) and the urinary bladder, has been reported. With significant changes in bladder functions noted in TRPV4 deficient mice (Gevaert et al 2007), there has been a growing interest in TRPV4 as a therapeutic target for bladder dysfunctions.…”

Section: Introductionmentioning

confidence: 99%

Emerging roles of the TRPV4 channel in bladder physiology and dysfunction

et al. 2020

The Journal of Physiology

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The transient receptor potential vanilloid type 4, TRPV4, is a polymodal cation channel which can be activated by diverse stimuli including mechanical, thermal and chemical cues. In the urinary bladder, TRPV4 is not only abundantly expressed in the urothelium but may also be localized in subepithelium, detrusor smooth muscles and afferent neurons. Emerging evidence indicates that the TRPV4 channel plays a sensory role in the uroepithelium, where it may regulate Yanyuan Wu graduated from Wenzhou Medical University with Bachelor's degree in Clinical Medicine. She is currently a PhD student in Shanghai Jiaotong University School of Medicine, jointly supervised by Professor Jun Qi (a Clinical Urologist) and Professor Weifang Rong (a basic scientist with a research interest in bladder physiology and dysfunction). Her current research focuses on ion channels and receptors in hypersensitive bladder.

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Temperature elevation in epileptogenic foci exacerbates epileptic discharge through TRPV4 activation

Cited by 25 publications

References 48 publications

A multimodal, implantable sensor array and measurement system to investigate the suppression of focal epileptic seizure using hypothermia

A multimodal, implantable sensor array and measurement system to investigate the suppression of focal epileptic seizure using hypothermia

Thermosensitive receptors in neural stem cells link stress-induced hyperthermia to impaired neurogenesis via microglial engulfment

Emerging roles of the TRPV4 channel in bladder physiology and dysfunction

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