Ultrasound modulates neuronal potassium currents via ionotropic glutamate receptors

Clennell, Benjamin; Steward, Tom G. J.; Hanman, Kaliya; Needham, Tom; Benachour, Janette; Jepson, Mark A.; Elley, Meg; Halford, Nathan; Heesom, Kate J; Shin, Eunju; Molnár, Elek; Drinkwater, Bruce W.; Whitcomb, Daniel J.

doi:10.1016/j.brs.2023.01.1674

Cited by 12 publications

(5 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To that point, it should be noted that in vitro results provide evidence for entirely vascular-independent components of persistent effects; Clennell et al (2021), for example, found that FUS can induce up to 8 hours of sustained enhanced excitability in cultured cortical neurons, possibly due to dephosphorylation of select subunits of voltage-gated potassium channels (i.e. K v 2.1) (Clennell et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

Label free, capillary-scale blood flow mappingin vivoreveals that low intensity focused ultrasound evokes persistent dilation in cortical microvasculature

Shen,

Jethe,

Hehir

et al. 2024

Preprint

View full text Add to dashboard Cite

Non-invasive, low intensity focused ultrasound (FUS) is an emerging neuromodulation technique that offers the potential for precision, personalized therapy. An increasing body of research has identified mechanosensitive ion channels that can be modulated by FUS and support acute electrical activity in neurons. However, neuromodulatory effects that persist from hours to days have also been reported. The brain's ability to provide targeted blood flow to electrically active regions involve a multitude of non-neuronal cell types and signaling pathways in the cerebral vasculature; an open question is whether persistent effects can be attributed, at least partly, to vascular mechanisms. Using a novel in vivo optical approach, we found that microvascular responses, unlike larger vessels which prior investigations have explored, exhibit persistent dilation. This finding and approach offers a heretofore unseen aspect of the effects of FUS in vivo and indicate that concurrent changes in neurovascular function may partially underly persistent neuromodulatory effects.

show abstract

Section: Discussionmentioning

confidence: 99%

Label free, capillary-scale blood flow mappingin vivoreveals that low intensity focused ultrasound evokes persistent dilation in cortical microvasculature

Shen,

Jethe,

Hehir

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Furthermore, ultrasonic stimuli can facilitate the regeneration and repair of damaged neurons and the creation of new neurons 3 . Ultrasonic stimulation triggers neuronal activity by activating the synaptic signal cascade 53 , resulting in increased excitatory synaptic transmission 54 , cortical excitability and neuroplasticity 55,56 . C-Fos, a protein widely used as a marker of neuronal activation [57][58][59] , was increased in the LITUS-treated CPR group, particularly in the cerebral cortex and amygdala region.…”

Section: Discussionmentioning

confidence: 99%

Low-intensity transcranial ultrasound (LITUS) exerts neuroprotective effects by modulating inflammatory responses via the Piezo1-Dkk3/Ca 2+ /PI3K-Akt signaling pathway

Xu,

Gu,

Liu

et al. 2024

Preprint

View full text Add to dashboard Cite

Background Post-cardiac arrest brain injury (PCABI) contributes to unfavorable outcomes following cardiopulmonary resuscitation (CPR) significantly, with effective therapeutic interventions for PCABI remain elusive. Low-intensity transcranial ultrasound (LITUS) has exhibited neuroprotective effects in various disease models, yet the precise mechanisms underlying these effects have not been fully elucidated. Consequently, the therapeutic potential of ultrasound stimuli in PCABI and the underlying mechanisms necessitate further exploration. Methods In vivo, a murine model of cardiac arrest (CA) was established and subjected to LITUS. Neurological function was assessed through behavioral tests and neurofunctional scoring. Hematoxylin and Eosin (HE) staining was employed to evaluate brain injury, while proteomic analysis was utilized to identify potential target proteins and pathways. Cells involved in pharmacological interventions or gene knockdown were subjected to oxygen/glucose deprivation/reoxygenation to mimic ischemia-reperfusion conditions in the brain. Protein-protein interactions were confirmed through co-immunoprecipitation. Intracellular calcium (Ca2+) influx was quantified using live-cell calcium imaging and flow cytometry. Cell viability was assessed using the Cell Counting Kit-8 (CCK8) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the expression of targeted genes. The expression of related proteins was detected through immunofluorescence and Western blotting assays. Results LITUS administration significantly improves 24-hour survival rates, promotes neurological function recovery, attenuates brain injury, and activates neurons in mice subjected to CPR. In vitro experiments revealed that ultrasound (US) mediates Ca2+ influx via the synergistic action of Piezo1 and Dkk3, thereby suppressing inflammatory responses, augmenting cell vitality, and promoting neuronal activation. These findings strongly indicate that the neuroprotective effects of LITUS may be mediated via the Piezo1-Dkk3/Ca2+/PI3K-Akt3 pathway. Conclusions This study firstly elucidates the neuroprotective effects of LITUS on PCABI and clarifies the potential mechanism. We posit that this study broadens the evidence base supporting future research into the application of LITUS in clinical PCABI patients.

show abstract

“…In this experiment, continuous therapeutic ultrasound was used, as this can provide a thermal effect, acting directly on tissue extensibility, reducing contractures and increasing local circulation (18,(24)(25)(26)(27). In addition to these, ultrasound is also an important anabolic stimulus, acting on changes in cellular ion flow (mainly related to calcium, which in this case has anabolic rather than catabolic effects, which is also one of its functions in skeletal muscle) (28)(29)(30)(31)(32)(33), resulting in, among other effects, a reduction in interleukin activity, an increase in the concentration of growth factors and protein synthesis, neovascularization and analgesia (27,(34)(35)(36)(37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Effect of Therapeutic Ultrasound on the Recovery of the Tibialis Anterior Muscle in Remobilized Wistar Rats after a Period of Immobilization: An Analysis Using the Pathological Index

Kufner Meassi,

de Souza Oliveira,

Pedroso de Oliveira

et al. 2024

Muscle Ligaments and Tendons J

View full text Add to dashboard Cite

Ultrasound modulates neuronal potassium currents via ionotropic glutamate receptors

Cited by 12 publications

References 62 publications

Label free, capillary-scale blood flow mappingin vivoreveals that low intensity focused ultrasound evokes persistent dilation in cortical microvasculature

Label free, capillary-scale blood flow mappingin vivoreveals that low intensity focused ultrasound evokes persistent dilation in cortical microvasculature

Low-intensity transcranial ultrasound (LITUS) exerts neuroprotective effects by modulating inflammatory responses via the Piezo1-Dkk3/Ca 2+ /PI3K-Akt signaling pathway

Effect of Therapeutic Ultrasound on the Recovery of the Tibialis Anterior Muscle in Remobilized Wistar Rats after a Period of Immobilization: An Analysis Using the Pathological Index

Contact Info

Product

Resources

About