https://scholars.lib.ntu.edu.tw/handle/123456789/516732
標題: | Transcranial focused ultrasound pulsation suppresses pentylenetetrazol induced epilepsy in vivo | 作者: | SG Chen CH Tsai CJ Lin CC Lee HY Yu TH Hsieh HAO-LI LIU SG Chen CH Tsai CJ Lin CC Lee HY Yu TH Hsieh |
關鍵字: | Epilepsy; Focused ultrasound; mTOR phosphorylation; Transcranial | 公開日期: | 2020 | 卷: | 13 | 起(迄)頁: | 35-46 | 來源出版物: | Brain Stimulation | 摘要: | Background: Epilepsy is a neurological disorder characterized by abnormal neuron discharge, and one-third of epilepsy patients suffer from drug-resistant epilepsy (DRE). The current management for DRE includes epileptogenic lesion resection, disconnection, and neuromodulation. Neuromodulation is achieved through invasive electrical stimulus including deep brain stimulation, vagus nerve stimulation, or responsive neurostimulation (RNS). As an alternative therapy, transcranial focused ultrasound (FUS) can transcranially and non-invasively modulate neuron activity. Objective: This study seeks to verify the use of FUS pulsations to suppress spikes in an acute epileptic small-animal model, and to investigate possible biological mechanisms by which FUS pulsations interfere with epileptic neuronal activity. Methods: The study used a total of 76 Sprague-Dawley rats. For the epilepsy model, rats were administered pentylenetetrazol (PTZ) to induce acute epileptic-like abnormal neuron discharges, followed by FUS exposure. Various ultrasound parameters were set to test the epilepsy-suppressing effect, while concurrently monitoring and analyzing electroencephalogram (EEG) signals. Animal behavior was monitored and histological examinations were conducted to evaluate the hazard posed by ultrasound exposure and the expression of neuronal activity markers. Western blotting was used to evaluate the correlation between FUS-induced epileptic suppression and the PI3K-mTOR signaling pathway. Results: We observed that FUS pulsations effectively suppressed epileptic activity and observed EEG spectrum oscillations; the spike-suppressing effect depended on the selection of ultrasound parameters and highly correlated with FUS exposure level. Expression level changes of c-Fos and GAD65 were confirmed in the cortex and hippocampus, indicating that FUS pulsations deactivated excitatory cells and activated GABAergic terminals. No tissue damage, inflammatory response, or behavioral abnormalities were observed in rats treated with FUS under these exposure parameters. We also found that the FUS pulsations down-regulated the S6 phosphorylation and decreased pAKT expression. Conclusion: Our results suggest that pulsed FUS exposure effectively suppresses epileptic spikes in an acute epilepsy animal model, and finds that ultrasound pulsation interferes with neuronal activity and affects the PTZ-induced PI3K-Akt-mTOR pathway, which might help explain the mechanism underlying ultrasound-related epileptic spike control. © 2019 Elsevier Inc. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85072684331&doi=10.1016%2fj.brs.2019.09.011&partnerID=40&md5=988bc12620a72d58ca4ee26ca2b98266 | ISSN: | 1935861x | DOI: | 10.1016/j.brs.2019.09.011 | SDG/關鍵字: | glutamate decarboxylase 65; mammalian target of rapamycin; pentetrazole; phosphatidylinositol 3 kinase; protein c fos; protein kinase B; protein S6; pentetrazole; animal behavior; animal experiment; animal model; animal tissue; Article; brain cortex; brain depth stimulation; controlled study; down regulation; drug resistant epilepsy; electroencephalography; epileptic discharge; epileptic focus; hazard assessment; hippocampus; histology; in vivo study; male; mTOR signaling; nerve cell membrane potential; nonhuman; oscillation; pentylenetetrazole-induced seizure; priority journal; protein expression; protein expression level; protein phosphorylation; radiation exposure; radiation hazard; rat; reflex epilepsy; spike; transcranial focused ultrasound; ultrasound therapy; Western blotting; animal; epilepsy; heart rate; pathophysiology; physiology; procedures; Sprague Dawley rat; ultrasound therapy; Animals; Cerebral Cortex; Electroencephalography; Epilepsy; Heart Rate; Hippocampus; Male; Pentylenetetrazole; Rats; Rats, Sprague-Dawley; Ultrasonic Therapy |
顯示於: | 電機工程學系 |
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