Low-intensity ultrasound suppresses low-Mg 2+ -induced epileptiform discharges in juvenile mouse hippocampal slices
Zhen Zhang, Weibao Qiu, Haiqing Gong, Guofeng Li, Qiuju Jiang, Peiji Liang, Hairong Zheng, Puming Zhang
Journal of Neural Engineering 2019, 16, 036006 · 10.1088/1741-2552/ab0b9a
Abstract
Objective It has been shown that low-intensity ultrasound (LIUS) can suppress seizures in some laboratory studies. However, the mechanism of the suppression effect of LIUS remains unclear. The goal of this study is to investigate the modulation effects of focused LIUS on epileptiform discharges in mouse hippocampal slices as well as the underlying mechanism. Approach Epileptiform discharges in hippocampal slices of 8 d-old mice were induced by low-Mg 2+ artificial cerebrospinal fluid and recorded by a micro-electrode array in vitro. LIUS was delivered to hippocampal slices to investigate its modulation effects on epileptiform discharges. Pharmacological experiments were conducted to study the mechanism of the modulation effects. Main results LIUS suppressed the amplitude, rate and duration of ictal discharges. For inter-ictal discharges, LIUS suppressed the amplitude but facilitated the rate. LIUS suppressed the spontaneous spiking activities of pyramidal neurons in CA3, and the suppression effect was eliminated by Kaliotoxin. The suppression effect of LIUS on epileptiform discharges was weakened when the perfusion was mixed with Kaliotoxin. Significance Those findings demonstrate that LIUS suppresses the epileptiform discharges in 8 d-old mouse hippocampal slices and that its suppression effect can mainly attributed to the activation of mechanosensitive Kv1.1 channels.
Abstract via europepmc.
Exposures
Exposure 1: Focused low-intensity ultrasound (LIUS) applied to hippocampal slice
Target: hippocampal formation — “hippocampal slice (CA3, CA1, dentate gyrus, and subiculum)”
Device: Olympus / Panametrics · Olympus NDT · A314S ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 0.4 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 2,000 | ✓✓✓⚑ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 80% | |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | 119 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 0.0078, 0.0709, 0.126swept | ✓✓✓ |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | ⚑ |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable |
Sonication parameters: sonication duration (SD) = 1 s, inter-stimulus interval (ISI) = 3 s, tone burst duration (TBD) = 0.4 ms, pulse repetition period (PRP) = 0.5 ms, repeated for a total LIUS administration period of 900 s (15 min) per slice.
Flags from extraction
n_subjects— Different sub-analyses report different slice counts (e.g. n=10 for main suppression statistics, n=18 for CA3 VPT analysis, n=5 for KTX pharmacology); no single total number of slices/mice used in the whole study is stated.exposures[0].timing.pulse_repetition_frequency_hz— Paper states pulse repetition PERIOD (PRP=0.5 ms) rather than PRF directly; converted via PRF=1/PRP (unit conversion of a stated period, per instructions).exposures[0].in_situ.pressure_kpa— Values described as 'in hippocampal slice' were derived from a hydrophone scan of the free field mapped onto the expected slice position, not a measurement through/within intact tissue; classified as in_situ based on the paper's own wording ('in hippocampal slice') but flagged for domain ambiguity.