Ultrasound stimulation inhibits recurrent seizures and improves behavioral outcome in an experimental model of mesial temporal lobe epilepsy
Hilola Hakimova, Sangwoo Kim, Kon Chu, Sang Kun Lee, Bumseok Jeong, Daejong Jeon
Epilepsy & Behavior 2015, 49, 26-32 · 10.1016/j.yebeh.2015.04.008
Abstract
Current therapies for epilepsy consist mostly of pharmacological agents or invasive surgery. Recently, ultrasound (US) stimulation has been considered a promising tool for the noninvasive treatment of brain diseases, including epilepsy. However, in temporal lobe epilepsy (TLE), a common form of epilepsy, neurophysiological and functional outcomes following US stimulation are not well defined. To address this, we developed a paradigm of transcranial pulsed US stimulation to efficiently suppress seizure activity in the initial/acute period in a kainate (KA)-induced mouse model of mesial TLE. Pulsed US stimulation inhibited acute seizure activity and either delayed the onset of or suppressed status epilepticus (SE). Kainate-treated mice that had received US stimulation in the initial period exhibited fewer spontaneous recurrent seizures (SRSs) and improved performance in behavioral tasks assessing sociability and depression in the chronic period of epilepsy. Our results demonstrate that US stimulation in the acute period of epilepsy can inhibit SRSs and improve behavioral outcomes in a mouse model of mesial TLE. The present study suggests that noninvasive transcranial pulsed US stimulation may be feasible as an adjuvant therapy in patients with epilepsy. This article is part of a Special Issue entitled "Status Epilepticus".
Abstract via europepmc.
Exposures
Exposure 1: Pulsed US to hippocampus (0.2 MHz)
Target: hippocampus — “hippocampus (transducer placed over the head just over the hippocampus, near the unilateral CA3 kainate injection site)”
Device: Ultran · Ultran Group ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 200 | ✓✓✓ |
| Pulse duration (ms) | 1 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 500 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 50% | |
| Sonication duration (s) | 30 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Ultrasound stimulation was delivered immediately after animals began to display ictal spikes on EEG and concomitant convulsive seizure behaviours (Racine stage 4, 5, or 6) following kainate microinjection into CA3. Each 30-s stimulation used a single 1-ms pulse (5 Vpp) containing 200 acoustic cycles (0.5 Vpp) at 0.2 MHz, repeated at a PRF of 0.5 kHz; a 19-mm-diameter transducer was coupled to the head with ultrasonic gel. The number of convulsive seizures before status epilepticus differed in each mouse (6 to 30), so the number of US stimulations differed per mouse; for behavioural studies, 30-s US stimulations (without EEG recording) were given each time convulsive seizures occurred.
Flags from extraction
n_subjects— Two separate ultrasound-exposed cohorts are reported without a combined total: n=7 mice with EEG recording (acute seizure/status-epilepticus experiment) and n=13 mice in the behaviour-only KA/US group (no EEG surgery).n_sessions_per_subject— The number of US stimulations per mouse varied with the number of convulsive seizures observed before status epilepticus, stated as ranging 'from 6 to 30' per mouse; no single fixed number of sessions is given.