Low-intensity transcranial ultrasound stimulation modulates neural activities in mice under propofol anaesthesia.

BACKGROUND: Previous studies have reported that transcranial focused ultrasound stimulation can significantly decrease the time to emergence from intraperitoneal ketamine-xylazine anaesthesia in rats. However, how transcranial focused ultrasound stimulation modulates neural activity in anaesthetized rats is unclear. METHODS: In this study, to answer this question, we used low-intensity transcranial ultrasound stimulation (TUS) to stimulate the brain tissue of propofol-anaesthetized mice, recorded local field potentials (LFPs) in the mouse motor cortex and electromyography (EMG) signals from the mouse neck, and analysed the emergence and recovery time, mean absolute power, relative power and entropy of local field potentials. RESULTS: We found that the time to emergence from anaesthesia in the TUS group (20.3 ± 1.7 min) was significantly less than that in the Sham group (32 ± 2.6 min). We also found that compared with the Sham group, 20 min after low-intensity TUS during recovery from anaesthesia, (1) the absolute power of local field potentials in mice was significantly reduced in the [1-4 Hz] and [13-30 Hz] frequency bands and significantly increased in the [55-100 Hz], [100-140 Hz] and [140-200 Hz] frequency bands; (2) the relative power of local field potentials in mice was enhanced at [30-45 Hz], [100-140 Hz] and [140-200 Hz] frequency bands; (3) the entropy of local field potentials ([1-200 Hz]) was increased. CONCLUSION: These results demonstrate that low-intensity TUS can effectively modulate neural activities in both awake and anaesthetized mice and has a positive effect on recovery from propofol anaesthesia in mice.

Transcranial low-intensity ultrasound stimulation for treating central nervous system disorders: A promising therapeutic application.

Transcranial ultrasound stimulation is a neurostimulation technique that has gradually attracted the attention of researchers, especially as a potential therapy for neurological disorders, because of its high spatial resolution, its good penetration depth, and its non-invasiveness. Ultrasound can be categorized as high-intensity and low-intensity based on the intensity of its acoustic wave. High-intensity ultrasound can be used for thermal ablation by taking advantage of its high-energy characteristics. Low-intensity ultrasound, which produces low energy, can be used as a means to regulate the nervous system. The present review describes the current status of research on low-intensity transcranial ultrasound stimulation (LITUS) in the treatment of neurological disorders, such as epilepsy, essential tremor, depression, Parkinson's disease (PD), and Alzheimer's disease (AD). This review summarizes preclinical and clinical studies using LITUS to treat the aforementioned neurological disorders and discusses their underlying mechanisms.

Neuroprotective effects of low-intensity transcranial ultrasound stimulation combined with Baicalin intervention on traumatic brain injury in animals.

Low-intensity transcranial ultrasound stimulation (LITUS) can improve the inflammatory reaction after traumatic brain injury (TBI), and Baicalin also has a good protective effect on TBI. The purpose of this study was to observe the neuroprotective effect of LITUS combined with Baicalin intervention in the TBI rats. Sprague Dawley (SD) rats were randomly divided into 5 groups (n = 15) which were Sham control group, TBI group, LITUS group, Baicalin group, LITUS combined with Baicalin group (LB group). The rats were scanned with 3.0 T magnetic resonance imager, and the apparent diffusion coefficient (ADC) and the fractional anisotropy (FA) of the brain injury cortical area were determined at 3 h, 1, 3, 7 and 10 d after TBI. The ADC value, FA value, neurological function score and Nissl staining were used to assess the level of brain damage of rats. The results showed that on the 10th day after TBI, the ADC values of the TBI group, the LITUS group and the Baicalin group were remarkable greater than that of the L-B group (all adjusted P < 0.05), FA values were remarkable smaller than that of the L-B group (all adjusted P < 0.05), neurological function scores were remarkable greater than that of the L-B group (all adjusted P < 0.05), and Nissl body loss rates were remarkable greater than that of the L-B group (all adjusted P < 0.001). This study indicated that compared with the LITUS group and the Baicalin group, the L-B group can more effectively reduce level of brain damage after TBI, and the method of LITUS combined with Baicalin intervention was a more effective neuroprotection for brain injury.

Effect of Low Intensity Transcranial Ultrasound Stimulation on Neuromodulation in Animals and Humans: An Updated Systematic Review.

Background: Although low-intensity transcranial ultrasound stimulation (LI-TUS) has received more recognition for its neuromodulation potential, there remains a crucial knowledge gap regarding the neuromodulatory effects of LI-TUS and its potential for translation as a therapeutic tool in humans. Objective: In this review, we summarized the findings reported by recently published studies regarding the effect of LI-TUS on neuromodulation in both animals and humans. We also aim to identify challenges and opportunities for the translation process. Methods: A literature search of PubMed, Medline, EMBASE, and Web of Science was performed from January 2019 to June 2020 with the following keywords and Boolean operators: [transcranial ultrasound OR transcranial focused ultrasound OR ultrasound stimulation] AND [neuromodulation]. The methodological quality of the animal studies was assessed by the SYRCLE's risk of bias tool, and the quality of human studies was evaluated by the PEDro score and the NIH quality assessment tool. Results: After applying the inclusion and exclusion criteria, a total of 26 manuscripts (24 animal studies and two human studies) out of 508 reports were included in this systematic review. Although both inhibitory (10 studies) and excitatory (16 studies) effects of LI-TUS were observed in animal studies, only inhibitory effects have been reported in primates (five studies) and human subjects (two studies). The ultrasonic parameters used in animal and human studies are different. The SYRCLE quality score ranged from 25 to 43%, with a majority of the low scores related to performance and detection bias. The two human studies received high PEDro scores (9/10). Conclusion: LI-TUS appears to be capable of targeting both superficial and deep cerebral structures to modulate cognitive or motor behavior in both animals and humans. Further human studies are needed to more precisely define the effective modulation parameters and thereby translate this brain modulatory tool into the clinic.

Neuroprotective effect of low-intensity transcranial ultrasound stimulation in endothelin-1-induced middle cerebral artery occlusion in rats.

BACKGROUND: Ischemic stroke is one of the leading causes of death and disability worldwide. Low-intensity transcranial ultrasound stimulation (LITUS) is a promising neuroprotective treatment for ischemic stroke. Diffusion-weighted imaging (DWI) can be highly sensitive in the detection of ischemic brain injury. Relative apparent diffusion coefficient (rADC) values can be used to evaluate the effect of LITUS on ischemic stroke. PURPOSE: The aim of this study was to determine the neuroprotective effect of LITUS at different time points using endothelin-1-induced middle cerebral artery occlusion in rats as a model of ischemic stroke. METHODS: Endothelin-1 (ET-1) was injected into the cerebral parenchyma near the middle cerebral artery, which induced focal, reversible, low-flow ischemia in rats. After occlusion of the middle cerebral artery for 30 min, 120 min, and 240 min, LITUS stimulation was used respectively. DWI was performed at 1, 3, 6, 12, 18, 24, 48, and 72 h after ischemia using a 3 T scanner. The rADC values were calculated, and functional outcomes assessed using neurobehavioral scores after ischemia. Nissl staining and estimation of Na+-K+-ATPase activity were used to assess the neuropathology after completing the last Magnetic Resonance Imaging (MRI) examination. RESULTS: Endothelin-1-induced occlusion of the middle cerebral artery resulted in significant dysfunction and neuronal damage in rats. Rats that received LITUS exhibited reduced damage of the affected brain tissue after cerebral ischemia. The greatest protective effect was found when LITUS stimulation occurred 30 min after cerebral ischemia. CONCLUSIONS: Imaging, behavioral, and histological results suggested that LITUS stimulation after an ischemic stroke produced significant neuroprotective effects.