Sonoporation is a targeted drug delivery technique that employs cavitation microbubbles to generate transient pores in the cell membrane, allowing foreign substances to enter cells by passing through the pores. Due to the broad size distribution of microbubbles, cavitation events appear to be a random process, making it difficult to achieve controllable and efficient sonoporation. In this work a technique is reported using a microfluidic device that enables in parallel modulation of membrane permeability by an oscillating microbubble array. Multirectangular channels of uniform size are created at the sidewall to generate an array of monodispersed microbubbles, which oscillate with almost the same amplitude and resonant frequency, ensuring homogeneous sonoporation with high efficacy. Stable harmonic and high harmonic signals emitted by individual oscillating microbubbles are detected by a laser Doppler vibrometer, which indicates stable cavitation occurred. Under the influence of the acoustic radiation forces induced by the oscillating microbubble, single cells can be trapped at an oscillating microbubble surface. The sonoporation of single cells is directly influenced by the individual oscillating microbubble. The parallel sonoporation of multiple cells is achieved with an efficiency of 96.6 ± 1.74% at an acoustic pressure as low as 41.7 kPa.

Objective: Low-frequency low-intensity pulsed ultrasound (LIPUS) has emerged as a non-invasive neuromodulation tool. The aim of this study is to examine whether LIPUS stimulation of the motor cortex can improve parkinsonian motor deficit in a mouse model induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Methods: Acute Parkinson's disease (PD) mouse model is built by injection of MPTP (20 mg/kg) every 4 h in a total of four doses in one day. Mice are randomized into control, MPTP, sham-LIPUS+MPTP, and LIPUS+MPTP group. For LIPUS+MPTP group, 7 days of LIPUS (800 kHz, 10% duty cycle, 100-Hz pulse repetition frequency, 40 min/day) is delivered to the motor cortex. An open field test (OFT) is conducted on day 4 and a pole test on day 5, respectively. Striatal total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) are measured on day 8. The safety of LIPUS is verified using Hematoxylin and esosin (HE) staining and Nissl staining. Results: LIPUS treatment improves rearing number in the OFT on day 4 (n = 8, p = 0.037) and locomotor activity in the pole test on day 5 (n = 8, p = 0.007) compared with the sham-LIPUS+MPTP group. Moreover, LIPUS increases T-SOD (n = 7, p = 0.006) and GSH-PX (n = 7, p = 0.030) compared with the sham-LIPUS+MPTP group. In addition, HE and Nissl staining shows no brain tissue injury induced by LIPUS. Conclusion: These findings demonstrate that LIPUS may have neuromodulation effects in PD mice. Significance: LIPUS may provide a novel neuromodulation tool for PD treatment.

This paper presents quantitative analysis of blood flow shear stress by measuring the carotid arterial wall shear stress (WSS) and the intima-media thickness (IMT) of experimental rabbits fed with high-fat feedstuff on a weekly basis in order to cause atherosclerosis. This study is based on establishing an atherosclerosis model of high-fat rabbits, and measuring the rabbits’ common carotid arterial WSS of the experimental group and control group on a weekly basis. Detailed analysis was performed by using WSS quantification. We have demonstrated small significant difference of rabbit carotid artery WSS between the experimental group and the control group (P<0.01) from the 1st week onwards, while the IMT of experimental group had larger differences from 5th week compared with the control group (P<0.05). Next, we have shown that with increasing blood lipids, the rabbit carotid artery shear stress decreases and the rabbit carotid artery IMT goes up. The decrease of shear stress appears before the start of IMT growth. Furthermore, our receiver operator characteristic (ROC) curve analysis showed that when the mean value of shear stress is 1.198 dyne/cm2, the rabbit common carotid atherosclerosis fatty streaks sensitivity is 89.8%, and the specificity is 81.3%. The area under the ROC curve is 0.9283. All these data goes to show that WSS decreasing to 1.198 dyne/cm2 can be used as an indicator that rabbit common carotid artery comes into the period of fibrous plaques. In conclusion, our study is able to find and confirm that the decrease of the arterial WSS can predict the occurrence of atherosclerosis earlier, and offer help for positive clinical intervention.

Ultrasound stimulation has recently emerged as a non-invasive method for modulating brain activity in animal and human studies with healthy subjects. Whether brain diseases such as Alzheimer's disease, epilepsy, and depression can be treated using ultrasound stimulation still needs to be explored. Recent studies have reported that ultrasound stimulation suppressed epileptic seizures in a rodent model of epilepsy. These findings raise the crucial question of whether ultrasound stimulation can inhibit seizures in non-human primates with epilepsy. Here, we addressed this critical question. We confirmed that ultrasound stimulation significantly reduced the frequency of seizures in acute epileptic monkeys. Furthermore, the results showed that the number and duration of seizures were reduced, whereas the inter-seizure interval was increased after ultrasound stimulation. Besides, no significant brain tissue damage was observed by T2-weighted MR imaging. Our results are of great importance for future clinical applications of ultrasound neuromodulation in patients with epilepsy.

Objective: Neuroinflammation contributes to the development and progression of Parkinson's disease (PD). The aim of this study was to examine whether ultrasound (US) stimulation of the subthalamic nucleus (STN) could suppress the neuroinflammation in a chronic PD mouse model induced by 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Methods: A chronic PD mouse model was built by injections of 20mg/kg MPTP and 250 mg/kg probenecid at 3.5-day intervals for 5 weeks. Mice were randomized into control+sham, MPTP+sham and MPTP+STN+US group. For MPTP+STN+US group, ultrasound wave (3.8 MHz, 50% duty cycle, 1 kHz pulse repetition frequency, 30 min/day) was delivered to the STN the day after MPTP and probenecid injection (the early stage of PD progression). The rotarod test and pole test were performed to evaluate the behavioral changes after ultrasound treatment. Then, the activity of microglia and astrocyte were measured to evaluate the inflammation level in the brain. Results: Ultrasound stimulation improved the latency to falls in the rotarod test (p = 0.033) and decreased the climbing time in the pole test (p = 0.016) compared with MPTP+sham group. Moreover, ultrasound stimulation reduced the chronic inflammation response as shown in microglia (p = 0.007) and astrocyte (p = 0.032) activation. In addition, HE, Nissl and Tunel staining showed that no brain tissue injury was induced by US. Conclusion: These findings demonstrated that ultrasound stimulation could suppress neuroinflammation in PD mice. Significance: Transcranial ultrasound neuromodulation offers a novel approach for Parkinson's disease intervention, potentially through its anti-neuroinflammation functions.

Plasticity of synaptic structure and function play an essential role in neuronal development, cognitive functions, and degenerative diseases. Recently, low-intensity pulsed ultrasound (LIPUS) stimulation has been reported as a promising technology for neuromodulation. However, the effect of LIPUS stimulation on the structural and functional synaptic plasticity in rat hippocampus has not yet been addressed. The aim of this study was to investigate whether LIPUS stimulation could affect the dendritic structure, electrophysiological properties, and expression level of glutamate receptors GluN2A, GluN2B, and GluR1 subunits in rat hippocampus. Transcranial LIPUS was delivered to CA1 of the intact hippocampus of rats ( n = 40 ) for 10 days (10 min/day) with the following parameters: fundamental frequency of 0.5 MHz, pulse repetition frequency (PRF) of 500 Hz, peak negative pressure of 0.42 MPa, and Ispta of 360 mW/cm2. The effect of LIPUS on dendritic structure, electrophysiological properties, and the expression of neurotransmitter receptors was measured using Golgi staining, electrophysiological recording, and western blotting, respectively. Golgi staining and electrophysiological recordings showed that LIPUS stimulation significantly increased the density of dendritic spines (0.72 ± 0.17 versus 0.94 ± 0.19 spines/ [Formula: see text], ) and the frequency of spontaneous excitatory postsynaptic current (0.37 ± 0.14 versus 1.77 ± 0.37 Hz, ) of CA1 hippocampal neurons. Furthermore, the western blotting analysis demonstrated a significant increase in the expression level of GluN2A ( ). The results illustrated the effect of LIPUS on the dendritic structure, function, and neurotransmitter receptors, which may provide a powerful tool for treating neurodegenerative diseases.