Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation.

Microglia are important players in surveillance and repair of the brain. Implanting an electrode into the cortex activates microglia, produces an inflammatory cascade, triggers the foreign body response, and opens the blood-brain barrier. These changes can impede intracortical brain-computer interfaces performance. Using two-photon imaging of implanted microelectrodes, we test the hypothesis that low-intensity pulsed ultrasound stimulation can reduce microglia-mediated neuroinflammation following the implantation of microelectrodes. In the first week of treatment, we found that low-intensity pulsed ultrasound stimulation increased microglia migration speed by 128%, enhanced microglia expansion area by 109%, and a reduction in microglial activation by 17%, indicating improved tissue healing and surveillance. Microglial coverage of the microelectrode was reduced by 50% and astrocytic scarring by 36% resulting in an increase in recording performance at chronic time. The data indicate that low-intensity pulsed ultrasound stimulation helps reduce the foreign body response around chronic intracortical microelectrodes.

Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation.

Microglia are important players in surveillance and repair of the brain. Their activation mediates neuroinflammation caused by intracortical microelectrode implantation, which impedes the application of intracortical brain-computer interfaces (BCIs). While low-intensity pulsed ultrasound stimulation (LIPUS) can attenuate microglial activation, its potential to modulate the microglia-mediated neuroinflammation and enhance the bio-integration of microelectrodes remains insufficiently explored. We found that LIPUS increased microglia migration speed from 0.59±0.04 to 1.35±0.07 µm/hr on day 1 and enhanced microglia expansion area from 44.50±6.86 to 93.15±8.77 µm 2 /min on day 7, indicating improved tissue healing and surveillance. Furthermore, LIPUS reduced microglial activation by 17% on day 6, vessel-associated microglia ratio from 70.67±6.15 to 40.43±3.87% on day 7, and vessel diameter by 20% on day 28. Additionally, microglial coverage of the microelectrode was reduced by 50% in week 1, indicating better tissue-microelectrode integration. These data reveal that LIPUS helps resolve neuroinflammation around chronic intracortical microelectrodes.

Transdermal Delivery of Enfuvirtide in a Porcine Model Using a Low-Frequency, Low-Power Ultrasound Transducer Patch.

Ultrasound-mediated transdermal delivery is a promising parenteral administration method for large-molecule or unstable medications. This study evaluated skin health and systemic delivery when administering enfuvirtide, an injectable anti-retroviral medication, over a 1-mo period in a porcine model using a low-frequency cymbal transducer. Three groups received twice-daily treatments: (i) enfuvirtide injection control (n = 12); (ii) saline ultrasound control (n = 6); and (iii) enfuvirtide ultrasound treatment (n = 13). Ultrasound parameters were as follows: 30-min exposure, 90 mW/cm², 24-26 kHz and 15% duty cycle. No statistical difference in trans-epidermal water loss, a measure of skin health and function, was seen between ultrasound-treated and control skin sites for either saline (p = 0.50) or enfuvirtide (p = 0.29) groups. Average trough plasma concentrations of enfuvirtide were 0.6 ± 0.2 and 2.8 ± 0.8 µg/mL for ultrasound and injection, respectively. Tolerability and efficacy results indicate that chronic, low-frequency ultrasound exposure can be a practical means for transdermal delivery of medications such as enfuvirtide.

Effects of Axial Vibration on Needle Insertion into the Tail Veins of Rats and Subsequent Serial Blood Corticosterone Levels.

Blood collection is commonplace in biomedical research. Obtaining sufficient sample while minimizing animal stress requires significant skill and practice. Repeated needle punctures can cause discomfort and lead to variable release of stress hormones, potentially confounding analysis. We designed a handheld device to reduce the force necessary for needle insertion by using low-frequency, axial (forward and backward) micromotions (that is, vibration) delivered to the needle during venipuncture. Tests with cadaver rat-tail segments (n = 18) confirmed that peak insertion forces were reduced by 73% on average with needle vibration. A serial blood-sampling study was then conducted by using Sprague-Dawley rats divided into 2 groups based on needle condition used to cause bleeds: vibration on (n = 10) and vibration off (n = 9). On 3 days (1 wk apart), 3 tail-vein blood collections were performed in each subject at 1-h intervals. To evaluate associated stress levels, plasma corticosterone concentration was quantified by radioimmunoassay and behavior (that is, movement and vocalization) was scored by blinded review of blood-sampling videos. After the initial trial, average corticosterone was lower (46% difference), the mean intrasubject variance trended lower (72%), and behavioral indications of stress were rated lower for the vibration-on group compared with the vibration-off group. Adding controlled vibrations to needles during insertion may decrease the stress associated with blood sampling from rats--an important methodologic advance for investigators studying and assessing stress processes and a refinement over current blood sampling techniques.

Bizzy Break! The effect of a classroom-based activity break on in-school physical activity levels of primary school children.

The school has been identified as a key setting to promote physical activity. The purpose of this study was to evaluate the effect of a classroom-based activity break on in-school step counts of primary school children. Data for 90 children (49 boys, 41 girls, 9.3 ± 1.4 years) from three Irish primary schools is presented. In each school one class was randomly assigned as the intervention group and another as controls. Children's step counts were measured for five consecutive days during school hours at baseline and follow-up. Teachers of the intervention classes led a 10 min activity break in the classroom each day (Bizzy Break!). Mean daily in-school steps for the intervention at baseline and follow-up were 5351 and 5054. Corresponding values for the control group were 5469 and 4246. There was a significant difference in the change in daily steps from baseline to follow-up between groups (p < .05). There was no evidence that girls and boys responded differently to the intervention (p > .05). Children participating in a daily 10 min classroom-based activity break undertake more physical activity during school hours than controls.