Bidirectional Neuronal Control of Epileptiform Activity by Repetitive Transcranial Focused Ultrasound Stimulations.

Repetitive stimulation procedures are used in neuromodulation techniques to induce persistent excitatory or inhibitory brain activity. The directivity of modulation is empirically regulated by modifying the stimulation length, interval, and strength. However, bidirectional neuronal modulations using ultrasound stimulations are rarely reported. This study presents bidirectional control of epileptiform activities with repetitive transcranial-focused ultrasound stimulations in a rat model of drug-induced acute epilepsy. It is found that repeated transmission of elongated (40 s), ultra-low pressure (0.25 MPa) ultrasound can fully suppress epileptic activities in electro-encephalography and cerebral blood volume measurements, while the change in bursting intervals from 40 to 20 s worsens epileptic activities even with the same burst length. Furthermore, the suppression induced by 40 s long bursts is transformed to excitatory states by a subsequent transmission. Bidirectional modulation of epileptic seizures with repeated ultrasound stimulation is achieved by regulating the changes in glutamate and γ-Aminobutyric acid levels, as confirmed by measurements of expressed c-Fos and GAD65 and multitemporal analysis of neurotransmitters in the interstitial fluid obtained via microdialysis.

Therapeutic Quadrisected Annular Array for Improving Magnetic Resonance Compatibility.

OBJECTIVE: Focused ultrasound has been applied in brain therapeutics. Although focusing ultrasonic beams on multiple arbitrary regions under the guidance of magnetic resonance imaging(MRI) is needed for precise treatments, current therapeutic transducers with large pitch sizes have been optimized to focus on deep brain regions. While annular arrays can adjust the beam foci from cortical to deep regions, their circular shape may generate eddy current-induced magnetic flux during MRI. In this study, a quadrisected annular array is proposed to address these limitations. METHODS: Conventional and quadrisected annular arrays with three elements were implemented by loading the electrode patterns onto an 850 kHz 1-3 composite PZT disc, with a diameter of 31 mm, including three rings. MR compatibilities were demonstrated by imaging an MRI phantom with pulse sequences for B0 and B1 mapping and spin-echo imaging. Acoustic beam profiles, with and without a macaque monkey skull, were measured. A quadrisected transducer was also used to open the blood-brain barrier(BBB). RESULTS: The flip angle distortion improved by 20% in spin-echo MR imaging. The acoustic beam distortions shifting the focal point from 36 to 41mm and elongating the focal zone from 10 to 15 mm could be recovered to nearly the original values. BBB openings in the hippocampus and basal region were also demonstrated. CONCLUSION: The MR compatibility was improved by the increased resistance of the electrodes in the quadrisected array maintaining dynamic focusing capabilities. SIGNIFICANCE: The quadrisected annular design can be a fundamental structure for a larger MR-compatible segmented array transducer generating multiple acoustic foci.

Visibility of Bioresorbable Vascular Scaffold in Intravascular Ultrasound Imaging.

Bioresorbable vascular scaffold (BVS) has recently been spotlighted for its unique characteristics of absorbing into blood vessels and eventually disappearing. Although intravascular ultrasound (IVUS) is the most common guiding tool for stent deployment, the echogenicity of BVS struts has changed as the center of stent lumen and scanning rotation is not concentric, which may cause a critical erroneous measurement in practice. This study investigated the physical conditions for dimming the stent brightness in IVUS images using a finite-difference method (FDM) to numerically solve acoustic wave propagation through nonhomogeneous medium. The dimmed brightness is caused by an angled rectangular cross section of a strut and its similar acoustic impedance with water. Imaging frequency is not a major cause. However, the angle between the acoustic beam and the BVS surface is the major cause of the dimmed brightness. As a solution, an approach using a frequency compounding method with signal polarity comparator was proposed to recover the reduced brightness without sacrificing spatial resolutions. Based on the simulation study, the signal level from BVS can be attenuated down by 17 dB when the angle between the acoustic beamline and the surface of BVS is more than 45°. With the proposed frequency compounding approach, the reduced signal can be recovered by 6 dB. In the experimental BVS IVUS imaging, strut brightness was reduced by 18 dB with an angled strut position and recovered by 5 dB with the proposed frequency compounding method. A pig coronary was imaged to demonstrate the performance of the proposed method.

A Soft Housing Needle Ultrasonic Transducer for Focal Stimulation to Small Animal Brain.

Conventional acoustic brain stimulators that transmit low frequency (< 1 MHz) bursts in a pulse repetition frequency with large-sized transducers are barely compatible with small animal models because of broad beam width, possible stimulation of auditory pathways, and blocking of field-of-view for in vivo imaging of brain hemodynamics and neuronal activities. A miniaturized ultrasound stimulator with higher stimulation frequencies will enhance spatial specificity and enable simultaneous eliciting and monitoring brain activities. Moreover, the use of non-periodic pulse sequences may reduce unintended stimulations on auditory cortex, which might be caused by transmitting periodic bursting patterns. A platform for ultrasound brain stimulations for small animal models, including a soft housing 10 MHz needle transducer with a beam size of 680 µm, random transmission sequences, and optical imaging systems, was developed. The platform can deliver focal stimulations to the visual and barrel cortex of mice and monitor subsequent brain activities. The stimulated sites in both the visual and primary somatosensory cortices (S1) showed approximately two to three times higher neuronal calcium signal levels than those in peripheral regions. Activities in the auditory cortex were elicited by periodic sequence stimulation, while it was reduced by 67 and 35% for barrel and visual cortex stimulation with the random sequence, respectively.

Acquisition System Based on Multisensors for Preserving Traditional Korean Painting.

Rapid industrialization has significantly influenced people's lifestyles in the recent decades, and the influence of traditional culture is diminishing. Recently, several studies attempted to simultaneously utilize various sensors to record delicate and sophisticated performances of intangible cultural heritage (ICH). Although painting is one of the most common ICH of human history, few research studies have recorded traditional painting work. In this paper, we aim to lay the groundwork for reviving Korean painting, even if there would be no painters to produce these traditional Korean paintings in the future. We propose a novel multisensor-based acquisition system that records traditional Korean painting work while minimizing interference in the work. The proposed system captures real-time data originating from the painter, brushes, pigments, and canvas, which are the essential components of the painting work. We utilized the proposed system to capture the painting work by two experts, and we visualize the captured data. We showed the various results of statistical analysis, and also discussed the usability.

Bee venom ameliorates ovalbumin induced allergic asthma via modulating CD4+CD25+ regulatory T cells in mice.

Asthma is a potentially life-threatening inflammatory disease of the lung characterized by the presence of large numbers of CD4+ T cells. These cells produce the Th2 and Th17 cytokines that are thought to orchestrate the inflammation associated with asthma. Bee venom (BV) has traditionally been used to relieve pain and to treat chronic inflammatory diseases. Recent reports have suggested that BV might be an effective treatment for allergic diseases. However, there are still unanswered questions related to the efficacy of BV therapy in treating asthma and its therapeutic mechanism. In this study, we evaluated whether BV could inhibit asthma and whether BV inhibition of asthma could be correlated with regulatory T cells (Treg) activity. We found that BV treatment increased Treg populations and suppressed the production of Th1, Th2 and Th17-related cytokines in an in vitro culture system, including IL2, IL4, and IL17. Interestingly, production of IL10, an anti-inflammatory cytokine secreted by Tregs, was significantly augmented by BV treatment. We next evaluated the effects of BV treatment on allergic asthma in an ovalbumin (OVA)-induced mouse model of allergic asthma. Cellular profiling of the bronchoalveolar lavage (BAL) and histopathologic analysis demonstrated that peribronchial and perivascular inflammatory cell infiltrates were significantly lowered following BV treatment. BV also ameliorated airway hyperresponsiveness, a hallmark symptom of asthma. In addition, IL4 and IL13 levels in the BAL fluid were decreased in the BV treated group. Surprisingly, the beneficial effects of BV treatment on asthma were eradicated following Treg depletion by anti-CD25 antibody injection, suggesting that the major therapeutic targets of BV were Tregs. These results indicate that BV efficiently diminishes bronchial inflammation in an OVA-induced allergic asthma murine model, and that this effect might correlate with Tregs, which play an important role in maintaining immune homeostasis and suppressing the function of other T cells to limit the immune response. These results also suggest that BV has potential therapeutic value for controlling allergic asthma responses.

Upregulation of interferon-gamma and interleukin-4, Th cell-derived cytokines by So-Shi-Ho-Tang (Sho-Saiko-To) occurs at the level of antigen presenting cells, but not CD4 T cells.

ETHNOPHARMACOLOGICAL RELEVANCE: So-Shi-Ho-Tang (SSHT) or known as Sho-Saiko-To in Japanese and Xiao-Chai-Hu-Tang in Chinese has been used to treat chronic liver disease and other infections, and its hepatoprotective effects have been widely studied. AIM OF THE STUDY: We tried to investigate the immunomodulatory effect of SSHT on interferon (IFN)-gamma and interleukin (IL)-4 and their Th1/Th2 transcription factors in vivo and in vitro since these two cytokines are important in determining the type of cell-mediated inflammatory and humoral responses. MATERIALS AND METHODS: SSHT was orally given to BALB/c mice for 7 days and then injected with anti-CD3 mAb intravenously. IFN-gamma, IL-4, IL-2 and Th1/Th2-specific transcription factors as well as splenocyte subsets were measured. Splenocytes and CD4 T cells were cultured with anti-CD3 or anti-CD3/anti-CD28 in the presence of SSHT, its constituent herbs and baicalin, and the levels of cytokines and transcription factors were measured by ELISA and western blotting. RESULTS: Oral administration of SSHT to mice in response to i.v. anti-CD3 injection enhanced the expression of IFN-gamma, IL-4 and IL-2 in the serum and spleen at the secreted protein and mRNA level. This was accompanied by the upregulation of CD69 and CD4 T cell populations by flow cytometry. The upregulation of IFN-gamma and IL-4 by SSHT did not occur in anti-CD3/anti-CD28 stimulated CD4 T cells in vitro. However, SSHT was capable of producing the cytokines in anti-CD3 stimulated splenocytes even in the absence of CD28, suggesting a role for some soluble factors produced by antigen presenting cells (APC). In support of this, we found that SSHT increased IL-12 and IL-6 in the same cells. STAT4, but not T-bet, was involved in the upregulation of IFN-gamma by SSHT while the increased IL-4 expression was accompanied by a parallel increase in c-Maf but independent of STAT6 and GATA-3. CONCLUSION: These data indicate that the upregulation of IFN-gamma and IL-4 by SSHT must occur through some interactions between APC and CD4 T cells. Taken together, the present data provide additional information on some of the immunological mechanisms of SSHT for treatment of liver diseases and infections.

Differential regulation of the antiapoptotic action of B-cell lymphoma 2 (Bcl-2) and B-cell lymphoma extra long (Bcl-xL) by c-Jun N-terminal protein kinase (JNK) 1-involved pathway in neuroglioma cells.

Here, we confirmed that stable expression of B-cell lymphoma-xL (Bcl-xL) in N18TG neuroglioma cells could suppress c-Jun N-terminal protein kinase (JNK) activation, nuclear fragmentation, and cell death caused by etoposide treatment. Moreover, additional overexpression of JNK1 led to partially antagonize the antiapoptotic environment attained by Bcl-xL, implying that JNK1-involved pathway may play a role in down-regulation of the antiapoptotic effect of Bcl-xL. However, the antagonistic effect of JNK1 on the antiapoptotic action of Bcl-xL was significantly weaker than that on the action of Bcl-2. Interestingly, we found that overexpression of JNK1 led to increase of Bcl-xL expression. Thus, these results suggest that Bcl-xL and Bcl-2 may induce its antiapoptotic effect in a different mechanism, provoking the possibility of involvement of JNK1-involved pathway in Bcl-xL expression.