Abstract:<b><i>Introduction:</i></b> The low-intensity pulsed ultrasound (LIPUS) is one of the popular treatment modalities allowing to boost the proliferation, differentiation, and migratory activity of cells, which might be a powerful strategy for anti-aging. Seeking a novel setup for LIPUS would benefit the development of ultrasound therapeutics. <b><i>Methods:</i></b> Here, we proposed a novel underwater exposure setup of LIPUS. C57BL/6 mice were reared in the designa… Show more
“…3). Together with recent literature demonstrating that LIPUS can reduce senescent marker (P16 INK4a ) in aged mouse 131 , LIPUS treatment appears to have potential anti-aging effects on microglia.…”
Section: Discussionsupporting
confidence: 60%
“…LIPUS not only has the potential to improve tissue-microelectrode bio-integration for BCIs, but also provide a new opportunity for treating other dysfunctions in biological processes 131,132 , CNS injuries 133 and neurodegenerative diseases [134][135][136] . For example, in response to ischemic injury, microglia migrate toward the injury site to phagocytose cell debris and protect damaged cells, reducing the inflammation caused by dead cell corpses 137 .…”
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 µm2/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.
“…3). Together with recent literature demonstrating that LIPUS can reduce senescent marker (P16 INK4a ) in aged mouse 131 , LIPUS treatment appears to have potential anti-aging effects on microglia.…”
Section: Discussionsupporting
confidence: 60%
“…LIPUS not only has the potential to improve tissue-microelectrode bio-integration for BCIs, but also provide a new opportunity for treating other dysfunctions in biological processes 131,132 , CNS injuries 133 and neurodegenerative diseases [134][135][136] . For example, in response to ischemic injury, microglia migrate toward the injury site to phagocytose cell debris and protect damaged cells, reducing the inflammation caused by dead cell corpses 137 .…”
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 µm2/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.
“…IL-7 is intrinsically involved in T cell homeostasis as an essential cytokine that enhances the persistence of T cells in vivo [ 21 ]. Our previous study [ 22 ] found that IL-2 and IL-7 levels in the spleen were still elevated in middle-aged (12–14 months old) C57BL/6 mice after LIPUS underwater irradiation and after one month of follow-up. The present study additionally demonstrates the significant impact of LIPUS on the release of upgraded IL-2 and IL-7.…”
Tumor immunotherapy is booming around the world. However, strategies to activate the immune system and alleviate the immunosuppression still need to be refined. Here, we demonstrate for the first time that low-intensity pulsed ultrasound (LIPUS, spatial average time average intensity (Isata) is 200 mW/cm2, frequency is 0.3 MHz, repetition frequency is 1 kHz, and duty cycle is 20%) triggers the immune system and further reverses the immunosuppressive state in the mouse models of breast cancer by irradiating the spleen of mice. LIPUS inhibited tumor growth and extended survival in mice with 4 T-1 tumors. Further studies had previously shown that LIPUS enhanced the activation of CD4+ and CD8+ T cells in the spleen and led to significant changes in cytokines, as well as induced upregulation of mRNA levels involved in multiple immune regulatory pathways in the spleen. In addition, LIPUS promoted tumor-infiltrating lymphocyte accumulation and CD8+ T cell activation and improved the dynamics of cytokines/chemokines in the tumor microenvironment, resulting in a reversal of the immunosuppressive state of the tumor microenvironment. These results suggest a novel approach to activate the immune response by irradiating the spleen with LIPUS.
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