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Low-Intensity Pulsed Ultrasound Effects on the Human Blood Brain Barrier

ABSTRACT: Low-Intensity Pulsed Ultrasound Effects on the Human Blood Brain Barrier

PROVIDER: PRJNA858102 | ENA |

REPOSITORIES: ENA

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Low-Intensity Pulsed Ultrasound Effects on the Human Blood Brain Barrier

Project description:Analysis of human peritumoral brain following a low-intensity pulsed ultrasound (LIPU) mediated opening of the blood brain barrier, to enhance the delivery of systemic chemotherapies (paclitaxel or carboplatin).

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Identification of early response genes to low-intensity pulsed ultrasound in bone marrow stromal cells

Project description:Low-intensity pulsed ultrasound (LIPUS) has been applied as a therapeutic adjunct to promote fracture healing. However, the detailed molecular mechanisms by which LIPUS promotes bone fracture healing have not yet been fully elucidated. In the present study, the early response genes elicited by low-intensity pulsed ultrasound (LIPUS) in bone marrow stromal cells (BMSCs) were investigated using GeneChip® oligonucleotide microarrays.

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Low-intensity pulsed ultrasound-mediated blood-brain barrier opening increases anti programmed death-ligand 1 delivery and efficacy in Gl261 mouse model

Project description:Therapeutic antibodies targeting immune checkpoints have shown limited efficacy in clinical trials in glioblastoma (GBM) patients. Ultrasound-mediated blood-brain barrier opening (UMBO) using low-intensity pulsed ultrasound improved drug delivery to the brain. We explored the safety and the efficacy of UMBO plus immune checkpoint inhibitors in preclinical models of GBM. A Blood-brain barrier (BBB) opening was performed using a 1 MHz preclinical ultrasound system in combination with 10µl/g microbubbles. Brain penetration of immune checkpoint inhibitors was determined, and immune cell populations were evaluated using flow cytometry.The impact of repeated treatments on survival was determined. In syngeneic GL261-bearing immunocompetent mice, we showed that UMBO safely and repeatedly open the BBB. BBB opening was confirmed visually and microscopically using Evans’s blue dye and magnetic resonance imaging. UMBO plus anti-PDL-1 was associated with a significant improvement of the overall survival compared to anti-PD-L1 alone. Using mass spectroscopy, we showed that the penetration of therapeutic antibodies can be increased when delivered intravenously compared to non-sonicated brains. Furthermore, we observed an enhancement of activated microglia percentage when combined with anti-PD-L1. Here, we report that the combination of UMBO and anti-PD-L1 dramatically increases GL261-bearing mice's survival compared to their counterparts treated with anti-PD-L1 alone. Our study highlights the BBB as a limitation to overcome to increase the efficacy of anti-PD-L1 in GBM and supports clinical trials combining UMBO and in GBM patients.

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Anti-inflammatory role of low intensity pulsed ultrasound in inhibiting LPS-induced M1 polarization of RAW264.7 via Wnt2b/AXIN/β-catenin

Project description:Low-intensity pulsed ultrasound (LIPUS) is a special type of low intensity ultrasound. In periodontal disease, LIPUS was applied as an adjuvant and non-invasive therapeutic treatment. While, the specific mechanism of LIPUS in the treatment of periodontal disease is not quite clear.RAW264.7 cells were induced to M1/M2 macrophage-like polarization by LPS/IL4. LIPUS was performed to stimulate RAW264.7 cells at an intensity of 45 mW/cm2, 25 min, interval 24 h, twice. The polyA mRNA sequencing of LPS induced RAW264.7 cells, LPS induced and LIPUS treated RAW264.7 cells were conducted.Our results suggested that LIPUS played an anti-inflammatory role by inhibiting LPS-induced M1 polarization of RAW264.7 cells in an Wnt2b/AXIN/β-catenin dependent way. LIPUS may inhibit inflammation in periodontal diseases by regulating macrophage differentiation, so as to play a therapeutic role in periodontal diseases.

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Osteocytes as main responders to Low Intensity Pulsed Ultrasound for the treatment of fracture healing

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Gene expression in response to low-intensity pulsed ultrasound treatment of bone marrow cells under osteogenic conditions in vitro

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Gene expression in response to low-intensity pulsed ultrasound treatment of bone marrow cells under osteogenic conditions in vitro

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