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Ultrasound Induced Blood-brain Barrier Opening on Rodents : from Nanoparticles Delivery to a Therapy for Alzheimer’s Disease

Abstract : The blood-brain barrier (BBB) plays a crucial role in maintaining the hemostasis of the brain and protects it from pathogens. The BBB prevents molecules with a molecular weight higher than 400 Da to enter the brain. Crucial, the BBB becomes a limit to deliver drugs to the brain. Low intensity focused ultrasound and microbubbles are a unique tool to open the BBB, in a safe and reversible way, to deliver drugs to the brain. The first part of the PhD was dedicated to developing new strategies for BBB opening. To do so, I measured the attenuation of the ultrasound beam by the skull and studied the dependency of the intensity and of the duration of the BBB opening on the acoustic parameters. Thanks to these developments, I was able to deliver many kinds of nanoparticles to rodent brains and I could observe their delivery with techniques such as magnetic resonance imaging (MRI), positron emission tomography, phase-contrast X-ray imaging, mass spectroscopy or histology. The second part of my PhD was focused on applying this technology to Alzheimer’s disease (AD). I optimized a T2* MRI protocol at very high resolution for ex vivo imaging of amyloid plaques in the cortex of mice modeling AD. I developed a semi-automatic image treatment to detect and quantify the amyloid load. Finally, I tested a repeated BBB opening as a therapy for AD and showed that repeated BBB openings could have a beneficial impact on the memory on rodents modeling AD.
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Matthieu Gerstenmayer. Ultrasound Induced Blood-brain Barrier Opening on Rodents : from Nanoparticles Delivery to a Therapy for Alzheimer’s Disease. Biological Physics [physics.bio-ph]. Université Paris Saclay (COmUE), 2018. English. ⟨NNT : 2018SACLS424⟩. ⟨tel-02015610⟩

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