Original Contribution| Volume 49, ISSUE 5, P1327-1336, May 2023

Safety Profile of Low-Intensity Pulsed Ultrasound–Induced Blood–Brain Barrier Opening in Non-epileptic Mice and in a Mouse Model of Mesial Temporal Lobe Epilepsy

  • Bertrand Mathon
    Corresponding author. Department of Neurosurgery, La Pitié–Salpêtrière University Hospital, 47–83, boulevard de l'Hôpital, 75651 Paris Cedex 13, France
    Department of Neurosurgery, Sorbonne University, APHP, La Pitié-Salpêtrière Hospital, Paris, France

    Paris Brain Institute, ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne University, Paris, France

    Sorbonne University, GRC 23, Brain Machine Interface, APHP, La Pitié-Salpêtrière Hospital, Paris, France

    Advanced Surgical Research Technology Lab, Sorbonne University, Paris, France
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  • Vincent Navarro
    Paris Brain Institute, ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne University, Paris, France

    Epileptology Unit, Department of Neurology, Sorbonne University, APHP, La Pitié-Salpêtrière Hospital, Paris, France
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  • Sarah Lecas
    Paris Brain Institute, ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne University, Paris, France
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  • Delphine Roussel
    Paris Brain Institute, ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne University, Paris, France
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  • Stéphane Charpier
    Paris Brain Institute, ICM, INSERM U 1127, CNRS UMR 7225, Sorbonne University, Paris, France
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  • Alexandre Carpentier
    Department of Neurosurgery, Sorbonne University, APHP, La Pitié-Salpêtrière Hospital, Paris, France

    Sorbonne University, GRC 23, Brain Machine Interface, APHP, La Pitié-Salpêtrière Hospital, Paris, France

    Advanced Surgical Research Technology Lab, Sorbonne University, Paris, France
    Search for articles by this author


      It is unknown whether ultrasound-induced blood–brain barrier (BBB) disruption can promote epileptogenesis and how BBB integrity changes over time after sonication.


      To gain more insight into the safety profile of ultrasound (US)-induced BBB opening, we determined BBB permeability as well as histological modifications in C57BL/6 adult control mice and in the kainate (KA) model for mesial temporal lobe epilepsy in mice after sonication with low-intensity pulsed ultrasound (LIPU). Microglial and astroglial changes in ipsilateral hippocampus were examined at different time points following BBB disruption by respectively analyzing Iba1 and glial fibrillary acidic protein immunoreactivity. Using intracerebral EEG recordings, we further studied the possible electrophysiological repercussions of a repeated disrupted BBB for seizure generation in nine non-epileptic mice.


      LIPU-induced BBB opening led to transient albumin extravasation and reversible mild astrogliosis, but not to microglial activation in the hippocampus of non-epileptic mice. In KA mice, the transient albumin extravasation into the hippocampus mediated by LIPU-induced BBB opening did not aggravate inflammatory processes and histologic changes that characterize the hippocampal sclerosis. Three LIPU-induced BBB opening did not induce epileptogenicity in non-epileptic mice implanted with depth EEG electrodes.


      Our experiments in mice provide persuasive evidence of the safety of LIPU-induced BBB opening as a therapeutic modality for neurological diseases.


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