Objective
It is unknown whether ultrasound-induced blood–brain barrier (BBB) disruption can
promote epileptogenesis and how BBB integrity changes over time after sonication.
Methods
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.
Results
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.
Conclusion
Our experiments in mice provide persuasive evidence of the safety of LIPU-induced
BBB opening as a therapeutic modality for neurological diseases.
Keywords
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Article info
Publication history
Published online: March 04, 2023
Accepted:
February 1,
2023
Received in revised form:
January 26,
2023
Received:
May 23,
2022
Identification
Copyright
© 2023 World Federation for Ultrasound in Medicine & Biology. All rights reserved.
