The modulation of the blood–brain barrier by focused ultrasound stimulates oligodendrogenesis
5 affiliations
- 1Biological Sciences, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, ON Canada
- 2Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON Canada
- 3Physical Sciences, Sunnybrook Research Institute, Toronto, ON Canada
- 4Department of Biochemistry, University of Toronto, Toronto, ON Canada
- 5Department of Medical Biophysics, Temerty Faculty of Medicine, University of Toronto, Toronto, ON Canada
Abstract
Focused ultrasound (FUS) combined with intravenous microbubbles (MB) enables precise and reversible modulation of the blood–brain barrier (BBB) to enhance the delivery of therapeutics from the blood to targeted brain areas. Beyond this application, we discovered over a decade ago that FUS-BBB modulation, without the addition of exogenous therapeutics, activates endogenous regenerative events, including hippocampal neurogenesis. Here, we investigate the effects of FUS on oligodendrogenesis, a key process for myelination and white matter integrity. In adult mice, we targeted FUS-BBB modulation unilaterally to the hippocampus. The proliferation of oligodendrocyte progenitor cells (OPCs) was quantified at 1, 4, 7, and 10 days post-treatment and myelinating oligodendrocytes were assessed at 30 days. At 1 and 4 days post-sonication, the proliferation of hippocampal OPCs increased by 6.8-fold and 2.3-fold, respectively; this resulted in a 5.3-fold increase in myelinating oligodendrocytes one month later. Next, we tested the robustness of FUS-induced oligodendrogenesis using an independent experimental design and targeting the striatum in a separate cohort of mice. The proliferation of striatal OPCs increased by 3.9-fold at 7 days post-FUS. This led to a 5.2-fold increase in oligodendrogenesis 30 days post-treatment, as observed in the hippocampus. Finally, we found that treatments at the same FUS parameters but without MB and without altering the BBB, did not lead to the proliferation of OPCs or oligodendrogenesis. Therefore, with these FUS parameters, MB-induced BBB modulation emerged as a key factor that promoted oligodendrogenesis. Given the long-validated application of FUS-BBB modulation for drug delivery, the additional stimulation of oligodendrogenesis broadens the therapeutic potential of this modality for white matter repair.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s40478-026-02364-1.
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BibTeX
@article{noseworthy2026modulation,
title = {{The modulation of the blood–brain barrier by focused ultrasound stimulates oligodendrogenesis}},
author = {Kate Noseworthy and Joseph Silburt and Alessia Apa and Luis Fernando Rubio-Atonal and Sheng-Kai Wu and Carol Schuurmans and Kullervo Hynynen and Isabelle Aubert},
journal = {Acta Neuropathologica Communications},
year = {2026},
month = jul,
doi = {10.1186/s40478-026-02364-1},
url = {https://doi.org/10.1186/s40478-026-02364-1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - The modulation of the blood–brain barrier by focused ultrasound stimulates oligodendrogenesis
AU - Kate Noseworthy
AU - Joseph Silburt
AU - Alessia Apa
AU - Luis Fernando Rubio-Atonal
AU - Sheng-Kai Wu
AU - Carol Schuurmans
AU - Kullervo Hynynen
AU - Isabelle Aubert
PY - 2026
DA - 2026/07/11
JO - Acta Neuropathologica Communications
DO - 10.1186/s40478-026-02364-1
UR - https://doi.org/10.1186/s40478-026-02364-1
AB - Focused ultrasound (FUS) combined with intravenous microbubbles (MB) enables precise and reversible modulation of the blood–brain barrier (BBB) to enhance the delivery of therapeutics from the blood to targeted brain areas. Beyond this application, we discovered over a decade ago that FUS-BBB modulation, without the addition of exogenous therapeutics, activates endogenous regenerative events, including hippocampal neurogenesis. Here, we investigate the effects of FUS on oligodendrogenesis, a key process for myelination and white matter integrity. In adult mice, we targeted FUS-BBB modulation unilaterally to the hippocampus. The proliferation of oligodendrocyte progenitor cells (OPCs) was quantified at 1, 4, 7, and 10 days post-treatment and myelinating oligodendrocytes were assessed at 30 days. At 1 and 4 days post-sonication, the proliferation of hippocampal OPCs increased by 6.8-fold and 2.3-fold, respectively; this resulted in a 5.3-fold increase in myelinating oligodendrocytes one month later. Next, we tested the robustness of FUS-induced oligodendrogenesis using an independent experimental design and targeting the striatum in a separate cohort of mice. The proliferation of striatal OPCs increased by 3.9-fold at 7 days post-FUS. This led to a 5.2-fold increase in oligodendrogenesis 30 days post-treatment, as observed in the hippocampus. Finally, we found that treatments at the same FUS parameters but without MB and without altering the BBB, did not lead to the proliferation of OPCs or oligodendrogenesis. Therefore, with these FUS parameters, MB-induced BBB modulation emerged as a key factor that promoted oligodendrogenesis. Given the long-validated application of FUS-BBB modulation for drug delivery, the additional stimulation of oligodendrogenesis broadens the therapeutic potential of this modality for white matter repair. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s40478-026-02364-1.
SN - 2051-5960
ER -