Researchers at Sunnybrook Research Institute and the University of Toronto, led by Isabelle Aubert, PhD, recently published results of a preclinical study that examine focused ultrasound’s potential to stimulate the production of oligodendrocytes, the cells responsible for making myelin, which plays an important role in neuronal function.
The study, “The modulation of the blood-brain barrier by focused ultrasound stimulates oligodendrogenesis,” examined a potential regenerative effect of focused ultrasound–mediated blood-brain barrier (BBB) modulation. The researchers found that the treatment increased the production of new oligodendrocytes in two regions of the mouse brain.
What is Myelin?
Myelin is an insulating layer that surrounds many nerve fibers. It helps electrical signals travel efficiently through the brain. Bundles of nerve fibers, many of which are covered in myelin, make up much of the brain’s white matter, which forms communication pathways that connect different brain regions. In the brain, oligodendrocytes are the cells responsible for producing myelin.
Changes in myelin, the white matter of the brain, and oligodendrocytes are increasingly being recognized as part of Alzheimer’s disease biology because of their impact on the cell-to-cell communication involved in learning and memory.
These findings have prompted researchers to investigate whether promoting myelin maintenance and repair could serve as a complementary therapeutic approach alongside treatments targeting amyloid, tau, and other neuronal disease processes.
Testing Focused Ultrasound in Mice
The researchers used magnetic resonance imaging–guided focused ultrasound plus intravenous microbubbles to temporarily alter the BBB on one side of the brain, targeting the hippocampus or striatum in healthy mice.
The team then tracked oligodendrocyte precursor cells (OPCs) to see whether they multiplied and developed into myelin-producing oligodendrocytes. They examined the brains at several time points after treatment and compared treated areas with untreated areas. They also tested focused ultrasound without microbubbles to determine whether they were necessary for the response at these parameters.
What the Researchers Found
Focused ultrasound–mediated BBB modulation increased the number of dividing OPCs in both brain regions. By 30 days, newly generated myelinating oligodendrocytes were about five times more abundant in treated areas than in untreated areas.
The treatment also caused a temporary response from other brain cells that may have contributed to the effect. When focused ultrasound was applied without microbubbles, the researchers did not see the same increase in oligodendrocyte production, suggesting that BBB modulation in presence of microbubbles played an important role.
The researchers observed no signs of brain damage within or around the treatment zone, including absence of edema, hemorrhage, vascular injury, or neuronal damage.
Why This Research Matters
Focused ultrasound–mediated BBB disruption is widely being studied to deliver therapeutics to the brain. These findings suggest that the approach may also stimulate the brain’s own cells involved in producing myelin, without delivering a drug.
This discovery could be valuable to the Alzheimer’s disease community. If focused ultrasound could stimulate the production and maturation of oligodendrocytes in an Alzheimer’s disease model, it may eventually help support the brain’s communication networks. It could also complement focused ultrasound strategies designed to deliver therapeutics or influence Alzheimer’s disease pathology.
However, the results remain preclinical. The study was performed in healthy, young, male mice, and the researchers did not directly measure new myelin formation around axons, changes in white matter structure, memory, or disease progression. The study also did not establish that increased oligodendrocyte production leads to functional remyelination.
Future studies will need to determine whether the response occurs in aged animals and disease models, whether it can be reproduced in both sexes, how long it lasts, and whether it improves brain function. Researchers will also need to clarify which aspects of the treatment, including BBB modulation, microbubbles, and ultrasound parameters, drive the response.
This research was supported in part by the Focused Ultrasound Foundation and BrightFocus Foundation partnership, with additional support from the Canadian Institutes of Health Research, Canada Research Chairs Program, Temerty Chair in Focused Ultrasound Research, National Institutes of Health, and other organizations.
See the open-access study in Acta Neuropathologica Communications.