Ultrasound Neuromodulation Reduces Demyelination in a Rat Model of Multiple Sclerosis

Abstract

Microglia, astrocytes, and oligodendrocyte progenitor cells (OPCs) may serve as targets for remyelination-enhancing therapy. Low-intensity pulsed ultrasound (LIPUS) has been demonstrated to ameliorate myelin loss and inhibit neuroinflammation in animal models of brain disorders; however, the underlying mechanisms through which LIPUS stimulates remyelination and glial activation are not well-understood. This study explored the impacts of LIPUS on remyelination and resident cells following lysolecithin (LPC)-induced local demyelination in the hippocampus. Demyelination was induced by the micro-injection of 1.5 μL of 1% LPC into the rat hippocampus, and the treatment groups received daily LIPUS stimulation for 5 days. The therapeutic effects of LIPUS on LPC-induced demyelination were assessed through immunohistochemistry staining. The staining was performed to evaluate remyelination and Iba-1 staining as a microglia marker. Our data revealed that LIPUS significantly increased myelin basic protein (MBP) expression. Moreover, the IHC results showed that LIPUS significantly inhibited glial cell activation, enhanced mature oligodendrocyte density, and promoted brain-derived neurotrophic factor (BDNF) expression at the lesion site. In addition, a heterologous population of microglia with various morphologies can be found in the demyelination lesion after LIPUS treatment. These data show that LIPUS stimulation may serve as a potential treatment for accelerating remyelination through the attenuation of glial activation and the enhancement of mature oligodendrocyte density and BDNF production.

Knowledge mapping and global trends in the field of low-intensity pulsed ultrasound and endocrine and metabolic diseases: a bibliometric and visual analysis from 2012 to 2022

“…Feng-Yi Yang has the highest total citation frequency and primarily focuses on combining LIPUS to treat neurological disorders. He proved that LIPUS stimulation can be a potential therapeutic method by accelerating myelin regeneration through weakening glial cell activation, enhancing mature oligodendrocyte density, and increasing the production of BDNF ( 25 ). Abdominal LIPUS stimulation can combat neuroinflammation by enhancing tight junction protein levels and inhibiting colonic inflammation ( 26 ).…”

Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation

“…LIPUS not only has the potential to improve tissue-microelectrode bio-integration for BCIs, but also provide a new opportunity for treating other dysfunctions in biological processes 131,132 , CNS injuries 133 and neurodegenerative diseases [134][135][136] . For example, in response to ischemic injury, microglia migrate toward the injury site to phagocytose cell debris and protect damaged cells, reducing the inflammation caused by dead cell corpses 137 .…”

Neuronal activity and remyelination: new insights into the molecular mechanisms and therapeutic advancements

“…Ultrasound treatment was demonstrated to enhance remyelination in the LPC-induced demyelination model of MS by alleviating neuroinflammation, enhancing mature oligodendrocyte density, and promoting BDNF expression ( Yang et al, 2022 ). TUS has higher spatial resolution and deeper penetration, which can induce short-term and long-term changes in neuronal excitability and spontaneous firing rates.…”