Low-intensity pulsed ultrasound delays disease progression of amyotrophic lateral sclerosis by the motor cortex neuromodulation

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord, and there are no effective drug treatments. Low-intensity pulsed ultrasound (LIPUS) has garnered attention as a promising noninvasive neuromodulation method. In this study, we investigated its effects on the motor cortex and underlying mechanisms using the SODG93A mouse model of ALS. Our results showed that LIPUS treatment delayed disease onset and prolonged lifespan in ALS mice. LIPUS significantly increased cerebral blood flow in the motor cortex by preserving cerebral vascular integrity and increasing microvascular density, as evidenced by imaging and histological analyses. RNA sequencing analysis revealed that LIPUS substantially reduced the expression of genes associated with neuroinflammation. These findings suggest that LIPUS applied to the motor cortex may represent a potentially effective therapeutic tool, either alone or in combination with drug therapy, for the treatment of ALS.