The effects of low intensity focused ultrasonic stimulation on dorsal root ganglion neurons and Schwann cells in vitro.

Satisfactory treatment of peripheral nerve injury (PNI) faces difficulties owing to the intrinsic biological barriers in larger injuries and invasive surgical interventions. Injury gaps >3 cm have low chances of full motor and sensory recovery, and the unmet need for PNI repair techniques which increase the likelihood of functional recovery while limiting invasiveness motivate this work. Building upon prior work in ultrasound stimulation (US) of dorsal root ganglion (DRG) neurons, the effects of US on DRG neuron and Schwann cell (SC) cocultures were investigated to uncover the role of SCs in mediating the neuronal response to US in vitro. Acoustic intensity-dependent alteration in selected neuromorphometrics of DRG neurons in coculture with SCs was observed in total outgrowth, primary neurites, and length compared to previously reported DRG monoculture in a calcium-independent manner. SC viability and proliferation were not impacted by US. Conditioned medium studies suggest secreted factors from SCs subjected to US impact DRG neuron morphology. These findings advance the current understanding of mechanisms by which these cell types respond to US, which may lead to new noninvasive US therapies for treating PNI.

The Body Acoustic: Ultrasonic Neuromodulation for Translational Medicine.

For the greater part of the last century, ultrasound (US) has seen widespread use in applications ranging from materials science to medicine. The history of US in medicine has also seen promising success in clinical diagnostics and regenerative medicine. Recent studies have shown that US is able to manipulate the nervous system, leading toward potential treatment for various neuropathological conditions, a phenomenon known as ultrasonic neuromodulation (NM). Ultrasonic NM is a promising alternative to pharmaceuticals and surgery, due to high spatiotemporal resolution combined with the potentially noninvasive means of application. Current advances have made progress in establishing effective dosage limits, waveform parameters, and stimulus regimes in order to achieve desired effects in a variety of tissue and cell types. However, to date there has been limited systematic analysis of the complex variables involved in creating a therapeutic US stimulation regime specifically tailored to the nervous system. Without a fundamental understanding of the effects of US on neural tissue, including the surrounding bone, musculature, and vasculature, the safety and efficacy of US as an NM tool is yet to be determined. Advances in imaging technology and focusing hardware highlight new avenues for potential clinical applications for therapeutic ultrasonic stimulation. US may be an alternative to electrical and magnetic means of NM for targets in the central nervous system as well as in the peripheral and autonomic nervous systems. This review provides a historical perspective on the past, present, and future of US as a translational therapeutic.