| Summary: | Despite current therapies for peripheral nerve injuries (PNIs), only approximately half of 20 million of patients receiving treatment each year regain satisfactory motor and sensory functionality (Grinsell & Keating, 2014). Both the prevalence and poor prognosis for PNI patients underscore a need for novel treatment options. While electrical stimulation has shown promise for nerve regeneration, it often requires invasive surgery to implant electrodes and can result in
scar tissue and introduce infection. Ultrasound stimulation (US) can achieve similar regenerative effects as electrical stimulation but can be delivered completely non-invasively and at sub-millimeter resolution. In fact, US has been shown to facilitate action potential firing and synaptic vesicle release in neurons. To implement US safely as a potential therapy for PNI, the effect of US on neuronal cytoskeletal rearrangement and its effect on proximal glial cells such as Schwann cells
(SCs) needs to be investigated further. Therefore, this dissertation aims to expand upon previous studies of US on neurons alone, by observing the impact of US on neuron/SC cocultures and on the SCs alone. In the studies described herein, it was determined that US can enhance neurite outgrowth and branching in DRG neurons in an acoustic intensity-dependent manner in both DRG neuron cultures alone and in DRG/SC cocultures. Mean longest neurite formation was unaffected by US after 24
hours of analysis, but the hourly rate of total neurite outgrowth increased by more than double during the first hour after stimulation. Furthermore, neuronal response to US using the parameters described herein did not alter neurite and branching in a calcium-dependent manner based. Lastly, conditioned media from SC subjected to US exhibited significant changes in morphology in neurons supplied with the conditioned media versus controls, highlighting a contact-independent,
secreted-factor mediated interaction between DRGs and SCs. Overall, this dissertation provides a foundation for investigating the mechanisms by which neurons and glia respond to US. An understanding of these mechanisms is crucial for safe and effective implementation of US for clinical use for treatment of PNI for optimizing acoustic parameters for intended therapeutic outcomes.
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