The research objective of this proposal is to develop a method to detect whether regenerating neurons are communicating appropriately before they regrow to their target tissues. Currently, successful regeneration of nerves in vivo is evaluated by nerve conduction velocity and muscle contraction. The major drawback to currently available methods is that either complete reconnectivity or final reinnervation of target tissues must occur for testing to be possible. The proposed technique will utilize a multi-disciplinary approach to detect synaptic signals as a measure of proper nerve growth in the initial stages of regeneration, rather than waiting until the nerve has reconnected and innervated target tissues.
The aims to accomplish this objective are (i) to characterize synaptic signals from neurons regrowing on a 2 dimensional surface, or within a 3 dimensional scaffold, and detected with an x-y multi-channel interdigitated array detector, and (ii) to design a 3 dimensional (x-y-z) interdigitated array detector to measure synaptic signals from regrowing neurons within clinically relevant 3D scaffold materials. The long-term outcome of this project has the potential to meet the global need for a practical and inexpensive method to rapidly assess the efficacy of nerve regeneration.
Medical advances in tissue engineering require an improved ability to rapidly evaluate nerve regeneration. This proposal will develop a method to assay signaling of nerves in the early stages of regeneration, an ability that basic and essential research for medical advancements currently lacks. Specifically, this project will allow a first step towards the ability to make early distinctions between failure of a nerve to regenerate, and failure of the target to appropriately receive innervation.
|Adams, Robert D; Willits, Rebecca K; Harkins, Amy B (2016) Computational modeling of neurons: intensity-duration relationship of extracellular electrical stimulation for changes in intracellular calcium. J Neurophysiol 115:602-16|