Synthetic Nerve Endings for Restoring the Axo-Axonal Transport
Authors: Abdullayeva Nazrin , Seckin Deniz Naz , Sankir Mehmet , Demirci Sankir Nurdan , Seckin Hakan 
Published: February 2020

Currently, more than 450 million people are globally suffering from some type of neurological diseases that can hardly be treated [1].These diseases are caused by distorted electrical and neurochemical signaling in the nervous system. The awareness of this worldwide problem is not brought in yet and definitive treatment has not been introduced so far [2]. Most of therapies associated with neurological disorders are based on medical treatment such as medical therapy or electric stimulation [3]. However, results are temporary and ineffective. The major effect obtained so far, was to conceal the disease and this was just not enough.

In our study, by taking into consideration this problem we are presenting a biomimetic system that duplicates the function of a neural cell and helps to reinstitute the defective electrochemical transport of nervous system. Nerve impulses are communicated across synapses by diffusible molecules called neurotransmitters, of which one is acetylcholine [3,4]. Acetylcholine molecules are contained in the axon foot inside vesicles. After the release of acetylcholine into the synaptic cleft, it binds to the cholinergic receptors located on the postsynaptic neuron and mediate excitation or inhibition on postsynaptic cells and thus causing the transportation of neural signal. Our system of artificial neuron synthesized from conductive, biocompatible polymeric membrane (disulfonated poly arylene ether sulfone) [5], inserted into a micro scaled cylindrical tube working on the principle based on the diffusion of acetylcholine chloride macromolecules. This system resembles a concentric tube, and voltage stimulation causes the transport of acetylcholine macromolecules to the outer layer where they are driven towards axon end in order to open ligand gated sodium channels and cause the transfer of current. Experiments that were performed so far were in macro scale concentration cell of which one side was filled with 0.1M acetylcholine chloride and other side with 0.1M KCl in order to detect the transport of acetylcholine molecules. Under application of only 1.0V to the system a net transfer of ions was detected. In specific time intervals samples from one side of concentration cell that contained KCl were ejected and analyzed in FTIR. Characteristic peaks of acetylcholine were found to be in 2970 and 2300 cm-1. Even in the shortest test period, acetylcholine molecules were detected on KCl side of the concentration cell, which means that under application of 1.0V a small period of time is just enough to diffuse this macromolecule through membrane. By applying 1.0 V of potential difference and testing the cell for 1 hour, 65 μA passed through the cell. Plotted graph was integrated to the charge vs. time format and obtained charge values corresponded to approximately 0.03 Coulombs/ 3600 seconds. These values were compared to actual number of transferred species. In human nerve cells, current flow through an open channel is 4pA at the membrane potential of -100mV. This corresponds to 2.49 x 107 charges s-1. Our system in macro scale concentration cell applications generates 8.33 x 10-6 A, which is nearly 5.2 x 1013 charges s-1. This logically rematches the results of actual neural cell and if we take into account the diameter of concentration cell by scaling down to standard neuron dimensions the result would approach expected values.

The remarkable point of this study is that, previous studies done in this area could obtain similar results under application of 10V and higher voltages, while we obtain quite rational results under small potential differences, which is closer to the transport process in human corporality. This study is a brand new approach to neuromodulation, which is a hot topic of 21st century and it seems to be quite consistent. Further in our studies we are aiming to make cell cultivation and perform similar tests in vivo and see if our concentric tube shaped neuromodulated device is suitable for replacing the damaged nerve cells.