Control and Effect of Glial Cell Activation on the Microscale Chronic Neural Interface toward Dynamic Control of Neural Environment.

Abstract

The limited lifetime of neural implants continues to frustrate the progress of neuroscience research. Despite extensive research into the inflammatory process and the encapsulation cascade, there has been little attention to when functional degradation of the neural probe actually begins. However, the initiation point is critical in determining the optimal time to intervene in the encapsulation process. If onset of signal degradation occurs at the very early stages of encapsulation, inhibition agents could be introduced to prevent glial activation. On the other hand, if onset occurs later in the encapsulation process it might be more advantageous to interrupt the inflammatory process before the formation of scar tissue. To answer these questions, we developed in vitro models for injury (thrombin/scratch) and acute inflammatory response (lypopolysaccride, LPS) to investigate the correlation between increasing signal impedance and the activation of glial cells. Using these in vitro models to monitor the impedance of the activated cells, we were able to demonstrate the increased impedance of activated glial cells compared to inactivated cells. This finding suggests that once an optimal strategy to intervene in encapsulation is developed, it should be possible to get stable long term recording/stimulation by controlling encapsulation at acceptable levels. We proved this concept of dynamic control, testing sequential activation/deactivation of glial cells to investigate: 1) if controlling glial activation levels over a short period of time is possible, and 2) the effect of the change of the activation levels on probe functionality by monitoring impedance. The critical implications of our results are that glial activation can be controlled in short periods of time and, hence, the impedance of the probe can be controlled by controlling the activation of the glial cells surrounding the probe.