Pro-myelinating Clemastine administration improves recording performance of chronically implanted microelectrodes and nearby neuronal health

by Selleckchem | Mar 09 2023

Intracortical microelectrodes have become a useful tool in neuroprosthetic applications in the clinic and to understand neurological disorders in basic neurosciences. Many of these brain-machine interface technology applications require successful long-term implantation with high stability and sensitivity. However, the intrinsic tissue reaction caused by implantation remains a major failure mechanism causing loss of recorded signal quality over time. Oligodendrocytes remain an underappreciated intervention target to improve chronic recording performance. These cells can accelerate action potential propagation and provides direct metabolic support for neuronal health and functionality. However, implantation injury causes oligodendrocyte degeneration and leads to progressive demyelination in surrounding brain tissue. Previous work highlighted that healthy oligodendrocytes are necessary for greater electrophysiological recording performance and the prevention of neuronal silencing around implanted microelectrodes over chronic implantation. Thus, we hypothesize that enhancing oligodendrocyte activity with a pharmaceutical drug, Clemastine, will prevent the chronic decline of microelectrode recording performance. Electrophysiological evaluation showed that the promyelination Clemastine treatment significantly elevated the signal detectability and quality, rescued the loss of multi-unit activity, and increased functional interlaminar connectivity over 16-weeks of implantation. Additionally, post-mortem immunohistochemistry showed that increased oligodendrocyte density and myelination coincided with increased survival of both excitatory and inhibitory neurons near the implant. Overall, we showed a positive relationship between enhanced oligodendrocyte activity and neuronal health and functionality near the chronically implanted microelectrode. This study shows that therapeutic strategy that enhance oligodendrocyte activity is effective for integrating the functional device interface with brain tissue over chronic implantation period.

Comments：

It's fascinating to see how improving oligodendrocyte activity with a pharmaceutical drug like Clemastine can prevent the chronic decline of microelectrode recording performance. It's interesting to note that healthy oligodendrocytes are necessary for greater electrophysiological recording performance and the prevention of neuronal silencing around implanted microelectrodes over chronic implantation. By promoting oligodendrocyte activity with Clemastine, the researchers were able to increase the survival of both excitatory and inhibitory neurons near the implant and improve functional interlaminar connectivity over 16 weeks of implantation. This study shows the potential for therapeutic strategies that enhance oligodendrocyte activity in improving the integration of functional device interfaces with brain tissue over a long period of time.