Targeting CD14 on blood derived cells improves intracortical microelectrode performance.

Area of Science:

• Neuroscience
• Biomaterials Science
• Immunology

Background:

• Intracortical microelectrodes are crucial for monitoring neural activity and developing brain-computer interfaces.
• Neural signal degradation over time limits the chronic performance of these devices.
• The Cluster of Differentiation 14/Toll-like receptor (CD14/TLR) pathway is a potential target for improving electrode function.

Purpose of the Study:

• To identify the specific cellular source of CD14 responsible for the decline in microelectrode recording quality.
• To determine whether targeting microglia or blood-derived macrophages offers a more effective therapeutic strategy.

Main Methods:

• Utilized a mouse bone marrow chimera model to selectively deplete CD14 in either microglia or blood-derived macrophages.
• Performed chronic single-unit recordings over 16 weeks to assess neural signal quality.
• Analyzed the impact of CD14 inhibition on intracortical microelectrode performance.

Main Results:

• Inhibiting CD14 specifically in blood-derived macrophages significantly improved intracortical microelectrode recording quality.
• Selective CD14 knockout in microglia did not yield the same performance enhancement.
• Sustained improvement in neural signal quality was observed over the 16-week study duration.

Conclusions:

• Targeting CD14 in blood-derived cells is a promising strategy to enhance the chronic performance of intracortical microelectrodes.
• Therapeutic interventions may not require crossing the blood-brain barrier, simplifying treatment delivery.
• This research provides a cellular target to improve long-term brain-computer interface functionality.