A bioelectronic interface for continuous neuroinflammation monitoring and neuromodulation in Parkinson's disease...

Neuroinflammation is increasingly recognized as a critical driver in the onset and progression of Parkinson's disease (PD), yet technologies capable of continuously tracking neuroinflammatory dynamics in vivo remain limited. Here, we report an implantable bioelectronic interface that integrates multiplexed aptamer based electrochemical biosensing with deep brain stimulation (DBS) for biomarker monitoring and neuromodulation in the rat brain. The biosensing platform introduces Tantalum@Au electrodes, engineered for chronic stability and biocompatibility, enabling simultaneous in vivo electrochemical monitoring of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), α-synuclein (α-syn), and pH after DBS therapy. In freely moving PD rat models, the system maintained stable electrochemical performance for at least eight days post-implantation and captured dynamic biomarker fluctuations in response to targeted subthalamic nucleus DBS. DBS reduced IL-6 and TNF-α levels, indicating modulation of neuroinflammatory pathways, whereas α-syn level remained unchanged within the short-term window, consistent with the slower temporal dynamics of protein aggregation. DBS partially restored motor coordination though residual asymmetry persisted, paralleling clinical observations of symptom alleviation without complete functional recovery. These findings demonstrate the feasibility of integrating continuous biochemical sensing with therapeutic neuromodulation to achieve a closed-loop platform, providing direct insight into molecular responses to DBS. This bioelectronic interface establishes a foundation for future biochemical-feedback-enabled neuromodulation strategies and precision therapeutic for neurodegenerative disorders.