Long-term multi-dimensional neural probes for electrochemical detection of biomarkers in brain disorders – 3-DBrain

Neural prostheses offer promising perspectives to restore motor functions and communication capabilities in patients suffering from severe paralysis or neurodegenerative diseases. These approaches require the use of implanted electrodes offering the possibility to simulate or record brain activity with stability on the long term. Unfortunately, despite the great promise for future therapeutic treatments, the implementation of intra-cortical single neuron recordings is limited today by the loss of neural recordings over time after implantation. Indeed, sustained inflammatory processes in the central nervous system (CNS) caused by the foreign body response with time impairs the mechanical and electrical stability of the implanted electrodes. Recent studies have suggested that failure is due, at least in part, to loss of neurons within the recording zone immediately adjacent to the microelectrode. During insertion, rigid microelectrodes mechanically damage the membranes of neurons and glial cells alike. Intracellular proteins and active compounds are then released into the extracellular environment and trigger an acute inflammatory response around the microelectrode. More specifically, microglia, oligodendrocyte precursors and astrocytes release signaling inflammatory mediators such as pro-histamine, inflammatory cytokines and other active compounds into the local environment initiating a cascade of events that leads to glial cell proliferation, and this inflammation is accompanied by neurodegeneration, thereby compromising the stability of recorded signals on the timescale of weeks to months. To date, however, no studies have examined strategies that directly repair and/ or prevent the damage due to the electrode insertion in-vivo. Such long-term capabilities are today critically important in treating disorders of the CNS and neurological disorders such as epilepsy, Parkinson’s disease, depression or chronic pain. Overcoming these long-term limitations requires greater attention to the importance of the electrode-tissue interfaces, matching of overall probe/tissue mechanical properties and a better understanding of the biological mechanisms involved in the modulation of innate immune responses. The 3DBain project aims to elucidate the issues of long-term stability of chronic neural implants. Our approach involves the realization of multi-dimensional (2D and 3D) brain probes that combines flexibility and cellular/subcellular designs to allow a better interpenetration of neurons with microelectronics. The overarching goal will be to demonstrate the utility of the probe by addressing the role of simultaneously recording electrophysiology signals and extracellular compounds directly involved in the modulation of immune responses. This novel technology will be developed to interface with the complex environment of the brain for more advanced experimental investigations at the intersections of neurophysiology and neuropathology. The validation experiments will be conducted using relevant in vitro and in vivo testbeds as a scientific foundation for long-term research work to more fully understand neurological damages/disorders.