A key to successful chronic neural interfacing is to achieve minimal glial scarring surrounding the implants, as the astrocytes and microglia may functionally insulate the interface. A possible explanation for the development of these reactions is mechanical forces arising between the implants and the brain. Here, we show that the difference between the density of neural probes and that of the tissue, and the resulting inertial forces, are key factors for the development of the glial scar. Two probes of similar size, shape, surface structure and elastic modulus but differing greatly in density were implanted into the rat brain. After six weeks, significantly lower astrocytic and microglial reactions were found surrounding the low-density probes, approaching no reaction at all. This provides a major key to design fully biocompatible neural interfaces and a new platform for in vivo assays of tissue reactions to probes with differing materials, surface structures, and shapes.

Chronic neural interfaces that are both structurally and functionally stable inside the brain over years or decades hold great promise to become an invaluable clinical tool in the near future. A main flaw in the current electrode interfaces is that their recording capabilities deteriorate over time, possibly due to lack of flexibility, which causes movements in relation to the neural tissue that result in small inflammations and loss of electrode function. We have developed a new neural probe using the stabilizing property of gelatine that allows the implantation of ultrathin and flexible electrodes into the central nervous system. The microglial and astrocytic reactions evoked by implanted gelatine needles, as well as the wire bundles in combination with gelatine, were investigated using immunohistochemistry and fluorescence microscopy up to 12 weeks after implantation. The results indicate that pure gelatine needles were stiff enough to penetrate the brain tissue on their own, and evoked a significantly smaller chronic scar than stab wounds. Moreover, gelatine embedding appeared to reduce the acute reactions caused by the implants and we found no adverse effects of gelatine or gelatine-embedded electrodes. Successful electrophysiological recordings were made from very thin electrodes implanted in this fashion.2

Chronically implanted microelectrodes are an invaluable tool for neuroscientific research, allowing long term recordings in awake and behaving animals. It is known that all such electrodes will evoke a tissue reaction affected by its’ size, shape, surface structure, fixation mode and implantation method. However, the possible correlation between tissue reactions and the number of implanted electrodes is not clear. We implanted multiple wire bundles into the brain of rats and studied the correlation between the astrocytic and microglial reaction and the positioning of the electrode in relation to surrounding electrodes. We found that an electrode implanted in the middle of a row of implants is surrounded by a significantly smaller astrocytic scar than single ones. This possible interaction was only seen between implants within the same hemisphere, no interaction with the contralateral hemisphere was found. More importantly, we found no aggravation of tissue reactions as a result of a larger number of implants. These results highlight the possibility of implanting multiple electrodes without aggravating the glial scar surrounding each implant.