Abstract
Intracortical microelectrodes record neuronal activity of individual neurons within the brain, which can be used to bridge communication between the biological system and computer hardware for both research and rehabilitation purposes. However, long-term consistent neural recordings are difficult to achieve, in large part due to the neuroinflammatory tissue response to the microelectrodes. Prior studies have identified many factors that may contribute to the neuroinflammatory response to intracortical microelectrodes. Unfortunately, each proposed mechanism for the prolonged neuroinflammatory response has been investigated independently, while it is clear that mechanisms can overlap and be difficult to isolate. Therefore, we aimed to determine whether the dual targeting of the innate immune response by inhibiting innate immunity pathways associated with cluster of differentiation 14 (CD14), and the mechanical mismatch could improve the neuroinflammatory response to intracortical microelectrodes. A thiol-ene probe that softens on contact with the physiological environment was used to reduce mechanical mismatch. The thiol-ene probe was both softer and larger in size than the uncoated silicon control probe. Cd14-/- mice were used to completely inhibit contribution of CD14 to the neuroinflammatory response. Contrary to the initial hypothesis, dual targeting worsened the neuroinflammatory response to intracortical probes. Therefore, probe material and CD14 deficiency were independently assessed for their effect on inflammation and neuronal density by implanting each microelectrode type in both wild-type control and Cd14-/- mice. Histology results show that 2 weeks after implantation, targeting CD14 results in higher neuronal density and decreased glial scar around the probe, whereas the thiol-ene probe results in more microglia/macrophage activation and greater blood–brain barrier (BBB) disruption around the probe. Chronic histology demonstrate no differences in the inflammatory response at 16 weeks. Over acute time points, results also suggest immunomodulatory approaches such as targeting CD14 can be utilized to decrease inflammation to intracortical microelectrodes. The results obtained in the current study highlight the importance of not only probe material, but probe size, in regard to neuroinflammation.
Highlights
Intracortical microelectrodes allow researchers to record singleunit and multi-unit activity from individual or groups of neurons by detecting changes to the extracellular potential as a result of neurons generating action potentials (Renshaw et al, 1940; Wessberg et al, 2000)
The current study aimed to determine whether the dual targeting of the innate immune response and the mechanical mismatch between tissue and a single-shank probe, which generates tissue damage, results in combinatorial or synergistic effects to improve neuronal density and reduce inflammation at the probe–tissue interface
The glial scar is an indicator of neuroinflammation, so glial fibrillary acidic protein (GFAP), a type of intermediate filament protein upregulated by reactive astrocytes, was examined via immunohistochemistry (Landis, 1994)
Summary
Intracortical microelectrodes allow researchers to record singleunit and multi-unit activity from individual or groups of neurons by detecting changes to the extracellular potential as a result of neurons generating action potentials (Renshaw et al, 1940; Wessberg et al, 2000). Intracortical microelectrodes are utilized in brain–computer interfacing (BCI) applications to record neural activity as an input signal to decode and extract motor intent (Schwartz, 2004; Hochberg et al, 2012). Recorded neural signal informs the generation of a desired action for an external device, prosthetic, or muscles (via muscle stimulators) for a patient suffering from paralysis or limb loss. Intracortical microelectrodes are a promising technology for both basic research and the development of clinical neuroprosthetic devices
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