Piezo1 and Piezo2 Ion Channels in Neuronal and Astrocytic Responses to MEA Implants in the Rat Somatosensory Cortex

Intracortical microelectrode arrays (MEAs) are tools for recording and stimulating neural activity, with potential applications in prosthetic control and treatment of neurological disorders. However, when chronically implanted, the long-term functionality of MEAs is hindered by the foreign body response (FBR), characterized by gliosis, neuronal loss, and the formation of a glial scar encapsulating layer. This response begins immediately after implantation and is exacerbated by factors such as brain micromotion and the mechanical mismatch between stiff electrodes and soft brain tissue, leading to signal degradation. Despite progress in mitigating these issues, the underlying mechanisms of the brain's response to MEA implantation remain unclear, particularly regarding how cells sense and respond to the associated mechanical forces. Mechanosensitive ion channels, such as the Piezo family, are key mediators of cellular responses to mechanical stimuli. In this study, silicon-based NeuroNexus MEAs consisting of four shanks were implanted in the rat somatosensory cortex for sixteen weeks. Weekly neural recordings were conducted to assess signal quality over time, revealing a decline in active electrode yield and signal amplitude. Immunohistochemical analysis showed an increase in GFAP intensity and decreased neuronal density near the implant site. Furthermore, Piezo1-but not Piezo2-was strongly expressed in GFAP-positive astrocytes within 25 µm of the implant. Piezo2 expression appeared relatively uniform within each brain slice, both in and around the MEA implantation site across cortical layers. Our study builds on previous work by demonstrating a potential role of Piezo1 in the chronic FBR induced by MEA implantation over a 16-week period. Our findings highlight Piezo1 as the primary mechanosensitive channel driving chronic FBR, suggesting it may be a target for improving MEA design and long-term functionality.