The upregulation of specific interleukin (IL) receptor antagonists and paradoxical enhancement of neuronal apoptosis due to electrode induced strain and brain micromotion

摘要: The high mechanical mismatch between stiffness of silicon and metal microelectrodes soft cortical tissue, induces strain at the neural interface which likely contributes to failure interface. However, little is known about molecular outcomes electrode induced low-magnitude (1–5%) on primary astrocytes, microglia neurons. In this study we simulated brain micromotion electrode–brain by subjecting neurons cyclical using a biaxial stretch device, investigated in vitro. addition, explored functional consequence astrocytic microglial health, when they are themselves subjected strain. Quantitative real-time PCR array (qRT-PCR Array) analysis stretched astrocytes showed specific upregulation an Interleukin receptor antagonist – IL-36Ra (previously IL-1F5), ∼1018 ∼236 fold respectively. Further, gene expression remained unchanged in treated with bacterial lipopolysaccharide (LPS) indicating that observed potentially specific. Zymogram western blot revealed mechanically strained upregulated matrix metalloproteinases (MMPs) 2 9, other markers reactive gliosis such as glial fibrillary acidic protein (GFAP) neurocan compared controls. Primary without IL-36Ra, ∼400 downregulation tumor necrosis factor superfamily, member 11b (TNFRSF11b). Significant members caspase cysteine proteinase family pro-apoptotic genes was also presence than absence IL-36Ra. Adult rats implanted microwire electrodes (∼20 fold) IL-1Ra (∼1500 3 days post-implantation (3 DPI), corroborating in vitro results, although these transcripts were drastically down regulated ∼20 ∼1488 relative levels DPI, end 12 weeks (12 WPI). These results demonstrate IL antagonists may be negatively contributing neuronal health acute time-points post-electrode implantation.