Transcriptomic analysis of the physiological responses to injuries induced accompanying intracortical microelectrode...

The neuroinflammatory response to intracortical microelectrodes (IMEs) is regarded as a major contributor to device performance degradation and failure. Iatrogenic injuries from the craniotomy, IME insertion, and the continued presence of the implanted device all evoke a temporally mediated neuroinflammatory response. Transcriptomic analyses have emerged as a highly sensitive and detailed approach to characterizing and quantifying the neuroinflammatory response to IME implantation. Therefore, we used transcriptomic analyses to update the historic characterization of the component injuries associated with IME devices to differentiate surgical and device-related contributions to neuroinflammation and provide an updated view of a decades-old problem. Four injury profiles - uninjured, craniotomy-only, stab wound, and implant - were applied to each rat in different locations corresponding to traditional IME placement. At 2, 8, or 16 weeks after surgery, tissue was extracted and processed using bulk transcriptomic analysis with a custom panel of 212 genes related to neuroinflammation and neuronal health. Many genes were significantly differentially expressed compared to naïve controls across time points, with highly similar gene and pathway profiles observed across the craniotomy-only, stab wound, and implant groups. Additionally, the uninjured tissue region also exhibited neuroinflammation-related gene expression changes. The results presented here suggest that the neuroinflammatory response due to the intracortical implant can extend to distal brain regions. The persistent and widespread neuroinflammatory response indicates a need for novel strategies to minimize the iatrogenic effects of neural implants and suggests that the placement of additional implants for increased tissue access may come at the cost of exacerbating neuroinflammation.