Differential Expression of Genes Involved in the Chronic Response to Intracortical Microelectrodes

Song, Sydney; Druschel, Lindsey; Chan, RV Paul; Capadona, Jeffrey R.

doi:10.2139/ssrn.4354683

Cited by 6 publications

(9 citation statements)

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“…However, the drug may also be swapped out for any therapeutic designed to improve brain tissue health and function. The flexibility of our design lends itself ‘flexible’ to the discovery of additional targets with the recent use of more sophisticated analysis methods of the neuroinflammatory response to IMEs [ 13 , 77 , 78 , 79 , 80 , 81 , 82 ]. The ability for this probe to be a platform device makes it a powerful tool that may help improve patient quality of life.…”

Section: Discussionmentioning

confidence: 99%

Fabrication Methods and Chronic In Vivo Validation of Mechanically Adaptive Microfluidic Intracortical Devices

Kim,

Mueller,

Schwartzman

et al. 2023

Micromachines

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Intracortical neural probes are both a powerful tool in basic neuroscience studies of brain function and a critical component of brain computer interfaces (BCIs) designed to restore function to paralyzed patients. Intracortical neural probes can be used both to detect neural activity at single unit resolution and to stimulate small populations of neurons with high resolution. Unfortunately, intracortical neural probes tend to fail at chronic timepoints in large part due to the neuroinflammatory response that follows implantation and persistent dwelling in the cortex. Many promising approaches are under development to circumvent the inflammatory response, including the development of less inflammatory materials/device designs and the delivery of antioxidant or anti-inflammatory therapies. Here, we report on our recent efforts to integrate the neuroprotective effects of both a dynamically softening polymer substrate designed to minimize tissue strain and localized drug delivery at the intracortical neural probe/tissue interface through the incorporation of microfluidic channels within the probe. The fabrication process and device design were both optimized with respect to the resulting device mechanical properties, stability, and microfluidic functionality. The optimized devices were successfully able to deliver an antioxidant solution throughout a six-week in vivo rat study. Histological data indicated that a multi-outlet design was most effective at reducing markers of inflammation. The ability to reduce inflammation through a combined approach of drug delivery and soft materials as a platform technology allows future studies to explore additional therapeutics to further enhance intracortical neural probes performance and longevity for clinical applications.

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Section: Discussionmentioning

confidence: 99%

Fabrication Methods and Chronic In Vivo Validation of Mechanically Adaptive Microfluidic Intracortical Devices

Kim,

Mueller,

Schwartzman

et al. 2023

Micromachines

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“…262,263 Ultimately, probes intended to directly interface with neural tissue are slowly segregated from the CNS as glial scar tissue encapsulates the electrode shank. 264 Thus, regulating neuroinflammatory signaling and glial reactivity to the implant is critical for ensuring the long-term reliability of implanted probes. Two approaches exist in choosing materials for the fabrication of neural probes and their coatings.…”

Section: Neural Probe Coatingsmentioning

confidence: 99%

Biomaterial strategies for regulating the neuroinflammatory response

Galindo,

Frey Rubio,

Hettiaratchi

2024

Mater. Adv.

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“…Neuroin ammation has long been associated with intracortical microelectrode failure 3,16,38 . Here, we utilized one of the most advanced methods reported to date to assess the intracortical microelectrodetissue interface, both spatial proteomics (with and without cell speci city) 39 , and spatially-resolved whole mouse transcriptomics 40,41 . Our goal was to begin to understand the potential relationship between invasive microbes in the brain, neuroin ammation, and microelectrode recording performance.…”

Section: Antibiotic Treatment Impacts the Neuroin Ammatory Response T...mentioning

confidence: 99%

“…Raw proteomic counts from the neural proteomic panel were uploaded and analyzed using a custom MATLAB R2021a script, following previously established protocols 39 . First, the negative and positive spike-in proteins were removed from analysis.…”

Section: Spatial Proteomic Analysis Of the Implant Sitementioning

confidence: 99%

Bacteria Invade the Brain Following Sterile Intracortical Microelectrode Implantation

Capadona,

Hoeferlin,

Grabinski

et al. 2024

Preprint

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Brain-machine interface performance is largely affected by the neuroinflammatory responses resulting in large part from blood-brain barrier (BBB) damage following intracortical microelectrode implantation. Recent findings strongly suggest that certain gut bacterial constituents penetrate the BBB and are resident in various brain regions of rodents and humans, both in health and disease. Therefore, we hypothesized that damage to the BBB caused by microelectrode implantation could amplify dysregulation of the microbiome-gut-brain axis. Here, we report that bacteria, including those commonly found in the gut, enter the brain following intracortical microelectrode implantation in mice implanted with single-shank silicon microelectrodes. Systemic antibiotic treatment of mice implanted with microelectrodes to suppress bacteria resulted in differential expression of bacteria in the brain tissue and a reduced acute inflammatory response compared to untreated controls, correlating with temporary improvements in microelectrode recording performance. Long-term antibiotic treatment resulted in worsening microelectrode recording performance and dysregulation of neurodegenerative pathways. Fecal microbiome composition was similar between implanted mice and an implanted human, suggesting translational findings. However, a significant portion of invading bacteria was not resident in the brain or gut. Together, the current study established a paradigm-shifting mechanism that may contribute to chronic intracortical microelectrode recording performance and affect overall brain health following intracortical microelectrode implantation.

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Differential Expression of Genes Involved in the Chronic Response to Intracortical Microelectrodes

Cited by 6 publications

References 0 publications

Fabrication Methods and Chronic In Vivo Validation of Mechanically Adaptive Microfluidic Intracortical Devices

Fabrication Methods and Chronic In Vivo Validation of Mechanically Adaptive Microfluidic Intracortical Devices

Biomaterial strategies for regulating the neuroinflammatory response

Bacteria Invade the Brain Following Sterile Intracortical Microelectrode Implantation

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