Mechanical flexibility reduces the foreign body response to long-term implanted microelectrodes in rabbit cortex

Sohal, Harbaljit S.; Clowry, G. J.; Jackson, Andrew; O’Neill, Anthony; Baker, Stuart N.

doi:10.1101/058982

Cited by 20 publications

(20 citation statements)

References 25 publications

(31 reference statements)

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“…Presence of CD3 and l-Ab, molecules associated with inflammation, was determined by immunohistochemistry. No significant differences in either CD3 or l-Ab staining were found between non-implanted and implanted nerve areas (Figure 6) as determined by normalised radial distribution analysis extending 150 um from the cross-sectional nerve center [18]. The limited inflammatory response observed indicates high biocompatibility of the implanted microelectrode.…”

Section: Resultsmentioning

confidence: 99%

“…Images were analysed in the Matlab environment (2014b Mathworks, USA) as previously described [18]. In brief, image intensities were normalized to the endogenous background staining for each slide.…”

Section: Methodsmentioning

confidence: 99%

“…A microfabrication process was already developed for flexible, highly biocompatible probes intended for intracortical use and capable of stably recording electrical activity in the rabbit cortex for a period exceeding two years [16–18]. To our knowledge, this technology has not yet been implemented for interfacing with peripheral nerves.…”

Section: Introductionmentioning

confidence: 99%

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A novel flexible cuff-like microelectrode for dual purpose, acute and chronic electrical interfacing with the mouse cervical vagus nerve

et al. 2017

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Objective. Neural reflexes regulate immune response and homeostasis. Advances in bioelectronic medicine indicate that electrical stimulation of the vagus nerve can be used to treat inflammatory disease, yet the understanding of neural signals that regulate inflammation is incomplete. Current interfaces with the vagus nerve do not permit effective chronic stimulation or recording in mouse models, which is vital to studying the molecular and neurophysiological mechanisms that control inflammation homeostasis in health and disease. Here, we developed an implantable, dual purpose multi-channel, flexible electrode array, a “microelectrode”, for recording and stimulation of the mouse vagus nerve. Approach. The array was microfabricated on an 8 μm layer of highly biocompatible parylene configured with 16 sites. The microelectrode was evaluated by studying the recording and stimulation performance. Mice were chronically implanted with devices for up to 12 weeks. Main Results. Using the microelectrode in vivo, high fidelity signals were recorded during physiological challenges (e.g potassium chloride and interleukin-1 β), and electrical stimulation of the vagus nerve produced the expected significant reduction of blood levels of tumor necrosis factor (TNF) in endotoxemia. Inflammatory cell infiltration at the microelectrode implantation at 12 weeks of implantation was limited in our radial distribution analysis of inflammatory cell. Significance. This novel device provides an important step towards a viable chronic interface for cervical vagus nerve stimulation and recording in mice for both acute and chronic applications.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A novel flexible cuff-like microelectrode for dual purpose, acute and chronic electrical interfacing with the mouse cervical vagus nerve

et al. 2017

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“…ED-1-microglia, GFAP-Astrocytes, IgG-blood brain barrier integrity) can be used to determine the integrity of the tissue (Polikov, Tresco and Reichert, 2005;Nolta et al, 2015;Sohal et al, 2016;Falcone et al, 2019). This combined with chronic electrophysiology and impedance measurements will be indicative of the electrode performance with laser ablation of the pia used as a method for insertion.…”

Section: Histologymentioning

confidence: 99%

Laser Ablation of the Pia Mater for Insertion of High-Density Microelectrode Arrays in a Translational Sheep Model

Boergens

Tadić

Hopper

et al. 2020

Preprint

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The safe insertion of high density intracortical electrode arrays has been a long-standing practical challenge for neural interface engineering and applications such as brain-computer interfaces (BCIs). Here we describe a surgical procedure, inspired by laser corneal ablation, that can be used in large mammals to thin the pia mater, the innermost meningeal layer encapsulating the brain. This procedure allows for microelectrode arrays to be inserted into the cortex with less force, thus reducing deformation of underlying tissue during placement of the microelectrodes. We demonstrate that controlled pia removal over a small area of cortex allows for insertion of high-density electrode arrays and subsequent acute recordings of spiking neuron activity in sheep cortex. We also show histological and electrophysiological evidence that laser removal of the pia does not acutely affect neuronal viability in the region. This approach suggests a promising new path for clinical BCI with high-density microelectrode arrays.

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“…Analysis of the neuroinflammatory response in post-implantation tissues can be accomplished using various histological techniques. There are dozens of groups actively working in this area and each has developed slightly different methods for their analyses (McCreery et al, 2016;Potter et al, 2012a, b;Sohal et al, 2016;Oakes et al, 2018;Lo et al, 2018). Histology can be used to categorize inflammatory markers based on their relative distance from the resulting hole after explanting the microelectrode implant in order to gain a greater understanding of the spatial reach of the neuroinflammatory response to implantation.…”

Section: Introductionmentioning

confidence: 99%

A graphical user interface to assess the neuroinflammatory response to intracortical microelectrodes

Lindner

Capadona

et al. 2019

Journal of Neuroscience Methods

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Background: Brain-implanted devices, including intracortical microelectrodes, are used in neuroscience applications ranging from research to rehabilitation and beyond. Significant efforts are focused on developing new device designs and insertion strategies that mitigate initial trauma and subsequent neuroinflammation that occurs as a result of implantation. A frequently published metric is the neuroinflammatory response quantified as a function of distance from the interface edge, using fluorescent immunohistochemical markers. New method: Here, we sought to develop a graphical user interface software in Matlab to provide an objective, repeatable, and easy-to-use method for analyzing fluorescence immunohistochemistry images of neuroinflammation. The user interface allows for efficient batchprocessing and review of images, and incorporates zoom and contrast features to improve the accuracy of identifying the 'region of interest' (ROI). Results: The software was validated against previously published results and demonstrated equivalent scientific conclusions. Furthermore, a comparison between novice and expert users demonstrated consistency across levels of training and a rapid learning-curve. Comparison with existing method(s): Existing methods published in the intracortical microelectrode literature include a wide variety of procedures within ImageJ and Matlab. However, specific procedural details are often lacking. Conclusions: The distribution of the methodology may promote efficiency and reproducibility across the field seeking to characterize the tissue response to implanted neural interfaces. It may also serve as a template for researchers seeking to perform other types of histological quantification as a function of distance from an ROI.

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Mechanical flexibility reduces the foreign body response to long-term implanted microelectrodes in rabbit cortex

Cited by 20 publications

References 25 publications

A novel flexible cuff-like microelectrode for dual purpose, acute and chronic electrical interfacing with the mouse cervical vagus nerve

A novel flexible cuff-like microelectrode for dual purpose, acute and chronic electrical interfacing with the mouse cervical vagus nerve

Laser Ablation of the Pia Mater for Insertion of High-Density Microelectrode Arrays in a Translational Sheep Model

A graphical user interface to assess the neuroinflammatory response to intracortical microelectrodes

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