Abstract
(1) Background: Intracortical microelectrodes (IMEs) are essential to basic brain research and clinical brain–machine interfacing applications. However, the foreign body response to IMEs results in chronic inflammation and an increase in levels of reactive oxygen and nitrogen species (ROS/RNS). The current study builds on our previous work, by testing a new delivery method of a promising antioxidant as a means of extending intracortical microelectrodes performance. While resveratrol has shown efficacy in improving tissue response, chronic delivery has proven difficult because of its low solubility in water and low bioavailability due to extensive first pass metabolism. (2) Methods: Investigation of an intraventricular delivery of resveratrol in rats was performed herein to circumvent bioavailability hurdles of resveratrol delivery to the brain. (3) Results: Intraventricular delivery of resveratrol in rats delivered resveratrol to the electrode interface. However, intraventricular delivery did not have a significant impact on electrophysiological recordings over the six-week study. Histological findings indicated that rats receiving intraventricular delivery of resveratrol had a decrease of oxidative stress, yet other biomarkers of inflammation were found to be not significantly different from control groups. However, investigation of the bioavailability of resveratrol indicated a decrease in resveratrol accumulation in the brain with time coupled with inconsistent drug elution from the cannulas. Further inspection showed that there may be tissue or cellular debris clogging the cannulas, resulting in variable elution, which may have impacted the results of the study. (4) Conclusions: These results indicate that the intraventricular delivery approach described herein needs further optimization, or may not be well suited for this application.
Highlights
Intracortical microelectrode have been used for decades in basic brain research and are a critical part of neural interfacing systems designed to improve the quality of life for those with amputations, spinal cord injury, or degenerative brain diseases [1,2]
A negative binomial linear mix model showed that the interaction term for the resveratrol group was significant (p = 0.05), indicating a significantly higher slope for the resveratrol group compared to the control group
There were significantly more total units detected with the resveratrol group compared to the controls during the chronic time points, when the time points were grouped as acute and chronic
Summary
The electrodes have steadily evolved to include various materials and designs to improve biocompatibility and performance, as well as processing methods to improve neuronal activity acquisition and Micromachines 2021, 12, 1446. Failure of IMEs is often characterized by increasing noise and decreasing recorded signal amplitudes resulting in a declining signal-to-noise ratio (SNR) over time. This declining SNR results in fewer channels detecting single units and fewer single units detected per channel [12]. There are several proposed mechanisms of intracortical microelectrode failure, including mechanical breakage, biological inflammatory response, and material breakdown [10]. Oxidative stress is implicated in both the biological inflammatory response and the material breakdown— exacerbating the foreign body response of immune cells, and damaging the insulating and conducting layers of the probe itself [13,14]
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