Investigation of the Feasibility of Ventricular Delivery of Resveratrol to the Microelectrode Tissue Interface

Authors

Youjoung Kim, Case Western Reserve UniversityFollow
Evon S. Ereifej, Case Western Reserve University
William E. Schwartzman, Case Western Reserve UniversityFollow
Seth M. Meade, Case Western Reserve UniversityFollow
Keying Chen, Case Western Reserve UniversityFollow
Jacob M. Rayyan, Case Western Reserve UniversityFollow
He Feng, Case Western Reserve UniversityFollow
Varoon Aluri, Case Western Reserve UniversityFollow
Natalie N. Mueller, Case Western Reserve UniversityFollow
Raman Bhambra, Case Western Reserve University
Sahaj Bhambra, Case Western Reserve UniversityFollow
Dawn M. Taylor, Case Western Reserve UniversityFollow
Jeffrey R. Capadona, Case Western Reserve UniversityFollow

Author ORCID Identifier

Youjoung Kim

Evon S. Ereifej

Seth M. Meade

Natalie N. Mueller

Varoon Aluri

Jeffrey R. Capadona

Document Type

Article

Publication Date

11-25-2021

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, intraventricu-lar 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 signifi-cantly 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.

Keywords

antioxidant, foreign body response, intracortical microelectrode, neural, neural recording, ventricular drug delivery

Publication Title

Micromachines

Rights

© 2021 by the authors.

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Kim, Y.; Ereifej, E.S.; Schwartzman, W.E.; Meade, S.M.; Chen, K.; Rayyan, J.; Feng, H.; Aluri, V.; Mueller, N.N.; Bhambra, R.; et al. Investigation of the Feasibility of Ventricular Delivery of Resveratrol to the Microelectrode Tissue Interface. Micromachines 2021, 12, 1446. https://doi.org/10.3390/mi12121446