The impact of modulating the blood-brain barrier on the electrophysiological and histological outcomes of intracortical electrodes.
Journal Article (Journal Article)
Objective
Successful application of chronic intracortical electrodes remains highly variable. The biological mechanisms leading to electrode failure are still being explored. Recent work has shown a correlation between blood-brain barrier (BBB) integrity and long-term recordings. Here we proposed to modulate the BBB healing after intracortical electrode implantation, while evaluating the functional electrophysiology. The CCL2/CCR2 pathway was chosen based on previous work demonstrating the positive histological effects in an intracortical electrode model, as well as in other neurodegenerative models. By disrupting this pathway, recruitment of pro-inflammatory monocytes (a result of a breached BBB) is potentially reduced at the electrode interface.Approach
Michigan electrodes were implanted for 2 and 12 weeks in rats, and a CCR2 antagonist (RS 102895) was administered daily to the treatment group. Functional electrodes were used for the 12 week cohort, and weekly electrophysiological recordings were taken. At 2 and 12 weeks, histology was analyzed.Main results
At 12 weeks, the CCR2-antagonist group had significantly higher signal-to-noise ratios (SNRs) than control. CCR2-antagonism at 2 weeks significantly increased the neural population and decreased BBB breach. At 12 weeks, CCR2-antagonism significantly increased number of neurons and BBB + vasculature within 100 µm of the electrode interface.Significance
This work demonstrates that for intracortical electrodes, disruption of the CCL2/CCR2 pathway improves chronic outcomes in electrophysiology and histology.Full Text
Duke Authors
Cited Authors
- Falcone, JD; Sohal, HS; Kyriakides, TR; Bellamkonda, RV
Published Date
- August 2019
Published In
Volume / Issue
- 16 / 4
Start / End Page
- 046005 -
PubMed ID
- 31048574
Electronic International Standard Serial Number (EISSN)
- 1741-2552
International Standard Serial Number (ISSN)
- 1741-2560
Digital Object Identifier (DOI)
- 10.1088/1741-2552/ab1ef9
Language
- eng