Flavopiridol reduces the impedance of neural prostheses in vivo without affecting recording quality.
We hypothesized that re-entry into the cell cycle may be associated with reactive gliosis surrounding neural prostheses, and that administration of a cell cycle inhibitor (flavopiridol) at the time of surgery would reduce this effect. We investigated the effects of flavopiridol on recording quality and impedance over a 28-day time period and conducted histology at 3 and 28 days post-implantation. Flavopiridol reduced the expression of a cell cycle protein (cyclin D1) in microglia surrounding probes at the 3-day time point. Impedance at 1 kHz was decreased by drug administration across the study period compared to vehicle controls. Correlations between recording (SNR, units) and impedance metrics revealed a small, but statistically significant, inverse relationship between these variables. However, the relationship between impedance and recording quality was not sufficiently strong for flavopiridol to result in an improvement in SNR or the number of units detected. Our data indicate that flavopiridol is an effective, easily administered treatment for reducing impedance in vivo, potentially through inhibiting microglial encapsulation of implanted devices. This strategy may be useful in stimulation applications, where reduced impedance is desirable for achieving activation thresholds and prolonging the lifetime of the implanted power supply. While improvements in recording quality were not observed, a combination of flavopiridol with a second strategy which enhances neuronal signal detection may enhance these results in future studies.
Purcell
Erin K
EK
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
Thompson
David E
DE
Ludwig
Kip A
KA
Kipke
Daryl R
DR
D000704:Analysis of Variance; D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism; D055592:Biophysical Phenomena / Q000187:drug effects*; D001703:Biophysics; D001921:Brain / Q000166:cytology / Q000601:surgery; D017097:Electric Impedance; D004558:Electric Stimulation / Q000379:methods; D005419:Flavonoids / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013223:Statistics as Topic; D013997:Time Factors
D018949:Antigens, CD1; D005419:Flavonoids; D006131:Growth Inhibitors; D010880:Piperidines; C077990:alvocidib; D010751:Phosphopyruvate Hydratase