In vivoelectrochemical characterization and inflammatory response of multiwalled carbon nanotube-based electrodes in rat hippocampus

Abstract

Stimulating neural electrodes are required to deliver charge to an environment that presents itself as hostile. The electrodes need to maintain their electrical characteristics (charge and impedance) in vivo for a proper functioning of neural prostheses. Here we design implantable multi-walled carbon nanotubes coating for stainless steel substrate electrodes, targeted at wide frequency stimulation of deep brain structures. In well-controlled, low-frequency stimulation acute experiments, we show that multi-walled carbon nanotube electrodes maintain their charge storage capacity (CSC) and impedance in vivo. The difference in average CSCs (n = 4) between the in vivo (1.111 mC cm(-2)) and in vitro (1.008 mC cm(-2)) model was statistically insignificant (p > 0.05 or P-value = 0.715, two tailed). We also report on the transcription levels of the pro-inflammatory cytokine IL-1beta and TLR2 receptor as an immediate response to low-frequency stimulation using RT-PCR. We show here that the IL-1beta is part of the inflammatory response to low-frequency stimulation, but TLR2 is not significantly increased in stimulated tissue when compared to controls. The early stages of neuroinflammation due to mechanical and electrical trauma induced by implants can be better understood by detection of pro-inflammatory molecules rather than by histological studies. Tracking of such quantitative response profits from better analysis methods over several temporal and spatial scales. Our results concerning the evaluation of such inflammatory molecules revealed that transcripts for the cytokine IL-1beta are upregulated in response to low-frequency stimulation, whereas no modulation was observed for TLR2. This result indicates that the early response of the brain to mechanical trauma and low-frequency stimulation activates the IL-1beta signaling cascade but not that of TLR2.

Implantable Electrodes with Carbon Nanotube Coatings

“…Tracking of inflammatory response in vivo is of importance if the objective of the implant is charge transfer. We have demonstrated that certain inflammatory molecules, initially active at the electrode-nervous tissue interface, do not prevent charge transfer neither increase the impedance of MWCNT electrodes in acute implants (Minnikanti et al, 2010). This effect of molecular interaction occurring at the interface of MWCNTs and neural tissue needs to be further investigated.…”

“…However, stability of conductive polymers is questionable (Ansaldo et al, 2011;Peixoto et al, 2009). CNTs, with their distinctive properties, can improve the performance of NE, as a coating over the metallic electrodes (Minnikanti et al, 2010) or when electrochemically co-deposited with conductive polymers (Keefer et al, 2008).…”

“…We have tested the same deposition method with different substrates, and all of them kept their characteristic reduction-oxidation peaks upon MWCNT deposition. Those CNT electrodes present an interesting in vivo behavior: they maintained their CSC in vivo and in vitro in acute scenarios (Minnikanti et al, 2010). The inflammatory response from the tissue hinders the charge transfer in acute and chronic situations.…”

“…The authors conclude that the CVD deposited CNT is the best electrode in terms of robustness, but the use of high quantities of nickel will prevent the chronic use of these electrodes. Our group developed electrophoretically deposited MWCNT electrodes, with the explicit requirement of wide frequency stimulation of deep brain structures (Minnikanti et al, 2010). We conducted acute implants in the rodent hippocampus to evaluate the in vivo performance of the MWCNT electrodes, and to compare that performance with the in vitro results.…”

“…For the bare stainless steel electrode, CSCc = 0.488 mC cm −2 ; for the MWCNT-coated electrode, CSCc = 0.996 mC cm − 2 . Reprinted with permission from (Minnikanti et al, 2010). Copyright (2010) Institue of Physics.…”