title: In vivo polymerization of poly(3,4-ethylenedioxythiophene) in the living rat hippocampus does not cause a significant loss of performance in a delayed alternation task.
abstract: After extended implantation times, traditional intracortical neural probes exhibit a foreign-body reaction characterized by a reactive glial sheath that has been associated with increased system impedance and signal deterioration. Previously, we have proposed that the local in vivo polymerization of an electronically and ionically conducting polymer, poly(3,4-ethylenedioxythiophene) (PEDOT), might help to rebuild charge transport pathways across the glial scar between the device and surrounding parenchyma (Richardson-Burns et al 2007 J. Neural Eng. 4 L6-13). The EDOT monomer can be delivered via a microcannula/electrode system into the brain tissue of living animals followed by direct electrochemical polymerization, using the electrode itself as a source of oxidative current. In this study, we investigated the long-term effect of local in vivo PEDOT deposition on hippocampal neural function and histology. Rodent subjects were trained on a hippocampus-dependent task, delayed alternation (DA), and implanted with the microcannula/electrode system in the hippocampus. The animals were divided into four groups with different delay times between the initial surgery and the electrochemical polymerization: (1) control (no polymerization), (2) immediate (polymerization within 5 min of device implantation), (3) early (polymerization within 3-4 weeks after implantation) and (4) late (polymerization 7-8 weeks after polymerization). System impedance at 1 kHz was recorded and the tissue reactions were evaluated by immunohistochemistry. We found that under our deposition conditions, PEDOT typically grew at the tip of the electrode, forming an ∼500 µm cloud in the tissue. This is much larger than the typical width of the glial scar (∼150 µm). After polymerization, the impedance amplitude near the neurologically important frequency of 1 kHz dropped for all the groups; however, there was a time window of 3-4 weeks for an optimal decrease in impedance. For all surgery-polymerization time intervals, the polymerization did not cause significant deficits in performance of the DA task, suggesting that hippocampal function was not impaired by PEDOT deposition. However, GFAP+ and ED-1+ cells were also found at the deposition two weeks after the polymerization, suggesting potential secondary scarring. Therefore, less extensive deposition or milder deposition conditions may be desirable to minimize this scarring while maintaining decreased system impedance.
authors: Department of Materials Science and Engineering, University of Delaware, Newark, DE 19716, USA.
authors: Liangqi
authors: L
authors: Ouyang
authors: Crystal L
authors: CL
authors: Shaw
authors: Chin-Chen
authors: CC
authors: Kuo
authors: Amy L
authors: AL
authors: Griffin
authors: David C
authors: DC
authors: Martin
mesh_terms: D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage* / Q000378:metabolism; D004567:Electrodes, Implanted; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D058105:Polymerization; D011108:Polymers / Q000008:administration & dosage* / Q000378:metabolism; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D013997:Time Factors
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D011108:Polymers; C121383:poly(3,4-ethylene dioxythiophene)