Research ArticleHEALTH AND MEDICINE

Electrophoretic drug delivery for seizure control

See allHide authors and affiliations

Science Advances  29 Aug 2018:
Vol. 4, no. 8, eaau1291
DOI: 10.1126/sciadv.aau1291
  • Fig. 1 Overview of the μFIP probe.

    (A) Implanted end of the device (inset scale bar, 100 μm; outside scale bar, 1 mm). (B) Net transported charge across the ion bridge when actively pumping GABA at 1 V (line, left axis), [GABA] passively diffused out of the device when no voltage was applied (open symbols, right axis), and [GABA] actively pumped out of the device at 1 V (closed symbols, right axis). (C) Schematic showing placement of syringe for 4AP injection, Si depth probe, and the μFIP probe in the hippocampus. (D) Conceptual illustration showing a proposed effect of 4AP on K+ channels and action potentials (31) along with the analogous effects of GABA. (E) Representative recording of intense SLEs following injection of 4AP at two different time scales.

  • Fig. 2 Representative electrophysiology recordings from the hippocampus.

    (A) Recording in the absence of the μFIP treatment with SLEs starting approximately 30 min after 4AP injection followed by status epilepticus. (B) Recording of case in which the μFIP treatment was initiated immediately following the first SLE, showing no further pathological events after the treatment starts. (C) Recording in which the μFIP treatment was initiated before 4AP injection, showing no pathological events. Red arrow indicates 4AP injection. Solid green arrows indicate start of the μFIP treatment, and open green arrows mark the end of the μFIP treatment. Sharp peaks at 100-s intervals following green arrow are artifacts from the μFIP treatment.

  • Fig. 3 Frequency of pathological activity recorded for control experiments with only 4AP as well as for the case of delivering GABA after 4AP and the case of GABA before 4AP.
  • Fig. 4 Representative recording from an anesthetized mouse given a 4AP injection during a period of GABA delivery (solid green arrow until open green arrow) followed by a second 4AP dose administered several minutes after the μFIP treatment was stopped.

    Time/frequency plots for periods before (top left), during (bottom left), and after GABA delivery (bottom right) as well as during an SLE event (top right) are shown along with recording windows for shorter time scales. Dashed lines indicate the time periods covered by each time/frequency and recording plot.

  • Fig. 5 Representative histological evaluation of implant traces.

    (A) μFIP implant, (B) 4AP syringe, and (C) multichannel Si electrode in the hippocampus. The implants were labeled with DiI and shown as red traces. Astrocytes were labeled in green [glial fibrillary acidic protein (GFAP)], while all cellular nuclei were stained in blue [4′,6-diamidino-2-phenylindole (DAPI)]. Major regions of the hippocampus were labeled in white [cornu ammonis 1 (CA1), cornu ammonis 3 (CA3), and dentate gyrus (DG)]. Scale bar, 500 μm.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/4/8/eaau1291/DC1

    Fig. S1. Overview of basic fabrication steps and materials used to make μFIP probes.

    Fig. S2. Low-magnification image of the coronal sections of the brain containing the three devices.

    Table S1. Frequency of pathological activity from in vivo experiments.

  • Supplementary Materials

    This PDF file includes:

    • Fig. S1. Overview of basic fabrication steps and materials used to make μFIP probes.
    • Fig. S2. Low-magnification image of the coronal sections of the brain containing the three devices.
    • Table S1. Frequency of pathological activity from in vivo experiments.

    Download PDF

    Files in this Data Supplement:

Stay Connected to Science Advances

Navigate This Article