Authors :
Presenting Author: Tanner Sherry, BS – Penn State University
Jiayang Liu, PhD – Postdoctoral Fellow, Neurology, Yale; Bruce Gluckman, PhD – Professor, Director Center for Neural Engineering, Engineering Science and Mechanics, Penn State University
Rationale: In recent work in animal models of epilepsy that spreading depolarization (SD) is frequently associated with – or emerges from – spontaneous seizures, the propagation rate of these waves is typically faster than induced SD. In addition, the tissue level oxygenation is NOT impaired during the seizures, although the bulk diffusion rate of O2 is decreased during seizures that end with SD. This implies a shrinking of the extracellular space that could likewise be measured with a low-frequency impedance measure.
Methods:
We leveraged the built-in lead-off detection circuitry of our amplifier to actuate a 4-wire style impedance measure changes in hippocampal tissue impedance in chronically and continuously recorded rats (N=3) made epileptic under the tetanus toxin model of temporal lobe epilepsy. Impedance actuation was applied for 4-20 days per animal respectively in this pilot study. We also designed an analysis to extract effective changes in impedance that leverages that the actuation is exactly periodic with the data sampling.
Results: In all seizures events, the impedance increased relative to the interictal baseline. Likewise, the impedance during SD was much higher than baseline, as would be expected from the cell swelling typically associated with SD. However, it appears that the primary increases in impedance occur during the seizure and not following SD initiation.
Conclusions: Increases in impedance are consistent with decreases in extracellular volume fraction. This is consistent with a mechanism for SD initiation in which extracellular potassium builds up faster due to the smaller volume. Such decreases in extracellular volume fraction are also consistent with increases in propagation speed in simple reaction diffusion models. These pilot studies indicate that careful tissue-level impedance measures can monitor locally changes in extracellular volume fraction dynamics that are relevant to understanding the complex dynamics involved in epilepsy. Likewise, because we observe local swelling related changes occurring during the seizure, that imaging techniques based on cell swelling may mis-label SD onset and propagation compared to electrophysiology and cellular firing capabilities.
Funding:
Partially funded through NIH R01-EB019804