Low frequency stimulation of ventral hippocampal commissures reduces seizures in a rat model of chronic temporal lobe epilepsy

Epilepsia. 2012 Jan;53(1):147-56. doi: 10.1111/j.1528-1167.2011.03348.x. Epub 2011 Dec 9.

Abstract

Purpose: To investigate the effects of low frequency stimulation (LFS) of a fiber tract for the suppression of spontaneous seizures in a rat model of human temporal lobe epilepsy.

Methods: Stimulation electrodes were implanted into the ventral hippocampal commissure (VHC) in a rat post-status epilepticus (SE) model of human temporal lobe epilepsy (n = 7). Two recording electrodes were placed in the CA3 regions bilaterally and neural data were recorded for a minimum of 6 weeks. LFS (60 min train of 1 Hz biphasic square wave pulses, each 0.1 ms in duration and 200 μA in amplitude, followed by 15 min of rest) was applied to the VHC for 2 weeks, 24 h a day.

Key findings: The baseline mean seizure frequency of the study animals was 3.7 seizures per day. The seizures were significantly reduced by the application of LFS in every animal (n = 7). By the end of the 2-week period of stimulation, there was a significant, 90% (<1 seizure/day) reduction of seizure frequencies (p < 0.05) and a 57% reduction during the period following LFS (p < 0.05) when compared to baseline. LFS also resulted in a significant reduction of hippocampal interictal spike frequency (71%, p < 0.05), during 2 weeks of LFS session. The hippocampal histologic analysis showed no significant difference between rats that received LFS and SE induction and those that had received only SE-induction. None of the animals showed any symptomatic hemorrhage, infection, or complication.

Significance: Low frequency stimulation applied at a frequency of 1 Hz significantly reduced both the excitability of the neural tissue as well as the seizure frequency in a rat model of human temporal lobe epilepsy. The results support the hypothesis that LFS of fiber tracts can be an effective method for the suppression of spontaneous seizures in a temporal lobe model of epilepsy in rats and could lead to the development of a new therapeutic modality for human patients with temporal lobe epilepsy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA3 Region, Hippocampal / physiopathology*
  • Disease Models, Animal
  • Electric Stimulation / methods*
  • Electric Stimulation Therapy / methods*
  • Electrodes, Implanted
  • Electroencephalography
  • Epilepsy, Temporal Lobe / physiopathology
  • Epilepsy, Temporal Lobe / therapy*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / physiopathology
  • Seizures / therapy*
  • Treatment Outcome