Termination of epileptiform activity by cooling in rat hippocampal slice epilepsy models

Gholam K. Motamedi, Patricia Salazar, Eric L. Smith, Ronald P. Lesser, William R S Webber, Pavel I. Ortinski, Stefano Vicini, Michael A Rogawski

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Cooling has been shown to terminate experimentally induced epileptiform activity in models of epilepsy without causing injury to the cooled brain, suggesting that cooling could represent an approach to seizure control in intractable focal epilepsies. Here we sought to determine the most effective way to apply cooling to abort spontaneous epileptiform discharges in in vitro brain slice models. We induced spontaneous epileptiform activity in rat brain slices by exposure to 4-aminopyridine (4-AP), 4-AP plus bicuculline, and Mg2+-free artificial CSF (aCSF) at 28-34 °C. Extracellular field recordings were made at hippocampal or neocortical sites. Slice temperature was reduced by perfusion with cold aCSF. Rapid cooling at rates of 2-5 °C/s was compared to cooling at slower rates of 0.1-1 °C/s. Cooling at both rates reversibly aborted epileptiform discharges in all three models and at all recording sites. With rapid cooling, small temperature drops were highly effective in terminating discharges, an effect that was sustained for as long as the reduced temperature level was maintained. In contrast, slow cooling required much larger temperature drops to inhibit discharges. With slow cooling, absolute temperature drops to 21-22 °C caused a 90% reduction in event frequency, but cooling to 14-15 °C was required to terminate discharges. We conclude that rapid cooling as effectively aborts discharges in in vitro epilepsy models as does slow cooling, but the magnitude of the temperature change required is less. Practical devices to inhibit seizure activity may only need to induce small temperature drops, if the cooling can be applied sufficiently rapidly.

Original languageEnglish (US)
Pages (from-to)200-210
Number of pages11
JournalEpilepsy Research
Volume70
Issue number2-3
DOIs
StatePublished - Aug 2006
Externally publishedYes

Fingerprint

Epilepsy
Temperature
4-Aminopyridine
Brain
Seizures
Bicuculline
Partial Epilepsy
Perfusion
Equipment and Supplies
Wounds and Injuries

Keywords

  • 4-Aminopyridine
  • Bicuculline
  • Cooling
  • Epileptiform discharge
  • Hippocampus
  • Magnesium free

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Neurology

Cite this

Motamedi, G. K., Salazar, P., Smith, E. L., Lesser, R. P., Webber, W. R. S., Ortinski, P. I., ... Rogawski, M. A. (2006). Termination of epileptiform activity by cooling in rat hippocampal slice epilepsy models. Epilepsy Research, 70(2-3), 200-210. https://doi.org/10.1016/j.eplepsyres.2006.05.001

Termination of epileptiform activity by cooling in rat hippocampal slice epilepsy models. / Motamedi, Gholam K.; Salazar, Patricia; Smith, Eric L.; Lesser, Ronald P.; Webber, William R S; Ortinski, Pavel I.; Vicini, Stefano; Rogawski, Michael A.

In: Epilepsy Research, Vol. 70, No. 2-3, 08.2006, p. 200-210.

Research output: Contribution to journalArticle

Motamedi, GK, Salazar, P, Smith, EL, Lesser, RP, Webber, WRS, Ortinski, PI, Vicini, S & Rogawski, MA 2006, 'Termination of epileptiform activity by cooling in rat hippocampal slice epilepsy models', Epilepsy Research, vol. 70, no. 2-3, pp. 200-210. https://doi.org/10.1016/j.eplepsyres.2006.05.001
Motamedi GK, Salazar P, Smith EL, Lesser RP, Webber WRS, Ortinski PI et al. Termination of epileptiform activity by cooling in rat hippocampal slice epilepsy models. Epilepsy Research. 2006 Aug;70(2-3):200-210. https://doi.org/10.1016/j.eplepsyres.2006.05.001
Motamedi, Gholam K. ; Salazar, Patricia ; Smith, Eric L. ; Lesser, Ronald P. ; Webber, William R S ; Ortinski, Pavel I. ; Vicini, Stefano ; Rogawski, Michael A. / Termination of epileptiform activity by cooling in rat hippocampal slice epilepsy models. In: Epilepsy Research. 2006 ; Vol. 70, No. 2-3. pp. 200-210.
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abstract = "Cooling has been shown to terminate experimentally induced epileptiform activity in models of epilepsy without causing injury to the cooled brain, suggesting that cooling could represent an approach to seizure control in intractable focal epilepsies. Here we sought to determine the most effective way to apply cooling to abort spontaneous epileptiform discharges in in vitro brain slice models. We induced spontaneous epileptiform activity in rat brain slices by exposure to 4-aminopyridine (4-AP), 4-AP plus bicuculline, and Mg2+-free artificial CSF (aCSF) at 28-34 °C. Extracellular field recordings were made at hippocampal or neocortical sites. Slice temperature was reduced by perfusion with cold aCSF. Rapid cooling at rates of 2-5 °C/s was compared to cooling at slower rates of 0.1-1 °C/s. Cooling at both rates reversibly aborted epileptiform discharges in all three models and at all recording sites. With rapid cooling, small temperature drops were highly effective in terminating discharges, an effect that was sustained for as long as the reduced temperature level was maintained. In contrast, slow cooling required much larger temperature drops to inhibit discharges. With slow cooling, absolute temperature drops to 21-22 °C caused a 90{\%} reduction in event frequency, but cooling to 14-15 °C was required to terminate discharges. We conclude that rapid cooling as effectively aborts discharges in in vitro epilepsy models as does slow cooling, but the magnitude of the temperature change required is less. Practical devices to inhibit seizure activity may only need to induce small temperature drops, if the cooling can be applied sufficiently rapidly.",
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