Hypothermia Terminates Epileptiform Discharges in an In Vitro Epilepsy Model.
Abstract number :
3.036
Submission category :
Year :
2001
Submission ID :
134
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
E.L. Smith, Epilepsy Research Branch, NINDS, NIH, Bethesda, MD; G.K. Motamedi, MD, NINDS, NIH/John Hopkins, Bethesda, MD; R.P. Lesser, MD, Neurology, John Hopkins, Baltimore, MD; M.A. Rogawski, MD,PhD, NINDS, NIH, Bethesda, MD
RATIONALE: The goal of this study was to determine if local cooling of an epileptogenic brain region can inhibit the expression of epileptiform activity.
METHODS: Spontaneous epileptiform discharges were induced in hippocampal slices from young Sprague-Dawley rats by perfusion with the convulsant potassium channel blocker 4-aminopyridine (4-AP; final concentration, 50-60 [mu]M). Extracellular field potential recordings were made from the CA3 and CA1 regions using glass micropipettes filled with 1 M NaCl. Field EPSPs were evoked in the CA3 region by stimulation of the perforant path. The temperature of the slice was controlled with a resistive heater in the recording chamber. Hypothermia was induced by perfusion with cooled bathing solution.
RESULTS: The effect of cooling was studied in five slices from separate rats. At normal recording temperatures (29[degree]-30[degree]C), all slices exhibited spontaneous epileptiform bursting in the CA1 and CA3 at a rate of 5-10Hz. After insuring that the baseline burst rate was stable, the temperature was gradually decreased to 24[degree]-25[degree]C over 3 to 6 min. This resulted in a 91 [plusminus] 7.8% decrease in the frequency of bursting. In addition, the bursts exhibited 58 [plusminus] 22.1% decrease in amplitude. The reduction in burst frequency and amplitude persisted as long as the hypothermia was maintained (up to 17 min), but partially resolved upon warming to the baseline temperature. On average, the recovery burst frequency and amplitude were 28.4 [plusminus] 15.8% and 76.1 [plusminus] 19.4% of the baseline values, respectively. In one experiment, the slice temperature was reduced more abruptly (over 30-60s). In this experiment, the burst frequency and amplitude recoverd less fully than with gradual cooling. With gradual cooling, the burst frequency and amplitude recovered to a maximum of 90% and 137%, respectively, even though burst activity was completely suppressed during the cooling. Evoked field responses were unchanged by hypothermia when epileptiform bursting was eliminated indicating that hypothermia does not produce nonspecific effects on synaptic transmission and neuronal excitability.
CONCLUSIONS: In the 4-AP in vitro hippocampal slice model, hypothermia attenuates or stops epileptiform discharges in a reversible manner without causing a generalized suppression of neuronal function. Local hypothermia might represent a treatment approach for refractory partial epilepsies.
Support: National Institutes of Health - National Institute of Neurological Disorders and Strokes