Differential effects of rapid hypothermia on pyramidal neurons and interneurons in epileptogenic tissue of epileptic patients

Abstract

Objective To explore the different effects of rapid hypothermia on the electrophysiological characteristics of pyramidal neurons and interneurons in epileptic patients. Methods A total of 13 brain tissue samples were selected from patients with focal drug ⁃ resistant epilepsy who underwent epileptogenic lesion resection in Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University from June to December 2016. Using perfusion method, the brain tissue slice temperature was quickly reduced to 20 ℃ in a step manner, then rewarmed to 30 ℃, and maintained at 30 ℃ for 10 min (the target temperature was changed by 5 ℃ every 10 min). Patch clamping technique was used to record the resting membrane potential, synaptic activity and action potential of pyramidal neurons (n=18) and interneurons (n=6) in epileptic cerebral cortex. Results 1) Resting membrane potential: when the temperature dropped to 20 ℃, the resting membrane potential of the two kinds of neurons showed slight depolarization, but there was no statistical significance in the changes of resting membrane potential at different temperatures and the changes of resting membrane potential of the two kinds of neurons at the same temperature (P＞0.05, for all). 2) Synaptic activity: after cooling, the amplitude of excitatory postsynaptic current (EPSC) of interneuron was smaller (F=5.332, P=0.034). The normalized percentages of EPSC (F=8.811, P=0.000) and inhibitory postsynaptic current (IPSC; F=9.843, P=0.000) amplitude, EPSC event interval (F=7.065, P=0.001), EPSC (F=6.281, P=0.002) and IPSC (F=8.266, P=0.000) peak area were statistically significant. 3) Action potential: there were no significant differences in the effects of temperature change on the normalized percentages of the threshold, frequency, amplitude and half⁃width time of the action potential of the two kinds of neurons (P＞0.05, for all). However, the differences of normalized percentages of action potential frequency (F=4.801, P=0.008), amplitude (F=3.680, P=0.015) and half⁃width time (F=28.951, P=0.000) of neuronal action potentials at different temperatures were statistically significant. Conclusions When the temperature was reduced to 20 ℃, the electrophysiological activities of the two kinds of neurons were significantly inhibited. The inhibition of EPSC amplitude of synaptic activity in interneurons was stronger than that in pyramidal neurons. Inhibition of interneuron activity may be one of the reasons for hypothermia prevention and termination of epilepsy.

Keywords

• epilepsy
• hypothermia induced
• pyramidal cells
• interneurons
• electrophysiological phenomena