Effective suppression of hippocampal seizures in rats by direct hippocampal cooling with a Peltier chip

Laboratory investigation

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Object

The use of focal brain cooling to eliminate epileptic discharges (EDs) has attracted increasing attention in the scientific community. In this study, the inhibitory effect of selective hippocampal cooling on experimental hippocampal seizures was investigated using a newly devised cooling system with a thermoelectric (Peltier) chip.

Methods

A copper needle coated with silicone and attached to the Peltier chip was used for the cooling device. The experiments were performed first in a phantom model with thermography and second in adult male Sprague–Dawley rats in a state of halothane anesthesia. The cooling needle, a thermocouple, and a needle electrode for electroencephalography recording were inserted into the right hippocampus. Kainic acid (KA) was injected into the right hippocampus to provoke the EDs. The animals were divided into hippocampal cooling (10 rats) and noncooling (control, 10 rats) groups.

Results

In the phantom study, the cooling effects (9°C) occurred in the spherical areas around the needle tip. In the rats the temperature of the cooled hippocampus decreased below 20°C within a 1.6-mm radius and below 25°C within a 2.4-mm radius from the cooling center. The temperature at the needle tip decreased below 20°C within 1 minute and was maintained at the same level until the end of the cooling process. The amplitude of the EDs was suppressed to 68.1 ± 4.8% of the precooling value and remained low thereafter. No histological damage due to cooling was observed in the rat hippocampus.

Conclusions

Selective hippocampal cooling effectively suppresses the KA-induced hippocampal EDs. Direct hippocampal cooling with a permanently implantable system is potentially useful as a minimally invasive therapy for temporal lobe epilepsy and therefore could be an alternative to the temporal lobectomy.

Abbreviations used in this paper: ED = epileptic discharge; EEG = electroencephalography; KA = kainic acid; RMS = root mean square; TLE = temporal lobe epilepsy.

Article Information

Address correspondence to: Masami Fujii, M.D., Ph.D., Department of Neurosurgery, Yamaguchi University School of Medicine, 1-1-1, Minami-kogushi, Ube, Yamaguchi 755-8505, Japan. email: masfujii@yamaguchi-u.ac.jp.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Diagram depicting the cooling device. When the electric current is passed between the conductors of the Peltier chip, 1 side is cooled and the other is heated. The heat sink was attached to the heated side of the chip. The cooling needle and plate made of copper were attached to the Peltier chip on the cooled side. The needle was coated with the silicone except for its tip.

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    Left: Photograph showing the cooling needle being inserted into the agar. Right: Thermogram demonstrating the cooling needle (in agar) when 1 A of electric current was passed through the Peltier chip.

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    Diagram demonstrating the locations of the cooling device, electrode for EEG recording, and microinjection needle for the KA injection. The tip of the copper needle was located within the hippocampus.

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    Diagram showing the temperature distribution in the rat hippocampus. The temperature reached below 20°C within a 1.6-mm radius and below 25°C within a 2.4-mm radius from the cooling center.

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    Tracings depicting typical examples of the EEG recordings obtained in the cooling group animals before and after cooling.

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    Graphs showing typical examples of the changes in the amplitude and RMSs of the epileptiform discharges and the temperatures at the needle tip in the cooling group animals before and after cooling.

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    Graphs depicting sequential changes in the temperature and amplitude of the EDs before and after cooling. Black circles represent the control group (10 rats); black squares, the cooling group (10 rats); and black triangles, mean temperatures in the cooling group. *p < 0.05.

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    Photomicrographs of H & E–stained coronal hippocampal sections obtained in a representative cooling group animal (left) and a control (right), demonstrating no apparent difference. Bar = 1 μm.

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