Abstracts

Rationale: Our group and other researchers have demonstrated that focal brain cooling (FBC) terminates epileptic discharges (EDs). However, an analysis of the electroencephalogram (EEG) power spectrum during FBC has not yet been precisely performed. The aim of this study was therefore to investigate any changes in the frequency spectrum of EEGs due to cooling in a cortical seizure model. Methods: Male Sprague-Dawley rats (body weight 500-600 g) were anesthetized with urethane (1.25 g/kg, i.p.) and immobilized on a stereotactic frame. Following the application of 1% lidocaine to the skin, the left fronto-parietal skull was exposed, and a craniotomy (4x10 mm) was made over the sensorimotor cortex. A cooling device composed of a Peltier chip (4x4 mm) and heat sink was set on the dura-arachnoid. A thermocouple and an electrode for EEG recording were placed between the cooling device and the dura-arachnoid. To provoke EDs, penicillin G (PG, 400 U/ l) was administered into the sensorimotor cortex with a micro infusion pump for 5 minutes at a rate of 5 l/min (injection point; stereotactic coordinates relative to the bregma were 1 mm posterior and 3 mm lateral). EEGs were then continuously recorded after PG injection. After confirming the spontaneous recording of EDs, the cortex was cooled at temperatures of 25 C, 20 C, and 15 C for 5 minutes (n=5 in each group). The conditions for EEG recording were as follows: time constant, 0.3 second; high-frequency filter, 10 kHz; notch filter, on; reference electrode, neck muscle. A frequency analysis of the obtained EEG data was performed with a Fast Fourier Transform (FFT) and a power spectrum in each EEG frequency band (Delta: 1-4 Hz, Theta: 4-9 Hz, Alpha: 9-14Hz, Beta 1: 14-24Hz, and Beta 2: 24-30 Hz) was calculated before and during cooling. Results: Slower frequency bands (below 9 Hz) were predominant during pre-treatment, while faster frequency bands (alpha and beta range: 9-30 Hz) were found to increase after PG injection. Cooling the cortex at 25 C terminated the EEG power in the beta band (pre, 0.033 0.009; cooling, 0.011 0.006, p<0.05), cooling at 20 C suppressed both the alpha (pre, 0.059 0.001; cooling, 0.013 0.006, p<0.05) and beta bands (pre, 0.028 0.004; cooling, 0.004 0.002, p<0.05), and cooling at 15 C suppressed the EEG power in every frequency band (Figure, p<0.05).Conclusions: These results suggest that the EDs that propagate through the shallow layer (layer 2/3) of the cortex were selectively suppressed by FBC at 25 and 20 C. Furthermore, FBC at 15 C likely suppressed both the EDs and the cortical electrical activity in the deeper cortical layers. This work is therefore considered to positively contributes to the development of a novel treatment using FBC for patients with intractable neocortical epilepsy.