Abstracts

Rationale: To explore the threshold temperature of rapid cooling required to terminate focal neocortical seizures in non-human primates. To investigate the mechanism of terminating seizures by cooling. Methods: All experiments were carried out on two eight year-old male cynomolgus monkies(Macaca fascicularis). A 20x30 mm cranial window was made over the left hemisphere above the motor cortex. The cortex was cooled with a15 mm diameter annular thermoelectric device (Peltier device) glued to the end of a custom machined copper bar designed to fit into the micromanipulator. The cooper bar also served as an efficient heat sink. A cortical electrode, a neurotransmitter probe, and a microinjector needle were inserted to 3 mm under the cortex through the central pore of the Peltier device. Seizures were induced by injecting 30 l artificial cerebrospinal fluid containing 25 mM 4-aminopyridine (4-AP) in the left lateral premotor cortex. At seizure onset, we used the Peltier device to cool the exposed cortical surface to 16-20C for 60 seconds and simultaneously used the FAST 16mklll system to determine the glutamate concentration in the cortex at different temperatures. Results: Within 5 minutes of 4-AP injection, animals developed recurrent seizures (average seizure duration 81.714.2s; average interictal period 66.932.9s; n=2) that persisted for 3 hours. When the Peltier device was used to cool the exposed cortical surface to 20C and 18C, there was no significant change in the duration or interval of seizures. When the temperature was reduced to 16C, the duration of seizures was significantly shortened to 50.54.9s (P < 0.05), the interval increased to 109.368.2s, and the glutamate concentration in the cortex decreased from 153.4M to 121.9M. Conclusions: At the threshold temperature of 16?, focal rapid cooling can successsfully reduce non-human primate neocortical seizures. At the same time, it can decrease the concentration of glutamate in the cortex, which may be one of the mechanisms that focal rapid cooling terminates seizures. Funding: National Science Foundation (81471391), Beijing Institute for Brain Disorders Foundation (BIBDPXM2014_014226_000016) .