The influence of focal brain cooling on neurophysiopathology: validation for clinical application

Abstract

Object Focal brain cooling has been recognized to have a suppressive effect on epileptiform discharges or a protective effect on brain tissue. However, the precise influence of brain cooling on normal brain function and histology has not yet been thoroughly investigated. The aim of this study was to investigate the neurophysiopathological consequences of focal cooling and to detect the threshold temperature that causes irreversible histological change and motor dysfunction. Methods The experiments were performed in adult male Sprague-Dawley rats (weighing 250–350 g) after induction of halothane anesthesia. A thermoelectric chip (6 × 6 × 2 mm) was used as a cooling device and was placed on the surface of the sensorimotor cortex after a 10 × 8–mm craniotomy. A thermocouple was placed between the chip and the brain surface. Focal cooling of the cortex was performed at the temperatures of 20, 15, 10, 5, 0, and −5°C for 1 hour (5 rats in each group). Thereafter, the cranial window was repaired. Motor function was evaluated using the beam-walking scale (BWS) every day for 7 days. The rats were killed 7 days after the operation for histological examination with H & E, Klüver-Barrera, glial fibrillary acidic protein, and terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate nick-end labeling stainings. The authors also euthanized some rats 24 hours after cooling and obtained brain sections by the same methods. Results The BWS score was decreased on the day after cooling only in the −5°C group (p < 0.05), whereas the score did not change in the other temperature groups. Histologically, the appearance of cryoinjury such as necrosis, apoptosis, loss of neurons, and marked proliferation of astrocytes at the periphery of the lesion was observed only in the −5°C group, while no apparent changes were observed in the other temperature groups. Conclusions The present study confirmed that the focal cooling of the cortex for 1 hour above the temperature of 0°C did not induce any irreversible histological change or motor dysfunction. These results suggest that focal brain cooling above 0°C has the potential to be a minimally invasive and valuable modality for the treatment of severe brain injury or to assist in the examination of brain function.