Targeted Temperature Management: Peltier's Element-Based Focal Brain Cooling Protects Penumbra Neurons from Progressive Damage in Experimental Cerebral Ischemia.

ABSTRACT

Targeted temperature management (TTM), or therapeutic hypothermia, is one of the most potent neuroprotective approaches after ischemic and traumatic brain injuries. TTM has been applied clinically with various methods, but effective achievement and maintenance of the target temperature remain challenging. Furthermore, timing of cooling and target body and brain temperature to optimize effectiveness for neuroprotection and to minimize side effects are yet to be standardized. Focal brain cooling is a potential strategy to minimize adverse effects of systemic TTM. In this study, we report on a focal brain cooling device for animals and its effectiveness of focal cooling in several animal models of ischemic cerebral stroke. A focal brain cooling device was constructed using a Peltier's element, a thermoelectric heat pump. The device was validated for its cooling ability, and optimal settings to induce an effective intracranial temperature were determined using male Sprague-Dawley rats. Transient and permanent middle cerebral artery occlusions were experimentally induced, and focal brain cooling was applied using the device varying the timing and duration of cooling. The stroke-induced infarct and edema volumes were evaluated from Nissl-stained cryosections. The focal brain cooling device was able to decrease and subsequently maintained cerebral hypothermia in free-moving rats without altering the core temperature. The device with validated intracranial temperatures produced neuroprotective effects in the acute phase of ischemic neural death, reperfusion injury, progressing damage to the penumbra, and edema formation. In conclusion, our validated focal cooling device enabled rapid and accurate cerebral TTM in rats. Using this device, we were able to test the neuroprotective effect of focal TTM in several pathological stages of cerebral ischemia, which warrants further studies to develop clinically feasible TTM procedures for patients with cerebral stroke.