Tauchi Miyuki, Tejada de Rink Maria Mercedes, Fujioka Hiroshi, Okayama Satoko, Nakamura Kei-Ichiro, Dietel Barbara, Achenbach Stephan, Kollmar Rainer, Schwab Stefan, Ushijima Kazuo, Harada Hideki
Department of Neurology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Department of Molecular Neurology, and Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Ther Hypothermia Temp Manag. 2018 Dec;8(4):225-233. doi: 10.1089/ther.2017.0055. Epub 2018 Sep 8.
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.
目标温度管理（TTM），即治疗性低温，是缺血性和创伤性脑损伤后最有效的神经保护方法之一。TTM已通过多种方法应用于临床，但有效实现并维持目标温度仍具有挑战性。此外，为优化神经保护效果并将副作用降至最低，降温时机以及目标体温和脑温尚未标准化。局灶性脑冷却作为一种潜在策略，可减少全身TTM的不良反应。在本研究中，我们报告了一种用于动物的局灶性脑冷却装置及其在几种缺血性脑卒中动物模型中的局灶性冷却效果。使用珀耳帖元件（一种热电热泵）构建了局灶性脑冷却装置。该装置的冷却能力经过验证，并使用雄性Sprague-Dawley大鼠确定了诱导有效颅内温度的最佳设置。通过实验诱导短暂性和永久性大脑中动脉闭塞，并使用该装置在不同的冷却时机和持续时间下进行局灶性脑冷却。从尼氏染色的冷冻切片评估中风诱导的梗死体积和水肿体积。局灶性脑冷却装置能够在自由活动的大鼠中降低并随后维持脑低温，而不改变核心体温。经验证的颅内温度装置在缺血性神经死亡、再灌注损伤、半暗带进展性损伤和水肿形成的急性期产生了神经保护作用。总之，我们经过验证的局灶性冷却装置能够在大鼠中实现快速准确的脑TTM。使用该装置，我们能够在脑缺血的几个病理阶段测试局灶性TTM的神经保护作用，这为进一步研究开发针对脑卒中患者临床可行的TTM程序提供了依据。
