Forensic Neuropathology of Hyperthermia

中暑定义为核心体温升高至40.6 ℃以上，并伴有精神状态异常，如因暴露于环境高温而导致的谵妄、惊厥或昏迷。乙醇摄入是中暑的一个诱发因素，这是一个相当广泛的共识。本研究采用小鼠高温模型，在预先给予乙醇和不给予乙醇的情况下，鉴定中暑引起的脑变化。将小鼠暴露于40 ℃的高温下，直至核心温度达到42 ℃，然后暴露于37 ℃ 15 min，可引起代谢性酸中毒和呼吸性酸中毒。高温小鼠大脑的免疫组织化学显示，在中央杏仁核（CeA），这是参与体温调节的c-fos免疫反应神经元的数量增加，作为神经元激活的标志。在热暴露、诱导性低血压、严重代谢性酸中毒和呼吸衰竭后，预先给予乙醇可维持较高的核心温度，从而产生中暑，并进一步增加小鼠CeA中c-fos免疫反应阳性神经元的数量。这些结果表明，高热与CeA中的神经元激活相关，并且由于乙醇的存在而加剧，从而暗示了中暑病因学中脑功能障碍的病理生理学和机制。

Heatstroke is defined as a core body temperature that rises above 40.6 ℃ and is accompanied by mental status abnormalities such as delirium, convulsions or coma resulting from exposure to environmental heat. There is fairly wide agreement that ethanol intake is a predisposing factor in heatstroke. This study was performed to identify the brain changes induced by heatstroke, using a mouse hyperthermia model with and without preceding ethanol administration. Exposure to heat of 40 ℃ until the core temperature reached to 42 ℃ followed by exposure to 37 ℃ for 15 min induced metabolic acidosis and respiratory alkalosis in mice. Immunohistochemistry of the brains of hyperthermia mice showed an increase in the number of c-fos immunoreactive neurons, as a marker of neuronal activation, in the central amygdaloid nucleus (CeA), which is involved in thermoregulation. Preceding ethanol administration maintained a high core temperature after heat exposure, induced hypotension, severe metabolic acidosis and respiratory failure, and accordingly, produced heatstroke, and further increased the number of c-fos immunoreactive neurons in the CeA in mice. These results indicate that hyperthermia is associated with neuronal activation in the CeA and is exacerbated by the presence of ethanol, implicating the pathophysiology and mechanisms of brain dysfunctions in the etiology of heatstroke.