Department of Obstetrics and Gynecology, Chi Mei Medical Center, Tainan, Taiwan ; Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
Curr Neuropharmacol. 2013 Mar;11(2):129-40. doi: 10.2174/1570159X11311020001.
The hypothalamus may be involved in regulating homeostasis, motivation, and emotional behavior by controlling autonomic and endocrine activity. The hypothalamus communicates input from the thalamus to the pituitary gland, reticular activating substance, limbic system, and neocortex. This allows the output of pituitary hormones to respond to changes in autonomic nervous system activity. Environmental heat stress increases cutaneous blood flow and metabolism, and progressively decreases splanchnic blood flow. Severe heat exposure also decreases mean arterial pressure (MAP), increases intracranial pressure (ICP), and decreases cerebral perfusion pressure (CPP = MAP - ICP), all of which lead to cerebral ischemia and hypoxia. Compared with normothermic controls, rodents with heatstroke have higher hypothalamic values of cellular ischemia (e.g., glutamate and lactate-to-pyruvate ratio) and damage (e.g., glycerol) markers, pro-oxidant enzymes (e.g., lipid peroxidation and glutathione oxidation), proinflammatory cytokines (e.g., interleukin-1β and tumor necrosis factor-α), inducible nitric oxide synthase-dependent nitric oxide, and an indicator for the accumulation of polymorphonuclear leukocytes (e.g., myeloperoxidase activity), as well as neuronal damage (e.g., apoptosis, necrosis, and autophagy) after heatstroke. Hypothalamic values of antioxidant defenses (e.g., glutathione peroxidase and glutathione reductase), however, are lower. The ischemic, hypoxic, and oxidative damage to the hypothalamus during heatstroke may cause multiple organ dysfunction or failure through hypothalamic-pituitary-adrenal axis mechanisms. Finding the link between the signaling and heatstroke-induced hypothalamic oxidative and ischemic damage might allow us to clinically attenuate heatstroke. In particular, free radical scavengers, heat shock protein-70 inducers, hypervolemic hemodilution, inducible nitric oxide synthase inhibitors, progenitor stem cells, flutamide, estrogen, interleukin-1 receptor antagonists, glucocorticoid, activated protein C, and baicalin mitigate preclinical heatstroke levels.
下丘脑可能通过控制自主神经和内分泌活动来调节体内平衡、动机和情绪行为。下丘脑将来自丘脑的输入传递到垂体、网状激活物质、边缘系统和新皮质。这使得垂体激素的输出能够响应自主神经系统活动的变化。环境热应激会增加皮肤血流量和新陈代谢，逐渐减少内脏血流量。严重的热暴露还会降低平均动脉压（MAP）、增加颅内压（ICP）和降低脑灌注压（CPP = MAP - ICP），所有这些都会导致脑缺血和缺氧。与正常体温对照相比，中暑的啮齿动物下丘脑细胞缺血（如谷氨酸和乳酸/丙酮酸比值）和损伤（如甘油）标志物、促氧化剂酶（如脂质过氧化和谷胱甘肽氧化）、促炎细胞因子（如白细胞介素-1β和肿瘤坏死因子-α）、诱导型一氧化氮合酶依赖性一氧化氮以及多形核白细胞积聚的标志物（如髓过氧化物酶活性）以及中暑后神经元损伤（如凋亡、坏死和自噬）的水平更高。然而，下丘脑抗氧化防御（如谷胱甘肽过氧化物酶和谷胱甘肽还原酶）的水平较低。中暑时下丘脑的缺血、缺氧和氧化损伤可能通过下丘脑-垂体-肾上腺轴机制导致多器官功能障碍或衰竭。找到信号转导与中暑引起的下丘脑氧化和缺血损伤之间的联系，可能使我们能够在临床上减轻中暑的影响。特别是自由基清除剂、热休克蛋白-70 诱导剂、高容量血液稀释、诱导型一氧化氮合酶抑制剂、祖细胞干细胞、氟他胺、雌激素、白细胞介素-1 受体拮抗剂、糖皮质激素、激活蛋白 C 和黄芩苷可以减轻临床前中暑水平。
