Behavioral Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD USA.
Oxid Med Cell Longev. 2010 Sep-Oct;3(5):332-41. doi: 10.4161/oxim.3.5.13184. Epub 2010 Sep 1.
In this study, we examined changes in central (anterior-preoptic hypothalamus) and peripheral (temporal muscle and facial skin) temperatures in freely moving rats following intravenous administration of bacterial lipopolysaccharides (LPS) at low doses (1 and 10 μg/kg) at thermoneutral conditions (28°C). Recordings were made with high temporal resolution (5-s bin) and the effects of LPS were compared with those induced by a tail-pinch, a standard arousing somato-sensory stimulus. At each dose, LPS moderately elevated brain, muscle, and skin temperatures. In contrast to rapid, monophasic and relatively short hyperthermic responses induced by a tail-pinch, LPS-induced increases in brain and muscle temperatures occurred with ~40 min onset latencies, showed three not clearly defined phases, were slightly larger with the 10 μm/kg dose, and maintained for the entire 4-hour post-injection recording duration. Based on dynamics of brain-muscle and skin-muscle temperature differentials, it appears that the hyperthermic response induced by LPS at the lowest dose originates from enhanced peripheral heat production, with no evidence of brain metabolic activation and skin vasoconstriction. While peripheral heat production also appears to determine the first phase of brain and body temperature elevation with LPS at 10 μg/kg, a further prolonged increase in brain-muscle differentials (onset at ~100 min) suggests metabolic brain activation as a factor contributing to brain and body hyperthermia. At this dose, skin temperature increase was weaker than in temporal muscle, suggesting vasoconstriction as another contributor to brain/body hyperthermia. Therefore, although both LPS at low doses and salient sensory stimuli moderately increase brain and body temperatures, these hyperthermic responses have important qualitative differences, reflecting unique underlying mechanisms.
在这项研究中,我们在常温(28°C)条件下,观察了低剂量(1 和 10μg/kg)静脉注射细菌脂多糖(LPS)后,自由活动大鼠的中枢(前下丘脑视前区)和外周(颞肌和面部皮肤)温度的变化。记录具有高时间分辨率(5 秒-bin),并将 LPS 的作用与尾巴夹引起的作用进行了比较,尾巴夹是一种标准的唤醒躯体感觉刺激。在每个剂量下,LPS 都适度升高了大脑、肌肉和皮肤的温度。与尾巴夹引起的快速、单相和相对短暂的高热反应不同,LPS 引起的大脑和肌肉温度升高的潜伏期约为 40 分钟,表现出三个不明确的阶段,用 10μg/kg 剂量略大,并且在整个 4 小时注射后记录持续时间内保持不变。基于大脑-肌肉和皮肤-肌肉温度差异的动力学,似乎用最低剂量 LPS 诱导的高热反应源自增强的外周产热,没有大脑代谢激活和皮肤血管收缩的证据。虽然外周产热似乎也决定了 LPS 引起的大脑和体温升高的第一阶段,但在 10μg/kg 时,大脑-肌肉差异的进一步延长增加(约 100 分钟时开始)表明代谢性大脑激活是导致大脑和身体高热的因素之一。在这个剂量下,皮肤温度的升高弱于颞肌,表明血管收缩是大脑/身体高热的另一个原因。因此,尽管低剂量 LPS 和显著的感觉刺激都适度地增加了大脑和体温,但这些高热反应具有重要的定性差异,反映了独特的潜在机制。