Elmquist J K, Scammell T E, Jacobson C D, Saper C B
Department of Neurology, Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts 02115, USA.
J Comp Neurol. 1996 Jul 15;371(1):85-103. doi: 10.1002/(SICI)1096-9861(19960715)371:1<85::AID-CNE5>3.0.CO;2-H.
The central nervous system, particularly the hypothalamus, is intimately involved in the coordination of various aspects of the inflammatory response, including the generation of fever. We used intravenous injections of bacterial cell wall lipopolysaccharide (LPS; 5 or 125 micrograms/kg) to stimulate the acute phase response and mapped the resultant distribution of Fos-like immunoreactivity in the rat brain. In addition, we compared the patterns of Fos distribution with the thermoregulatory responses elicited by the LPS. Administration of LPS resulted in a dose- and time-dependent pattern of Fos-like immunoreactivity throughout the rat brain consistent with a coordinated autonomic, endocrine, and behavioral response to the LPS challenge that was most pronounced 2 hours following injection. Specifically, Fos-like immunoreactivity was observed in key autonomic regulatory nuclear groups, including the insular and prelimbic cortices, paraventricular hypothalamic nucleus, parabrachial nucleus, nucleus of the solitary tract, and the rostral and caudal levels of the ventrolateral medulla. In addition, a significant sustained elevation of Fos-like immunoreactivity was observed in a cell group adjacent to the organum vasculosum of the lamina terminalis, which we termed the ventromedial preoptic area. This sustained elevation of Fos-like immunoreactivity coupled with the alterations in body temperature elicited by LPS leads us to hypothesize that the ventromedial preoptic area may be a key site for the initiation of fever during endotoxemia.
中枢神经系统，尤其是下丘脑，密切参与炎症反应各个方面的协调，包括发热的产生。我们通过静脉注射细菌细胞壁脂多糖（LPS；5或125微克/千克）来刺激急性期反应，并绘制了大鼠脑中由此产生的Fos样免疫反应性分布。此外，我们将Fos分布模式与LPS引发的体温调节反应进行了比较。LPS给药导致大鼠全脑Fos样免疫反应性呈剂量和时间依赖性模式，这与对LPS刺激的自主神经、内分泌和行为协调反应一致，在注射后2小时最为明显。具体而言，在关键的自主神经调节核团中观察到Fos样免疫反应性，包括岛叶和前边缘皮质、室旁下丘脑核、臂旁核、孤束核以及延髓腹外侧的头端和尾端水平。此外，在终板血管器相邻的一个细胞群中观察到Fos样免疫反应性显著持续升高，我们将其称为腹内侧视前区。Fos样免疫反应性的这种持续升高以及LPS引起的体温变化使我们推测，腹内侧视前区可能是内毒素血症期间发热起始的关键部位。
