ANIMAL MODELS OF AUTONOMIC FAILURE

我们将研究两种大鼠自主神经障碍的实验模型： 1)成熟的节后交感神经切断术 (2)一种新的节前交感神经切除模型。 由乙酰胆碱酯酶抗体引起。这些模型将与 彼此之间，结果也将被用于评估 与纯自主神经衰竭(PAF)和多器官功能衰竭患者的对应关系 伴有自主神经衰竭的系统萎缩(MSA)。生物多样性的形态计量学研究 脊髓和交感神经节将用NADPH-黄递酶进行手术 组织化学和酪氨酸羟化酶免疫组织化学检测 节前和节后交感神经损伤的部位和严重程度 神经元。涉及心血管反应的药理学实验 直接和间接作用的药物将有助于描述 与人类比较的动物模型的病理生理学 对口单位。将研究儿茶酚胺的释放和代谢 集中进行血浆和尿样的高效液相色谱检测 休息，并在轻度制动后应激。静息和刺激水平 神经肽和选定的多肽激素也将被检查。我们 预计综合起来的结果将支持胍乙定的观点 交感神经切除是PAF的一个很好的模型，而抗体诱导的节前 交感神经切除术在其外周表现上类似于MSA。

We will investigate two experimental models of autonomic disorders in rats: 1) the well established postganglionic sympathectomy induced by guanethidine, and 2) a novel model of preganglionic sympathectomy induced by antibodies to acetylcholinesterase. These models will be compared with each other, the results will also be used to assess the degrees of correspondence to patients with pure autonomic failure (PAF) and multiple system atrophy with autonomic failure (MSA). Morphometric studies of the spinal cord and sympathetic ganglia will be performed with NADPH-diaphorase histochemistry and tyrosine hydroxylase immunohistochemistry to define the location and severity of losses of pre- and postganglionic sympathetic neurons. Pharmacologic experiments involving cardiovascular responses to direct and indirectly acting drugs will aid in characterizing the pathophysiology of the animal models for comparison with their human counterparts. Catecholamine release and metabolism will be studied intensively by HPLC determinations on plasma and urine samples obtained at rest and after mild immobilization stress. Resting and stimulated levels of neuropeptides and selected peptide hormones will also be examined. We expect the results taken together will support the view that guanethidine sympathectomy is a good model for PAF, while antibody-induced preganglionic sympathectomy, in its peripheral manifestations, is a close analog of MSA.