ANIMAL MODELS OF AUTONOMIC FAILURE

我们将研究两种大鼠自主神经紊乱的实验模型： 1)已建立的节后交感神经切除术诱导的 乙啶，和2）一种新的模型，节前交感神经切除术诱导 乙酰胆碱酯酶的抗体。 这些模型将与 结果也将用于评估 与单纯自主神经功能衰竭（PAF）和多个 系统萎缩伴自主神经功能衰竭（MSA）。 的形态计量学研究 脊髓和交感神经节将用NADPH-黄递酶进行 组织化学和酪氨酸羟化酶免疫组织化学来确定 神经节前和节后交感神经功能丧失的部位和严重程度 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表征 动物模型的病理生理学，用于与人类进行比较 同行 将研究儿茶酚胺的释放和代谢 通过高效液相色谱法对在以下地点获得的血浆和尿液样本进行集中测定 休息和轻度制动应激后。 静息和刺激水平 神经肽和选定的肽激素也将进行检查。 我们 我希望这些结果能支持乙啶 交感神经切除术是PAF的良好模型，而抗体诱导的节前 交感神经切除术在其外周表现上与MSA相似。

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.