NOVEL APPROACH TO ANALYSIS OF MULTIPLE INSULTS TO PNS

周围神经系统可能会受到多种同时 侮辱。 这些包括创伤，炎症，疾病的影响， 糖尿病和药物，或者毒素。 相互作用很难研究 vivo. 在本建议中，我们将使用改进的等辐射线分析， 研究缺氧和苏拉明诱导的神经毒性之间的相互作用。 糖尿病神经病变的潜在机制之一是血管 导致神经缺氧或缺血的病理学。 苏拉明是一个 用于治疗实体瘤的实验性化疗剂 包括乳腺癌和前列腺癌。 剂量限制的一方 这种药物的作用是周围神经病变。 的机制 周围神经缺氧损伤 神经系统（PNS）尚未完全定义，双重作用 侮辱很难研究。 我们认为苏拉明和缺氧 两者都通过钙介导的途径产生神经损伤。 使用 原代背根神经节神经元作为体外模型系统，我们将 研究相互作用的机制并确定其是否具有协同作用 或添加剂。 如果存在相互作用，我们将检验以下假设： 会聚发生在钙信号传导水平。

The peripheral nervous system may be subjected to multiple simultaneous insults. These include trauma, inflammation, the effects of diseases such as diabetes and drugs, or toxins. Interactions are difficult to study in vivo. In this proposal, we will use modified isobolographic analysis to study the interaction between hypoxia- and suramin-induced neurotoxicity. One of the proposed mechanisms underlying diabetic neuropathy is vascular pathology resulting in neural hypoxia or ischemia. Suramin is an experimental chemotherapeutic agent used in the treatment of solid tumors including breast and prostate cancers. One of the dose-limiting side effects of this agent is peripheral neuropathy. The mechanisms of hypoxia- and antineoplastic agent-induced nerve injury in the peripheral nervous system (PNS) have not been fully defined and the effect of double insults has been difficult to study. We propose that suramin and hypoxia both produce nerve injury by way of calcium-mediated pathways. Using primary dorsal root ganglion neurons as an in vitro model system, we will study the mechanism of interaction and determine whether it is synergistic or additive. If there is interaction we will test the hypothesis that convergence occurs at the level of calcium signaling.