PATHOGENESIS OF TOXIC AND METABOLIC NEUROPATHIES

糖尿病的神经后果只影响 外周神经系统(PNS)和高代谢相关 山梨醇途径的活性与内源性微血管 具有长期结构性后果的变化。 高血糖是潜在的缺陷，因为神经 不依赖于胰岛素，过量的葡萄糖进入神经内膜 转化为具有渗透活性的多元醇。运输机制 它们通过血-神经屏障运送己糖也携带 钠进入神经内膜导致渗透性增加 活动与神经传导速度减慢和 代谢期早期神经纤维直径减小 哪种神经病变最适合用醛糖治疗？ 还原酶抑制剂和胰岛素。我们的研究重点是：1)联系 钠升高和电生理障碍之间的关系，II) 钠在轴突和轴突内的精细结构定位 结旁区域和III)糖原积累的机制 糖尿病轴突。在疾病的后期 微循环改变成为既定的，并产生影响 关于轴突变性和脱髓鞘的神经纤维 发生。微血管病变，导致毛细血管变窄， 是牵连的，拟议的研究特别重视 对经神经外膜微循环的意义 在神经内膜缺血的发病机制中起关键作用。两者都有 高血糖和低氧是其潜在的机制 对发病机制的贡献将单独进行调查。 使用新技术测量神经血流量， 神经内膜电解质的x射线微探头分析 氧分压和神经内液体压。生物物理 旨在调查神经内膜的干扰的技术 微环境将与经典的形态和 形态计量学方法确定早期牙周炎的发病机制 糖尿病神经病变患者对其发病方式的认识变化 在不可逆转之前启动适当的治疗至关重要 神经性变化太棒了。

The neurological consequences of diabetes exclusively affect the peripheral nervous system (PNS) and are linked to hypermetabolic activity in the sorbitol pathway and intrinsic microvascular changes which have long-term structural consequences. Hyperglycemia is the underlying defect and since nerves are insulin-independent, excess glucose enters the endoneurium being converted into osmotically active polyols. Transport mechanisms which convey hexoses across the blood-nerve barrier also carry sodium into the endoneurium resulting in increased osmotic activity associated with reduced nerve conduction velocity and reduced nerve fiber diameter in the early metabolic phase, during which neuropathy is most amenable to treatment with aldose reductase inhibitors and insulin. Our studies focus i) on the link between increased sodium and electrophysiologic disturbances, ii) fine structural localization of increased sodium in the axon and paranodal region and iii) mechanisms of glycogen accumulation in diabetic axons. In the latter stages of the disease microcirculatory changes become established and have an impact on the nerve fiber in which axonal degeneration and demyelination occur. Microangiopathy, resulting in narrowing of the capillaries, is implicated and the proposed research attaches particular significance to the transperineurial microcirculation which may play a key role in the pathogenesis of endoneurial ischemia. Both hyperglycemia and hypoxia are underlying mechanisms whose contributions to pathogenesis will be individually investigated using new techniques for measurement of nerve blood flow, endoneurial electrolyte analysis by x-ray microprobe, nerve oxygen tension and endoneurial fluid pressure. Biophysical techniques designed to investigate disturbances in the endoneurial microenvironment will be combined with classic morphologic and morphometric methods to determine the pathogenesis of the early changes in diabetic neuropathy knowledge of whose onset is crucial to initiate appropriate treatment before irreversible neuropathic changes supervene.