González-Hernández T, Rustioni A
Department of Cell Biology and Anatomy, School of Medicine, The University of North Carolina at Chapel Hill, USA.
J Neurosci Res. 1999 Jan 15;55(2):198-207. doi: 10.1002/(SICI)1097-4547(19990115)55:2<198::AID-JNR7>3.0.CO;2-M.
Nitric oxide (NO) is a short-lived molecule with messenger and cytotoxic functions in nervous, cardiovascular, and immune systems. Nitric oxide synthase (NOS), the enzyme responsible for NO synthesis, exists in three different forms: the neuronal (nNOS), present in discrete neuronal populations; the endothelial (eNOS), present in vascular endotheliun, and the inducible isoform (iNOS), expressed in various cell types when activated, including macrophages and glial cells. In this study, we have investigated the possible involvement of NO in Wallerian degeneration and the subsequent regeneration occurring after sciatic nerve ligature, using histochemistry and immunocytochemistry for the three NOS isoforms, at different postinjury periods. Two days after lesion, the three NOS isoforms are overexpressed, reaching their greatest expression during the second week. nNOS is upregulated in dorsal root ganglion neurons, centrifugally transported and accumulated in growing axons. eNOS is overexpressed in vasa nervorum of the distal stump and around ligature, and iNOS is induced in recruited macrophages. These findings indicate that different cellular sources contribute to maintain high levels of NO at the lesion site. The parallelism between NOS inductions and well-known repair phenomena suggests that NO, acting in different ways, may exert a beneficial effect on nerve regeneration.
一氧化氮（NO）是一种半衰期较短的分子，在神经、心血管和免疫系统中具有信使和细胞毒性功能。一氧化氮合酶（NOS）是负责合成NO的酶，以三种不同形式存在：神经元型（nNOS），存在于离散的神经元群体中；内皮型（eNOS），存在于血管内皮中；诱导型异构体（iNOS），在激活时在包括巨噬细胞和神经胶质细胞在内的各种细胞类型中表达。在本研究中，我们使用针对三种NOS异构体的组织化学和免疫细胞化学方法，在不同的损伤后时期，研究了NO在坐骨神经结扎后发生的沃勒变性和随后的再生过程中可能的参与情况。损伤后两天，三种NOS异构体均过度表达，在第二周达到最大表达水平。nNOS在背根神经节神经元中上调，经离心运输并积聚在生长的轴突中。eNOS在远端残端的神经血管和结扎周围过度表达，iNOS在募集的巨噬细胞中被诱导。这些发现表明不同的细胞来源有助于在损伤部位维持高水平的NO。NOS诱导与众所周知的修复现象之间的平行关系表明，以不同方式起作用的NO可能对神经再生产生有益影响。
