Xu M, Ng Y K, Leong S K
Department of Anatomy, Faculty of Medicine, The National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260, Singapore.
Brain Res. 1998 Oct 12;808(1):23-30. doi: 10.1016/s0006-8993(98)00787-2.
In the present study, immunohistochemical stainings for OX-6, OX-42, nitric oxide synthase I and II as well as nitrotyrosine were used to investigate possible correlation among microglial reactivity, nitric oxide synthase upregulation, peroxynitrite involvement and neuronal death in the nucleus dorsalis and red nucleus following lower thoracic spinal cord hemisection. Significant neuronal loss was found in the ipsilateral nucleus dorsalis and contralateral red nucleus after cord hemisection. A distinctive microglial reaction for OX-42 could be observed from one to four weeks post axotomy in the ipsilateral nucleus dorsalis; by contrast, it was observed on both sides of the red nucleus from one to three weeks following cord hemisection. The activated microglial cells showed some degree of hypertrophy. From the microglial immunoreactivity as well as their appearance, it was speculated that microglial activation might be beneficial or protective to the axotomized neurons. In normal and sham-operated rats, neurons of the nucleus dorsalis were not nitric oxide synthase I reactive. Three weeks after cord hemisection, neurons in the ipsilateral nucleus dorsalis below the lesion showed strong immunoreactivity. Neurons in the red nucleus that normally displayed weak nitric oxide synthase I immunoreactivity showed an increase on both sides of the nucleus. These results suggested that nitric oxide synthase I expression in the nucleus dorsalis following axotomy was synthesized de novo and might act as a neurotoxic agent. However, the bilateral increase in expression of nitric oxide synthase I in the red nucleus after lower thoracic cord hemisection was due to up-regulation of the constitutive enzyme and might have some neuroprotective function. Our results also suggested that peroxynitrite played no or little role in the neurodegeneration in the nucleus dorsalis and red nucleus following axotomy.
在本研究中，采用针对OX - 6、OX - 42、一氧化氮合酶I和II以及硝基酪氨酸的免疫组织化学染色，来研究胸段脊髓半横断后背核和红核中，小胶质细胞反应性、一氧化氮合酶上调、过氧亚硝酸盐参与情况与神经元死亡之间的可能相关性。脊髓半横断后，在同侧背核和对侧红核中发现了显著的神经元丢失。在同侧背核，轴突切断后1至4周可观察到针对OX - 42的独特小胶质细胞反应；相比之下，脊髓半横断后1至3周，在红核两侧均观察到这种反应。活化的小胶质细胞呈现出一定程度的肥大。从小胶质细胞免疫反应性及其外观推测，小胶质细胞活化可能对轴突切断的神经元有益或具有保护作用。在正常和假手术大鼠中，背核神经元对一氧化氮合酶I无反应性。脊髓半横断3周后，损伤下方同侧背核中的神经元显示出强烈的免疫反应性。正常情况下一氧化氮合酶I免疫反应性较弱的红核神经元，在两侧核中均出现增加。这些结果表明，轴突切断后背核中一氧化氮合酶I的表达是重新合成的，可能作为一种神经毒性剂起作用。然而，胸段脊髓半横断后红核中一氧化氮合酶I表达的双侧增加是由于组成型酶的上调，可能具有一定的神经保护功能。我们的结果还表明，过氧亚硝酸盐在轴突切断后背核和红核中的神经退行性变中作用不大或几乎不起作用。
