Scott D E, Wu W, Slusser J, Depto A, Hansen S
Department of Anatomy and Neurobiology, Eastern Virginia Medical School, Norfolk 23501.
Exp Neurol. 1995 Jan;131(1):23-38. doi: 10.1016/0014-4886(95)90004-7.
Central to this investigation are several basic hypotheses that are designed to test the role of nitric oxide (NO) in the complex process of central regeneration and plasticity in a well established model system of the mammalian brain. We have employed histochemical techniques at the light and ultrastructural level coupled with correlative scanning electron microscopy, immunoelectron microscopy, and in situ hybridization in order to determine the functional significance of the increased expression of nitric oxide synthase (NOS) in neurons of the supraoptic (SON) and paraventricular (PVN) nuclei which accompanies regeneration of their axotomized neurites following hypophysectomy. The aim of this investigation was to determine the potential role and temporal up-regulation of NOS in this basic regenerative process and to establish the ultrastructural and neuroanatomical correlates during critical periods of regeneration and regrowth of SON and PVN axons following hypophysectomy in the endocrine hypothalamus of the rat. Our data support the hypothesis that NO may serve as a second messenger molecule that may act in some fashion to govern not only the process of central regeneration and regrowth of magnocellular (SON/PVN) axons into the median eminence, neural stem, and neural lobe (the neurohypophyseal system) but may also influence the regeneration of neurites into new neuroanatomical domains such as the adjacent lumen of the third cerebral ventricle. We have demonstrated a distinct temporal relationship between injury (axotomy) of SON/PVN axons and the establishment of new neurovascular zones following hypophysectomy with the up-regulation of NOS. This up-regulation appears to correlate well with successful regeneration in the mammalian neurohypophyseal system. We have also successfully inhibited axonal regeneration with the use of nitroarginine, a competitive antagonist of NO. NOS up-regulation attendant to regeneration of SON and PVN axons may have inestimable clinical implications, particularly with respect to closed head injury and cerebral contusion that involves the mechanical shearing of the infundibular stalk. In addition, this investigation has reaffirmed that large numbers of bona fide neurons migrate and emerge upon the floor of the adjacent third cerebral ventricle shortly following hypophysectomy (within 2 weeks). The origin and mechanisms of neuronal migration and plasticity following hypophysectomy are the subject of interpretation and discussion in this investigation.
本研究的核心是几个基本假设，这些假设旨在在一个成熟的哺乳动物脑模型系统中，测试一氧化氮（NO）在中枢再生和可塑性这一复杂过程中的作用。我们运用了光镜和超微结构水平的组织化学技术，结合相关的扫描电子显微镜、免疫电子显微镜和原位杂交技术，以确定视上核（SON）和室旁核（PVN）神经元中一氧化氮合酶（NOS）表达增加的功能意义，这种增加伴随着垂体切除术后其轴突切断的神经突的再生。本研究的目的是确定NOS在这个基本再生过程中的潜在作用和时间上调，并在大鼠内分泌下丘脑垂体切除术后SON和PVN轴突再生和再生长的关键时期建立超微结构和神经解剖学相关性。我们的数据支持这样的假设，即NO可能作为一种第二信使分子，可能以某种方式发挥作用，不仅控制大细胞（SON/PVN）轴突向正中隆起、神经干和神经叶（神经垂体系统）的中枢再生和再生长过程，而且还可能影响神经突向新的神经解剖学区域的再生，如第三脑室相邻的管腔。我们已经证明，SON/PVN轴突损伤（轴突切断）与垂体切除术后新神经血管区的建立以及NOS的上调之间存在明显的时间关系。这种上调似乎与哺乳动物神经垂体系统中的成功再生密切相关。我们还成功地使用了NO的竞争性拮抗剂硝基精氨酸抑制了轴突再生。SON和PVN轴突再生伴随的NOS上调可能具有不可估量的临床意义，特别是对于涉及漏斗柄机械剪切的闭合性头部损伤和脑挫伤。此外，本研究再次证实，垂体切除术后不久（2周内），大量真正的神经元迁移并出现在相邻第三脑室的底部。垂体切除术后神经元迁移和可塑性的起源和机制是本研究解释和讨论的主题。
