Muldoon L L, Varallyay P, Kraemer D F, Kiwic G, Pinkston K, Walker-Rosenfeld S L, Neuwelt E A
Department of Neurology, Division of Medical Informatics and Outcomes Research, Oregon Health and Science University, OR 97239, USA.
Neuropathol Appl Neurobiol. 2004 Feb;30(1):70-9. doi: 10.1046/j.0305-1846.2003.00512.x.
Central nervous system (CNS) drainage may occur via connections to the vasculature, but in animal models up to 50% occurs via perivascular, perineural and primitive lymphatic drainage to cervical lymph nodes. We evaluated efflux of particles from the brain to cervical lymph nodes in normal rats, using Combidex iron oxide-based magnetic resonance imaging (MRI) agent. After intracerebral, intraventricular, intracarotid or intravenous injection of Combidex in normal Long Evans rats, particle localization was assessed by MRI and histochemistry for iron and the dextran coat (n = 27). Intraventricular or intracerebral injection, but not intracarotid administration of Combidex (100 micro g), resulted in MRI signal changes in the deep cervical lymph nodes around the carotid artery, and, less strongly, in the superficial cervical nodes. Within 2 h of Combidex administration, iron was histologically localized in cervical lymph nodes, with patched staining of capsule and peripheral sinus consistent with delivery via multiple afferent lymphatic vessels. Lymph node staining in groups receiving CNS Combidex was significantly different from controls (P < 0.0001) and was significantly localized in the deep vs. superficial cervical lymph nodes (P = 0.0003). The trafficking of the superparamagnetic iron particles from the CNS in the rat could be visualized by MRI and histology. Combidex provides a powerful tool to rapidly assess drainage of virus-sized particles from the CNS.
中枢神经系统（CNS）的引流可能通过与脉管系统的连接发生，但在动物模型中，高达50%的引流是通过血管周围、神经周围以及原始淋巴引流至颈部淋巴结。我们使用基于氧化铁的Combidex磁共振成像（MRI）造影剂，评估了正常大鼠大脑中颗粒向颈部淋巴结的流出情况。在正常的Long Evans大鼠脑内、脑室内、颈内或静脉注射Combidex后，通过MRI和铁及葡聚糖包衣的组织化学方法评估颗粒的定位（n = 27）。脑室内或脑内注射Combidex（100微克）可导致颈动脉周围深层颈部淋巴结的MRI信号改变，浅层颈部淋巴结的信号改变较弱。在注射Combidex后2小时内，铁在组织学上定位于颈部淋巴结，包膜和外周窦的斑片状染色与通过多条传入淋巴管的输送一致。接受中枢神经系统Combidex的组中淋巴结染色与对照组有显著差异（P < 0.0001），且在深层与浅层颈部淋巴结中有显著定位差异（P = 0.0003）。大鼠中枢神经系统中超顺磁性铁颗粒的运输可通过MRI和组织学观察到。Combidex为快速评估病毒大小颗粒从中枢神经系统的引流提供了一个强大的工具。
