Spinal cord involvement in the nonhuman primate model of Lyme disease
Spinal cord involvement in the nonhuman primate model of Lyme disease
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DOI：
10.1038/labinvest.3700024
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发表时间：
2004-02-01
影响因子：
5
通讯作者：
Cadavid, D
中科院分区：
文献类型：
--
作者：
Bai, YH;Narayan, K;Cadavid, D
莱姆病是一种多系统性疾病，由伯氏疏螺旋体的各种基因种感染引起。最常受影响的器官是皮肤、关节、心脏以及中枢和外周神经系统。可发生多种神经系统并发症，包括无菌性脑膜炎、脑病、面神经麻痹、神经根炎、肌萎缩和周围神经病变。为了研究脊髓受累的非人灵长类动物（NHP）模型莱姆病，我们用B接种25只成年猕猴。用针（N=9）或蜱（N=4）或297（N=2）或用B。Burgdorferi基因种garinii菌株Pbi（N=4）、793（N=2）或丸剂（N=4）。使用暂时性（TISP）或永久性（IS）免疫抑制来促进感染的建立。在7-24周后尸检时收集组织和液体。苏木精和伊红染色用于研究炎症，免疫组织化学和数字图像分析用于测量炎症和定位螺旋体。采用TaqMan RT-PCR方法检测螺旋体载量和C1 q表达。结果表明，在25只受检的NHP中，只有一只TISP NHP 321（接种B）发生脑膜神经根炎。加氏菌Pbi.炎症局限于神经根、背根神经节和软脑膜，但很少发生在脊髓实质本身。T细胞和浆细胞是主要的炎性细胞。在炎症脊髓中发现IgG、IgM和C1 q的量显著增加。Taqman RT-PCR仅在IS-NHP的脊髓中发现螺旋体，主要在神经根和神经节中，而不是在脊髓实质中。C1 q mRNA表达在炎症脊髓中显著增加。这是第一个全面的研究脊髓参与莱姆病。
Lyme borreliosis is a multisystemic disease caused by infection with various genospecies of the spirochete Borrelia burgdorferi. The organs most often affected are the skin, joints, the heart, and the central and peripheral nervous systems. Multiple neurological complications can occur, including aseptic meningitis, encephalopathy, facial nerve palsy, radiculitis, myelitis, and peripheral neuropathy. To investigate spinal cord involvement in the nonhuman primate (NHP) model of Lyme borreliosis, we inoculated 25 adult Macaca mulatta with B. burgdorferi sensu strictu strains N40 by needle (N=9) or by tick (N=4) or 297 by needle (N=2), or with B. burgdorferi genospecies garinii strains Pbi (N=4), 793 (N=2), or pill (N=4) by needle. Immunosuppression either transiently (TISP) or permanently (IS) was used to facilitate establishment of infection. Tissues and fluids were collected at necropsy 7-24 weeks later. Hematoxylin and eosin staining was used to study inflammation, and immunohistochemistry and digital image analysis to measure inflammation and localize spirochetes. The spirochetal load and C1q expression were measured by TaqMan RT-PCR. The results showed meningoradiculitis developed in only one of the 25 NHP's examined, TISP NHP 321 inoculated with B. garinii strain Pbi. Inflammation was localized to nerve roots, dorsal root ganglia, and leptomeninges but rarely to the spinal cord parenchyma itself. T cells and plasma cells were the predominant inflammatory cells. Significantly increased amounts of IgG, IgM, and C1q were found in inflamed spinal cord. Taqman RT-PCR found spirochetes in the spinal cord only in IS-NHP's, mostly in nerve roots and ganglia rather than in the cord parenchyma. C1q mRNA expression was significantly increased in inflamed spinal cord. This is the first comprehensive study of spinal cord involvement in Lyme borreliosis.