title: Spinal cord involvement in the nonhuman primate model of Lyme disease.
abstract: 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 Pli (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.
authors.affiliation: Department of Neurology and Neuroscience, and Center for the Study of Emerging Pathogens, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Yunhong
authors.initials: Y
authors.lastname: Bai
authors.forename: Kavitha
authors.initials: K
authors.lastname: Narayan
authors.forename: Donna
authors.initials: D
authors.lastname: Dail
authors.forename: Marie
authors.initials: M
authors.lastname: Sondey
authors.forename: Emir
authors.initials: E
authors.lastname: Hodzic
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Barthold
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Pachner
authors.forename: Diego
authors.initials: D
authors.lastname: Cadavid
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000907:Antibodies, Bacterial / Q000032:analysis; D001733:Bites and Stings; D025065:Borrelia burgdorferi / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology*; D015922:Complement C1q / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D007091:Image Processing, Computer-Assisted; D016867:Immunocompromised Host; D007124:Immunoenzyme Techniques; D007165:Immunosuppression Therapy; D018884:Ixodes / Q000382:microbiology; D020852:Lyme Neuroborreliosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008253:Macaca mulatta; D012329:RNA, Bacterial / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000382:microbiology / Q000473:pathology*
chemical_list: D000893:Anti-Inflammatory Agents; D000907:Antibodies, Bacterial; D012329:RNA, Bacterial; D003907:Dexamethasone; D015922:Complement C1q