Page 71 - Human Lyme Neuroborreliosis

Non-human Primate Animal Models 55

criteria [9] for the immunodiagnosis of long-term B. burgdorferi infection.
Those most commonly recognized in the inoculated monkeys were 18, 21, 30,
39, 45, 58 and 93 KD. Together with the reports of Pachner and coauthors [5,
6] that demonstrated CNS infection of rhesus macaques inoculated with the
N40 strain of B. burgdorferi, the NHP model of Lyme disease appeared to be a
major advance in the experimental study of human LNB. The fundamental
mechanisms for Lyme-associated peripheral neuropathy were not well
appreciated but the multifocal nature and perivascular infiltrates suggested an
immune-mediated inflammatory etiopathogenesis with associated angiopathy
of epineurial, perineurial, and endoneurial blood vessels. A mechanism of
molecular mimicry was suggested by the prior finding of dorsal root ganglia
that stained positively with the highly specific anti-B. burgdorferi 7.5-KD
lipoprotein monoclonal antibody [10]. A minor role for direct PNS infection
was suggested by the finding of several intraneural macrophages that
immunostained positively with highly specific anti-B. burgdorferi 7.5-KD
lipoprotein monoclonal antibody.

Roberts and colleagues [11] studied PNS manifestations of early and late
LNB in rhesus macaques infected with the JD1 strain of B. burgdorferi in
which infection was proven by culture or PCR analysis of skin biopsies or
indirectly by p.i. Western blot analysis. Three months after infection, neuritis
involving endoneurial vessels of multiple nerves were the most consistent PNS
manifestation with both macrophage and B-cell but not T-cell cellular
infiltrates. There were features of demyelination and axonal phagocytosis with
immunohistochemically visualized B. burgdorferi antigens present within
macrophages. Forty-six months after infection, the most common nerve
features were aberrant nerve regeneration, irregularly sized myelinated fibers
and fibrosis. However, even at this late stage, B. burgdorferi were found in
macrophages in endoneurial nerve lesions. Schwann cells that stained
positively for anti-tumor necrosis factor (TNF)-??and anti-nitrotyrosine
antibodies appeared to be the focus of an autoimmune attack or participated in
immunomodulatory phenomena, manifested by the production of interleukin
(IL)-1, IL-6, and TNF-??cytokines. Persistence of B. burgdorferi, most often
noted in infiltrating macrophages in early dissemination, and in isolated foci in
the late phase of infection, was considered necessary to initiate and sustain
active inflammatory lesions.

Pachner and coinvestigators [12] compared the ability of PCR and culture
to detect the presence of spirochetes in the CSF and brain tissue of infected
NHP employing the mouse infectivity test (MIT). Two NHP were treated
orally with 2 mg/kg of body weight of dexamethasone for 1 week then 1

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