Abstract (provisional)
Persisting atypical and cystic forms of
Borrelia burgdorferi and local
inflammation in Lyme neuroborreliosis
*Judith Miklossy*, *Sandor Kasas*, *Anne D Zurn*, *Shermann
McCall*, *Sheng Yu* and *Patrick L McGeer*
/Journal of Neuroinflammation/ 2008, *5**:*40doi: 10.1186/1742- 2094-5-40
Background
The long latent stage seen in
syphilis, followed by chronic
central
nervous system infection and inflammation, can be explained by the
persistence of atypical cystic and granular forms of
Treponema pallidum.
We investigated whether a similar situation may occur in Lyme
neuroborreliosis. Method: Atypical forms of Borrelia burgdorferi
spirochetes were induced exposing cultures of Borrelia burgdorferi
(strains B31 and ADB1) to such unfavorable conditions as osmotic and
heat shock, and exposure to the binding agents Thioflavin S and Congo
red. We also analyzed whether these forms may be induced in vitro,
following infection of primary chicken and rat neurons, as well as rat
and human astrocytes. We further analyzed whether atypical forms similar
to those induced in vitro may also occur in vivo, in brains of three
patients with Lyme neuroborreliosis. We used immunohistochemical methods
to detect evidence of neuroinflammation in the form of reactive
microglia and astrocytes. Results: Under these conditions we observed
atypical cystic, rolled and granular forms of these spirochetes. We
characterized these abnormal forms by histochemical,
immunohistochemical , dark field and atomic force microscopy (AFM)
methods. The atypical and cystic forms found in the brains of three
patients with neuropathologically confirmed Lyme neuroborreliosis were
identical to those induced in vitro. We also observed nuclear
fragmentation of the infected astrocytes using the TUNEL method.
Abundant HLA-DR positive microglia and GFAP positive reactive astrocytes
were present in the cerebral cortex.
Conclusion: The results indicate that atypical extra- and intracellular
pleomorphic and cystic forms of Borrelia burgdorferi and local neuroinflammation
occur in the brain in chronic Lyme neuroborreliosis. The persistence of these
more resistant spirochete forms, and their intracellular location in neurons and glial
cells, may explain the long latent stage and persistence of Borrelia
infection. The results also suggest that Borrelia burgdorferi may induce
cellular dysfunction and apoptosis. The detection and recognition of
atypical, cystic and granular forms in infected tissues is essential for
the diagnosis and the treatment as they can occur in the absence of the
typical spiral Borrelia form.