Long-term intrathecal infusion of outer surface protein C from Borrelia burgdorferi causes axonal damage
| Autor: | Dominik Kugelstadt, Torsten Heinz, Stephanie Bunkowski, Annette Spreer, Sandra Ribes, Helmut Eiffert, Olaf Jahn, Simone C. Tauber, Sandra Ebert, Roland Nau, Volker Fingerle |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Pathology Apoptosis medicine.disease_cause Pathogenesis Mice Drug Interactions Cells Cultured Injections Spinal Neurons Lyme Disease biology Microglia Microfilament Proteins Brain General Medicine Pathophysiology Anti-Bacterial Agents Up-Regulation medicine.anatomical_structure Neurology Tumor Necrosis Factors Bacterial Outer Membrane Proteins medicine.medical_specialty Central nervous system Motor Activity Pathology and Forensic Medicine Cellular and Molecular Neuroscience Antigens CD Polysaccharides medicine Animals Borrelia burgdorferi Maze Learning Neuroinflammation Antigens Bacterial Calcium-Binding Proteins bacterial infections and mycoses biology.organism_classification Chemokine CXCL13 Axons Mice Inbred C57BL Disease Models Animal Lyme Neuroborreliosis Animals Newborn Immunology Borrelia garinii Neurology (clinical) |
| Zdroj: | Journal of neuropathology and experimental neurology. 70(9) |
| ISSN: | 1554-6578 |
| Popis: | Lyme neuroborreliosis (LNB) is the most frequent tick-borne infectious disease of the central nervous system. In acute LNB and the rare chronic state of infection, patients can experience cognitive deficits such as attention and memory disturbances. During LNB, single compounds of Borrelia burgdorferi sensu lato are released into the subarachnoid space. To investigate the pathogenesis of neurologic dysfunction in LNB, we determined that the outer surface protein C (OspC), a major virulence factor of B. burgdorferi , stimulated mouse microglial cells in a dose-dependent manner to release nitric oxide (EC50 = 0.24 mg/L) in vitro. To mimic pathophysiologic conditions of long-term release of this bacterial component in vivo, we treated C57BL/6 mice with recombinant OspC from Borrelia garinii or buffer by intraventricular infusion and tested them for behavioral deficits. After 4weeks, brains were examined by routine histology and immunohistochemistry. Assessment of spatial learning and memory of treated mice during OspC exposure did not reveal significant differences from controls. Continuous exposure to intrathecal B. burgdorferi OspC led to activation of microglia and axonal damage without demonstrable cognitive impairment in experimental mice. These results suggest that long-term intrathecal exposure to OspC resulted in axonal damage that may underlie the neurologic manifestations in chronic LNB. |
| Databáze: | OpenAIRE |
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