Article
A simple experimental animal model of cerebral immunomodulation
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Authors
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M. Löhr
- Klinik und Poliklinik für Allgemeine Neurochirurgie, Zentrum für Neurochirurgie, Klinikum der Universität zu Köln
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D. Mohseni
- Klinik und Poliklinik für Allgemeine Neurochirurgie, Zentrum für Neurochirurgie, Klinikum der Universität zu Köln
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G. Tzouras
- Klinik und Poliklinik für Allgemeine Neurochirurgie, Zentrum für Neurochirurgie, Klinikum der Universität zu Köln
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W. Stenzel
- Institut für Neuropathologie, Klinikum der Universität zu Köln
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M. Molcanyi
- Klinik und Poliklinik für Allgemeine Neurochirurgie, Zentrum für Neurochirurgie, Klinikum der Universität zu Köln
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J. Hampl
- Klinik und Poliklinik für Allgemeine Neurochirurgie, Zentrum für Neurochirurgie, Klinikum der Universität zu Köln
| Published: | May 20, 2009 |
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Outline
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Objective: Immune reactions contribute considerably to the genesis and evolution of damage in various neurosurgical diseases like hemorrhage, trauma or tumor. The common immunogenic stimuli in these pathologies are the breakdown of tissue and the release of proinflammatory mediators. To further investigate the sequence of neuroinflammatory events in these conditions, we introduce a new and simple experimental model.
Methods: Sixteen Wistar rats received an intracerebral injection of 1010 inactivated Gram positive bacteria (IGPB), thus combining cellular breakdown with the liberation of proinflammatory cell wall constituents. Animals (n=4 in each group) were perfused on day 1, 4, 7 and 17, respectively. Serial sections of the injection site were stained for ED1, CD4, CD8a, CD11b, CD45, CD161a, dendritic cells, RT1b, GFAP and NeuN.
Results: Injection of IGPB resulted in well-circumscribed intraparenchymal deposits, infiltrated by CD45+ cells as early as day 1, mainly composed of granulocytes in the center and circumjacent macrophages that became the predominating immunocompetent cell type from day 4 on. CD4+ lymphocytes increased gradually in number, developing a scattered infiltrate until day 17, thus indicating the switch from an unspecific to a specific immune response. MHC class II presenting cells were abundantly recruited throughout the hemisphere from day 1 on migrating centripetally to the IGPB deposit and eventually shaping an increasingly dense collection within the lesion. The initially widespread activated microglial response became more condensed by time and eventually formed a circular bank around the IGPB deposit, that was proximately encompassed by a perilesional astrocytic wall.
Conclusions: The immune response evoked by intracerebral admisitration of IGBP is a highly reproducible and standardized procedure to further explore the initiation and maintenance of the cerebral inflammatory response. The technique is straightforward and feasible and facilitates the experimental application of novel immunomodulatory strategies.
