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Morphological study in the early stages of complement C5a fragment-induced experimental meningitis: activation of
P M Faustmann1, D Krause, R Dux
1Department of Neurology, University of Essen, Germany.
Abstract:
Subarachnoidal application of the complement C5a fragment was used to induce acute experimental meningitis in rabbits and rats within 30-60 min. The early stages of the cellular inflammatory response were studied by means of flow cytometry, transmission electron microscopy and immunofluorescence microscopy. Infiltration of polymorphonuclear leukocytes (PMN) into the subarachnoidal space was the earliest event of the inflammatory reaction. By morphological criteria we found that PMN interacted with cells of the mononuclear-macrophage lineage (MML) and the marginal astrocytes via pseudopodia, whereas the pial cells were not involved in early stages of the inflammatory response. The number of invaded MML that were positive with the ED2 marker increased, indicating the hematogenous origin of the immigrating cell population. PMN were found to infiltrate the perivascular space of the marginal arterial vessel segments. This perivascular infiltration was assumed to be the first manifestation of cerebral vasculitis. The intimate association of resident cerebral cells (astrocytes) with invading PMN and MML is suggestive of a transient interaction of these cell types.
Insights
Complement C5a fragment induces experimental meningitis in rodents. Polymorphonuclear leukocytes infiltrate the subarachnoid space, interacting with resident cells and marking early cerebral vasculitis.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Experimental meningitis models are crucial for understanding central nervous system inflammation.
- The complement system, particularly C5a, plays a role in inflammatory processes.
Purpose of the Study:
- To investigate the early cellular inflammatory response in experimental meningitis induced by complement C5a.
- To characterize the interactions between infiltrating leukocytes and resident brain cells.
Main Methods:
- Induction of meningitis in rabbits and rats using subarachnoidal complement C5a.
- Analysis of cellular infiltration and interactions using flow cytometry, transmission electron microscopy, and immunofluorescence microscopy.
Main Results:
- Polymorphonuclear leukocytes (PMN) were the first cells to infiltrate the subarachnoid space.
- PMN interacted with mononuclear-macrophage lineage (MML) cells and astrocytes.
- Evidence of PMN infiltration into perivascular spaces, suggesting early cerebral vasculitis.
Conclusions:
- Complement C5a rapidly induces experimental meningitis and associated cellular inflammation.
- Early inflammatory response involves PMN infiltration and interaction with resident brain cells.
- Perivascular PMN infiltration may represent the initial stage of cerebral vasculitis in this model.