Organotypic hippocampal cultures - A model of brain tissue damage in Streptococcus pneumoniae meningitis

Hippocampal slices of newborn rats were exposed to either heat-inactivated Streptococcus pneumoniae R6 (hiR6) equivalent to 10(6) and 10(8) CFU/ml, li poteichoic acid (LTA) (0.3 mug/ml and 30 mug/ml), peptidoglycans (PG) (0.3, 30, 50 and 100 mug/ml), pneumococcal DNA (pDNA) (0.3 and 30 mug/ml) or med ium only (control). Cell injury was examined by Nissl staining, Annexin V a nd NeuN immunohistochemistry, and quantified by propidium iodide (PI) uptak e and by determining neuron-specific enolase (NSE) concentration in the cul ture medium. Necrotic and apoptotic cell damage occurred in all treatment g roups. Overall damage (Nissl and PI staining) was most prominent after hiR6 (10(8) CFU/ml), followed by LTA (30 mug/ml), pDNA (30 mug/ml), and not det ectable after PG (30 mug/ml) exposure. PG (100 mug/ml) induced severe damag e. Apoptotic cells were most frequent after exposure to LTA and hiR6. Damag e in the neuronal cell layers (NeuN, NSE) was most severe after treatment w ith hiR6 (10(8) CFU/ml), followed by PG (100 mug/ml), pDNA (30 mug/ml), and LTA (30 mug/ml). (C) 2001 Elsevier Science B.V. All rights reserved.