Anti-inflammatory treatment influences neuronal apoptotic cell death in the dentate gyrus in experimental pneumococcal meningitis.
Apoptotic neuronal death and the increase of neuron-specific enolase (NSE) in cerebrospinal fluid (CSF) were studied in a rabbit model of experimental pneumococcal meningitis after treatment with antimicrobial (ceftriaxone) and antiinflammatory agents (dexamethasone, monoclonal antibodies against the beta-subunit of beta 2-integrins [anti-CD18 mAb]). Twenty-four hours after infection, apoptotic cell death was found solely in the granular cell layer of the dentate gyrus. Neurons with DNA fragmentation were quantified with the in situ tailing (IST) reaction. Dexamethasone and anti-CD18 mAb inhibited the NSE increase in CSF significantly (p = 0.003, p = 0.011). After administration of dexamethasone the density of apoptotic neurons was significantly higher than in control animals receiving only ceftriaxone (p = 0.044). The median of the density of apoptotic neurons was lower in the dentate gyrus in animals receiving anti-CD18 mAb and ceftriaxone vs those receiving only ceftriaxone, although the difference did not reach statistic significance (p = 0.058). In conclusion, apoptotic cell death occurs in the dentate gyrus during the early phase of bacterial meningitis. The extent was influenced by antiinflammatory therapy. The systemic administration of glucocorticoids increased the quantity of apoptotic neurons in the dentate gyrus but reduced overall neuronal damage as indicated by low levels of NSE concentration in CSF.
Zysk
G
G
Department of Neurology, University of Gottingen, Germany.
Brück
W
W
Gerber
J
J
Brück
Y
Y
Prange
H W
HW
Nau
R
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D018891:Dentate Gyrus / Q000166:cytology* / Q000648:ultrastructure; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007773:Lactates / Q000134:cerebrospinal fluid; D008586:Meningitis, Pneumococcal / Q000188:drug therapy* / Q000473:pathology; D008854:Microscopy, Electron; D009474:Neurons / Q000166:cytology* / Q000276:immunology / Q000382:microbiology; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid / Q000494:pharmacology; D011817:Rabbits
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D007773:Lactates; D003907:Dexamethasone; D010751:Phosphopyruvate Hydratase