Interleukin-18 deficiency and its long-term behavioural and cognitive impacts in a murine model of pneumococcal meningitis.
Behav Brain Res
; 263: 176-89, 2014 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-24503119
ABSTRACT
Pneumococcal meningitis often results in death or neurological sequelae, but the underlying pathogenetic mechanisms remain poorly understood. In C57BL/6J mice subjected to intracerebroventricular (icv) challenge with Streptococcus pneumoniae, the chemokine CCL2 and cytokines interferon-γ, interleukin (IL)-1ß, IL-6 and tumour necrosis factor were prominently expressed in the brain during the acute phase of the disease. The upregulation of these immune mediators was markedly diminished in IL-18-deficient mice. Uninfected IL-18(-/-) mice exhibited decreases in anxiety phenotype and licking behaviour, and an increase in behavioural habituation, in an automated monitoring system (the IntelliCage). Without antibiotic intervention, a majority of IL-18(+/+) mice developed irreversible disease after icv S. pneumoniae but this was significantly improved by deleting IL-18 gene function. IL-18(+/+) mice cured of pneumococcal meningitis with four doses of ceftriaxone, initiated at 20 h post-inoculation, showed enduring sequelae. These included abnormal behavioural phenotypes featuring diurnal hypoactivity and nocturnal hyperactivity, light phobia and disrupted cognitive function. While the hyperactive phenotype was absent in the corresponding IL-18(-/-) survivors, cognitive impairments and behavioural deficits were still present. Overall, the results suggest that the high levels of cytokines and/or chemokines released after pneumococcal challenge provoked a series of pathological events, ultimately causing acute death. Furthermore, since only a subset of behavioural phenotypes were ameliorated in the pneumococcus-infected IL-18(-/-) mice, the pathological pathways causing mortality may be, at least in part, distinct from those leading to long-term neurological sequelae.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ansiedad
/
Trastornos del Conocimiento
/
Interleucina-18
/
Conducta Exploratoria
/
Meningitis Neumocócica
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Behav Brain Res
Año:
2014
Tipo del documento:
Article
País de afiliación:
Australia