PMID- 24503119
OWN - NLM
STAT- MEDLINE
DCOM- 20141203
LR  - 20140305
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 263
DP  - 2014 Apr 15
TI  - Interleukin-18 deficiency and its long-term behavioural and cognitive impacts in 
      a murine model of pneumococcal meningitis.
PG  - 176-89
LID - S0166-4328(14)00049-7 [pii]
LID - 10.1016/j.bbr.2014.01.035 [doi]
AB  - 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-gamma, interleukin (IL)-1beta, 
      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.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Too, L K
AU  - Too LK
AD  - Molecular Immunopathology Unit, Bosch Institute and School of Medical Sciences, 
      University of Sydney, Sydney, NSW 2006, Australia.
FAU - Mitchell, A J
AU  - Mitchell AJ
AD  - The Centenary Institute, Newtown, NSW 2042, Australia.
FAU - Yau, B
AU  - Yau B
AD  - Molecular Immunopathology Unit, Bosch Institute and School of Medical Sciences, 
      University of Sydney, Sydney, NSW 2006, Australia.
FAU - Ball, H J
AU  - Ball HJ
AD  - Molecular Immunopathology Unit, Bosch Institute and School of Medical Sciences, 
      University of Sydney, Sydney, NSW 2006, Australia.
FAU - McGregor, I S
AU  - McGregor IS
AD  - School of Psychology, University of Sydney, Sydney, NSW 2006, Australia.
FAU - Hunt, N H
AU  - Hunt NH
AD  - Molecular Immunopathology Unit, Bosch Institute and School of Medical Sciences, 
      University of Sydney, Sydney, NSW 2006, Australia. Electronic address: 
      Nicholas.hunt@sydney.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140203
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-18)
RN  - 75J73V1629 (Ceftriaxone)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/therapeutic use
MH  - Anxiety/etiology/*physiopathology
MH  - Ceftriaxone/therapeutic use
MH  - Chemokines/cerebrospinal fluid
MH  - Circadian Rhythm/physiology
MH  - Cognition Disorders/etiology/*physiopathology
MH  - Cytokines/cerebrospinal fluid
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Drinking Behavior/physiology
MH  - Exploratory Behavior/*physiology
MH  - Female
MH  - Habituation, Psychophysiologic/physiology
MH  - Interleukin-18/genetics/*metabolism
MH  - Meningitis, Pneumococcal/complications/drug therapy/immunology/*physiopathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Motor Activity/physiology
MH  - Photic Stimulation
OTO - NOTNLM
OT  - Cytokine
OT  - IntelliCage
OT  - Interleukin-18
OT  - Neurological sequelae
OT  - Pneumococcal meningitis
EDAT- 2014/02/08 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/02/08 06:00
PHST- 2013/11/08 00:00 [received]
PHST- 2014/01/21 00:00 [revised]
PHST- 2014/01/24 00:00 [accepted]
PHST- 2014/02/08 06:00 [entrez]
PHST- 2014/02/08 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - S0166-4328(14)00049-7 [pii]
AID - 10.1016/j.bbr.2014.01.035 [doi]
PST - ppublish
SO  - Behav Brain Res. 2014 Apr 15;263:176-89. doi: 10.1016/j.bbr.2014.01.035. Epub 
      2014 Feb 3.