Interleukin-1β Receptor Antagonism Prevents Cognitive Impairment Following Experimental Bacterial Meningitis

Author(s): Tatiana Barichello, Jaqueline S. Generoso, Lutiana R. Simoes, Vladislav G. Sharin, Renan A. Ceretta, Diogo Dominguini, Clarissa M. Comim, Marcia C. Vilela, Antonio Lucio Teixeira, Joao Quevedo.

Journal Name: Current Neurovascular Research

Volume 12 , Issue 3 , 2015

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Abstract:

Pneumococcal meningitis is characterized by high rates of mortality and long-term cognitive impairment. In this study, we evaluated the effects of interleukin (IL)-1β receptor antagonist (IL-1Ra) on memory, cytokine, and brainderived neurotrophic factor (BDNF) levels in hippocampus after experimental pneumococcal meningitis. In a first experiment the animals were divided into four groups: control/saline, control treated with IL-1Ra, meningitis/saline, and meningitis treated with IL-1Ra. In the meningitis/saline group IL-1β and cytokine-induced neutrophil chemoattractant-1 (CINC-1) levels increased at 24 h post-infection; adjuvant treatment with IL-1Ra reversed the increased levels in the hippocampus. The levels of tumour necrosis factor-alpha (TNF-α), IL-4, IL-6, IL-10, and BDNF did not change in all groups at 24 h post-infection. In a second experiment, the animals were subjected to behavioural tasks (open field, step-down inhibitory avoidance task, and object recognition task), cytokine, and BDNF levels analysis 10 days after experimental meningitis induction. In the open-field task, the meningitis/saline group did not exhibit difference between the training and test sessions, in the motor and exploratory activity indicating memory injury. The meningitis/IL-1Ra group presented difference between training and test session indicating habituation memory. The meningitis/saline group showed impairment in long-term memory for novel object recognition and in aversive memory. The adjuvant treatment with IL-1Ra prevented memory impairment. After behavioural tasks the hippocampus was evaluated. The levels of IL-4, IL-6, IL-10, and BDNF were maintained elevated 10 days post-infection. CINC-1 levels were elevated only in meningitis/saline group and IL-1β decreased in meningitis/IL-Ra group. The levels of TNF-α did not change at 10 days post-infection. These findings illustrate the anti-inflammatory activity of IL-1Ra inhibitor in the first hours after meningitis induction. Adjuvant treatment with IL-1β receptor antagonist could be a new avenue as therapeutic target during bacterial meningitis.

Keywords: Bacterial meningitis, cytokines, BDNF, hippocampus, behaviour.

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Article Details

VOLUME: 12
ISSUE: 3
Year: 2015
Page: [253 - 261]
Pages: 9
DOI: 10.2174/1567202612666150605122200
Price: $58

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