Interleukin-1β receptor antagonism prevents cognitive impairment following experimental bacterial meningitis

Tatiana Barichello, Jaqueline S. Generoso, Lutiana R. Simões, Vladislav G. Sharin, Renan A. Ceretta, Diogo Dominguini, Clarissa M. Comim, Márcia C. Vilela, Antonio Lucio Teixeira, João Quevedo

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)253-261
Number of pages9
JournalCurrent Neurovascular Research
Volume12
Issue number3
DOIs
StatePublished - Jul 1 2015
Externally publishedYes

Keywords

  • Bacterial meningitis
  • BDNF
  • Behaviour
  • Cytokines
  • Hippocampus

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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