1887

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Volume 63, Issue 1

meningitis induces memory impairment and increases pro-inflammatory host response in the central nervous system of Wistar rats Free

Abstract

meningitis has recently become an increasingly common cause of central nervous system infection. The invasion of bacteria within the subarachnoid space stimulates the release of pro-inflammatory cytokines and chemokines, triggering a host immune response. The aim of the present study was to evaluate memory and pro-inflammatory mediators at different times in the brains of adult Wistar rats with meningitis. The animals were sacrificed at 6, 12, 24, 48 and 96 h after meningitis induction. The hippocampus, frontal cortex and cerebrospinal fluid were isolated to determine the cytokine, chemokine and brain-derived neurotrophic factor (BDNF) levels. In the first 6 and 24 h following meningitis induction, there was a significant increase of the TNF-α, IL-1β, IL-6, cytokine-induced neutrophil chemoattractant-1 and BDNF levels in the central nervous system. Ten days after meningitis induction, cognitive memory was evaluated using an open-field task and step-down inhibitory avoidance task. In the control group, significant differences in behaviour were observed between the training and testing sessions for both tasks, demonstrating habituation and aversive memory. However, the meningitis group did not exhibit any difference between the training and testing sessions in either task, demonstrating memory impairment. As a result of these observations, we believe that the meningitis model may be a good research tool to study the biological mechanisms involved in the pathophysiology of this illness, while recognizing that animal models should be interpreted with caution before extrapolation to the clinic.

  • Received:
  • Accepted:
  • Published Online:
© 2014 SGM
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2014-01-01
2024-04-26
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References

  1. Anisman H., Hayley S. 2012; Inflammatory factors contribute to depression and its comorbid conditions. Sci Signal 5:pe45 [View Article][PubMed]
     [Google Scholar]
  2. Barichello T., Savi G. D., Silva G. Z., Generoso J. S., Bellettini G., Vuolo F., Petronilho F., Feier G., Comim C. M. other authors 2010; Antibiotic therapy prevents, in part, the oxidative stress in the rat brain after meningitis induced by Streptococcus pneumoniae . Neurosci Lett 478:93–96 [View Article][PubMed]
     [Google Scholar]
  3. Barichello T., Fagundes G. D., Generoso J. S., Paula Moreira A., Costa C. S., Zanatta J. R., Simões L. R., Petronilho F., Dal-Pizzol F. other authors 2012a; Brain-blood barrier breakdown and pro-inflammatory mediators in neonate rats submitted meningitis by Streptococcus pneumoniae . Brain Res 1471:162–168 [View Article][PubMed]
     [Google Scholar]
  4. Barichello T., Ceretta R. A., Generoso J. S., Moreira A. P., Simões L. R., Comim C. M., Quevedo J., Vilela M. C., Zuardi A. W. other authors 2012b; Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis. Eur J Pharmacol 697:158–164 [View Article][PubMed]
     [Google Scholar]
  5. Barichello T., Lemos J. C., Generoso J. S., Carradore M. M., Moreira A. P., Collodel A., Zanatta J. R., Valvassori S. S., Quevedo J. 2013; Evaluation of the brain-derived neurotrophic factor, nerve growth factor and memory in adult rats survivors of the neonatal meningitis by Streptococcus agalactiae . Brain Res Bull 92:56–59 [View Article][PubMed]
     [Google Scholar]
  6. Bedford H., de Louvois J., Halket S., Peckham C., Hurley R., Harvey D. 2001; Meningitis in infancy in England and Wales: follow up at age 5 years. BMJ 323:533–536 [View Article][PubMed]
     [Google Scholar]
  7. Bekinschtein P., Cammarota M., Igaz L. M., Bevilaqua L. R., Izquierdo I., Medina J. H. 2007; Persistence of long-term memory storage requires a late protein synthesis- and BDNF-dependent phase in the hippocampus. Neuron 53:261–277 [View Article][PubMed]
     [Google Scholar]
  8. Bevilaqua L. R., Kerr D. S., Medina J. H., Izquierdo I., Cammarota M. 2003; Inhibition of hippocampal Jun N-terminal kinase enhances short-term memory but blocks long-term memory formation and retrieval of an inhibitory avoidance task. Eur J Neurosci 17:897–902 [View Article][PubMed]
     [Google Scholar]
  9. Frey B. N., Andreazza A. C., Ceresér K. M., Martins M. R., Valvassori S. S., Réus G. Z., Quevedo J., Kapczinski F. 2006; Effects of mood stabilizers on hippocampus BDNF levels in an animal model of mania. Life Sci 79:281–286 [View Article][PubMed]
     [Google Scholar]
  10. Grandgirard D., Schürch C., Cottagnoud P., Leib S. L. 2007; Prevention of brain injury by the nonbacteriolytic antibiotic daptomycin in experimental pneumococcal meningitis. Antimicrob Agents Chemother 51:2173–2178 [View Article][PubMed]
     [Google Scholar]
  11. Hoogman M., van de Beek D., Weisfelt M., de Gans J., Schmand B. 2007; Cognitive outcome in adults after bacterial meningitis. J Neurol Neurosurg Psychiatry 78:1092–1096 [View Article][PubMed]
     [Google Scholar]
  12. Irazuzta J. E., Pretzlaff R. K., Zingarelli B., Xue V., Zemlan F. 2002; Modulation of nuclear factor-κB activation and decreased markers of neurological injury associated with hypothermic therapy in experimental bacterial meningitis. Crit Care Med 30:2553–2559 [View Article][PubMed]
     [Google Scholar]
  13. Izquierdo I., Barros D. M., Mello e Souza T., de Souza M. M., Izquierdo L. A., Medina J. H. 1998; Mechanisms for memory types differ. Nature 393:635–636 [View Article][PubMed]
     [Google Scholar]
  14. Jurgens H. A., Johnson R. W. 2012; Environmental enrichment attenuates hippocampal neuroinflammation and improves cognitive function during influenza infection. Brain Behav Immun 26:1006–1016 [View Article][PubMed]
     [Google Scholar]
  15. Kerschensteiner M., Gallmeier E., Behrens L., Leal V. V., Misgeld T., Klinkert W. E., Kolbeck R., Hoppe E., Oropeza-Wekerle R. L. other authors 1999; Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation?. J Exp Med 189:865–870 [View Article][PubMed]
     [Google Scholar]
  16. Kuwahara I., Lillehoj E. P., Lu W., Singh I. S., Isohama Y., Miyata T., Kim K. C. 2006; Neutrophil elastase induces IL-8 gene transcription and protein release through p38/NF-κB activation via EGFR transactivation in a lung epithelial cell line. Am J Physiol Lung Cell Mol Physiol 291:L407–L416 [View Article][PubMed]
     [Google Scholar]
  17. Lee D. H., Geyer E., Flach A. C., Jung K., Gold R., Flügel A., Linker R. A., Lühder F. 2012; Central nervous system rather than immune cell-derived BDNF mediates axonal protective effects early in autoimmune demyelination. Acta Neuropathol 123:247–258 [View Article][PubMed]
     [Google Scholar]
  18. Lewin G. R., Barde Y. A. 1996; Physiology of the neurotrophins. Annu Rev Neurosci 19:289–317 [View Article][PubMed]
     [Google Scholar]
  19. Lu C. H., Chang W. N., Chuang Y. C., Chang H. W. 1999; Gram-negative bacillary meningitis in adult post-neurosurgical patients. Surg Neurol 52:438–443, discussion 443–444 [View Article][PubMed]
     [Google Scholar]
  20. Lu C. H., Chang W. N., Chang H. W. 2002; Klebsiella meningitis in adults: clinical features, prognostic factors and therapeutic outcomes. J Clin Neurosci 9:533–538 [View Article][PubMed]
     [Google Scholar]
  21. Mancebo J., Domingo P., Blanch L., Coll P., Net A., Nolla J. 1986; Post-neurosurgical and spontaneous gram-negative bacillary meningitis in adults. Scand J Infect Dis 18:533–538 [View Article][PubMed]
     [Google Scholar]
  22. Mangi R. J., Quintiliani R., Andriole V. T. 1975; Gram-negative bacillary meningitis. Am J Med 59:829–836 [View Article][PubMed]
     [Google Scholar]
  23. McAfoose J., Baune B. T. 2009; Evidence for a cytokine model of cognitive function. Neurosci Biobehav Rev 33:355–366 [View Article][PubMed]
     [Google Scholar]
  24. Morichi S., Kashiwagi Y., Takekuma K., Hoshika A., Kawashima H. 2013; Expressions of brain-derived neurotrophic factor (BDNF) in cerebrospinal fluid and plasma of children with meningitis and encephalitis/encephalopathy. Int J Neurosci 123:17–23 [View Article][PubMed]
     [Google Scholar]
  25. Mukaida N. 2003; Pathophysiological roles of interleukin-8/CXCL8 in pulmonary diseases. Am J Physiol Lung Cell Mol Physiol 284:L566–L577[PubMed] [CrossRef]
     [Google Scholar]
  26. Pfister H. W., Scheld W. M. 1997; Brain injury in bacterial meningitis: therapeutic implications. Curr Opin Neurol 10:254–259 [View Article][PubMed]
     [Google Scholar]
  27. Quevedo J., Vianna M., Zanatta M. S., Roesler R., Izquierdo I., Jerusalinsky D., Quillfeldt J. A. 1997; Involvement of mechanisms dependent on NMDA receptors, nitric oxide and protein kinase A in the hippocampus but not in the caudate nucleus in memory. Behav Pharmacol 8:713–717 [View Article][PubMed]
     [Google Scholar]
  28. Rattiner L. M., Davis M., Ressler K. J. 2005; Brain-derived neurotrophic factor in amygdala-dependent learning. Neuroscientist 11:323–333 [View Article][PubMed]
     [Google Scholar]
  29. Roesler R., Schröder N., Vianna M. R., Quevedo J., Bromberg E., Kapczinski F., Ferreira M. B. 2003; Differential involvement of hippocampal and amygdalar NMDA receptors in contextual and aversive aspects of inhibitory avoidance memory in rats. Brain Res 975:207–213 [View Article][PubMed]
     [Google Scholar]
  30. Scheld W. M., Koedel U., Nathan B., Pfister H. W. 2002; Pathophysiology of bacterial meningitis: mechanism(s) of neuronal injury. J Infect Dis 186:Suppl 2S225–S233 [View Article][PubMed]
     [Google Scholar]
  31. Schmand B., de Bruin E., de Gans J., van de Beek D. 2010; Cognitive functioning and quality of life nine years after bacterial meningitis. J Infect 61:330–334 [View Article][PubMed]
     [Google Scholar]
  32. Sellner J., Täuber M. G., Leib S. L. 2010; Pathogenesis and pathophysiology of bacterial CNS infections. In Handbook of Clinical Neurology vol. 96 pp. 1–16 Edited by Karen L. R., Allan R. T. Amsterdam: Elsevier; [View Article]
     [Google Scholar]
  33. Tunkel A. R., Scheld W. M. 1993; Pathogenesis and pathophysiology of bacterial meningitis. Clin Microbiol Rev 6:118–136[PubMed]
     [Google Scholar]
  34. Vianna M. R., Alonso M., Viola H., Quevedo J., de Paris F., Furman M., de Stein M. L., Medina J. H., Izquierdo I. 2000; Role of hippocampal signaling pathways in long-term memory formation of a nonassociative learning task in the rat. Learn Mem 7:333–340 [View Article][PubMed]
     [Google Scholar]
  35. Wen L. L., Chiu C. T., Huang Y. N., Chang C. F., Wang J. Y. 2007; Rapid glia expression and release of proinflammatory cytokines in experimental Klebsiella pneumoniae meningoencephalitis. Exp Neurol 205:270–278 [View Article][PubMed]
     [Google Scholar]
  36. Yirmiya R., Goshen I. 2011; Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav Immun 25:181–213 [View Article][PubMed]
     [Google Scholar]
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Klebsiella pneumoniae meningitis induces memory impairment and increases pro-inflammatory host response in the central nervous system of Wistar rats
J. Med. Microbiol. 63, 111 (2014); https://doi.org/10.1099/jmm.0.063289-0
/content/journal/jmm/10.1099/jmm.0.063289-0
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