Skip to main content

Advertisement

Log in

Circulating concentrations, cerebral output of the CINC-1 and blood–brain barrier disruption in Wistar rats after pneumococcal meningitis induction

  • Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Pneumococcal meningitis is a severe infectious illness of the central nervous system (CNS), with high rates of lethality and morbidity, being that the microorganism and the host’s inflammatory response are responsible for cerebral complications. Moreover, the blood–brain barrier (BBB) itself secretes cytokines and, because of the bipolar nature of the BBB, these substances can be secreted into either the CNS compartment or in the blood, so patients with acute bacterial meningitis frequently develop sepsis. Therefore, the aim of this study was to evaluate the cytokine/chemokine levels in different vessels and the BBB integrity after pneumococcal meningitis induction. Wistar rats were infected with Streptococcus pneumoniae, and the BBB integrity was investigated using Evan’s blue dye. Also, blood from the carotid artery and jugular vein was collected in order to perform tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-60 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) analyses by enzyme-linked immunosorbent assay (ELISA). CINC-1 levels were increased at 6 h in the arterial plasma and at 3 and 6 h in the jugular plasma. We observed BBB breakdown between 12 and 24 h in the hippocampus and at 12 and 18 h in the cortex after pneumococcal meningitis induction. The increase of CINC-1 occurred prior to the BBB breakdown. CINC-1 is a neutrophil chemoattractant and it may be related to early events in the pneumococcal meningitis pathophysiology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

BBB:

Blood–brain barrier

CINC-1:

Cytokine-induced neutrophil chemoattractant-1

CFU:

Colony-forming units

CSF:

Cerebrospinal fluid

CNS:

Central nervous system

IL-1β:

Interleukin-1 beta

IL-6:

Interleukin-6

S. pneumoniae :

Streptococcus pneumoniae

TNF-α:

Tumour necrosis factor-alpha

References

  1. Giebink GS (2001) The prevention of pneumococcal disease in children. N Engl J Med 345(16):1177–1183

    Article  PubMed  CAS  Google Scholar 

  2. van de Beek D, de Gans J, Tunkel AR, Wijdicks EF (2006) Community-acquired bacterial meningitis in adults. New Engl J Med 354:44–53

    Article  PubMed  Google Scholar 

  3. Nathan BR, Scheld WM (2000) New advances in the pathogenesis and pathophysiology of bacterial meningitis. Curr Infect Dis Rep 2:332–336

    Article  PubMed  Google Scholar 

  4. Sellner J, Täuber MG, Leib SL (2010) Pathogenesis and pathophysiology of bacterial CNS infections. Handb Clin Neurol 96:1–16

    Article  PubMed  Google Scholar 

  5. Kim KS (2003) Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury. Nat Rev Neurosci 4:376–385

    Article  PubMed  CAS  Google Scholar 

  6. Banks WA, Erickson MA (2010) The blood–brain barrier and immune function and dysfunction. Neurobiol Dis 37(1):26–32

    Article  PubMed  CAS  Google Scholar 

  7. Fabry Z, Fitzsimmons KM, Herlein JA, Moninger TO, Dobbs MB, Hart MN (1993) Production of the cytokines interleukin 1 and 6 by murine brain microvessel endothelium and smooth muscle pericytes. J Neuroimmunol 47(1):23–34

    Article  PubMed  CAS  Google Scholar 

  8. Verma S, Nakaoke R, Dohgu S, Banks WA (2005) Release of cytokines by brain endothelial cells: a polarized response to lipopolysaccharide. Brain Behav Immun 20(5):449–55

    Article  PubMed  Google Scholar 

  9. Møller K, Tofteng F, Qvist T, Sahl C, Sønderkaer S, Pedersen BK (2005) Cerebral output of cytokines in patients with pneumococcal meningitis. Crit Care Med 33(5):979–983

    Article  PubMed  Google Scholar 

  10. Wheeler AP, Bernard GR (1999) Treating patients with severe sepsis. N Engl J Med 340:207–214

    Article  PubMed  CAS  Google Scholar 

  11. Grandgirard D, Steiner O, Täuber MG, Leib SL (2007) An infant mouse model of brain damage in pneumococcal meningitis. Acta Neuropathol 114:609–617

    Article  PubMed  Google Scholar 

  12. Barichello T, dos Santos I, Savi GD, Simões LR, Silvestre T, Comim CM, Sachs D, Teixeira MM, Teixeira AL, Quevedo J (2010) TNF-alpha, IL-1beta, IL-6, and cinc-1 levels in rat brain after meningitis induced by Streptococcus pneumoniae. J Neuroimmunol 221:42–45

    Article  PubMed  CAS  Google Scholar 

  13. Barichello T, dos Santos I, Savi GD, Florentino AF, Silvestre C, Comim CM, Feier G, Sachs D, Teixeira MM, Teixeira AL, Quevedo J (2009) Tumor necrosis factor alpha (TNF-alpha) levels in the brain and cerebrospinal fluid after meningitis induced by Streptococcus pneumoniae. Neurosci Lett 467(3):217–219

    Article  PubMed  CAS  Google Scholar 

  14. Irazuzta JE, Pretzlaff RK, Zingarelli B, Xue V, Zemlan F (2002) Modulation of nuclear factor-kappaB activation and decreased markers of neurological injury associated with hypothermic therapy in experimental bacterial meningitis. Crit Care Med 30:2553–2559

    Article  PubMed  Google Scholar 

  15. Irazuzta J, Pretzlaff RK, Zingarelli B (2008) Caspases inhibition decreases neurological sequelae in meningitis. Crit Care Med 36(5):1603–1606

    Article  PubMed  CAS  Google Scholar 

  16. Smith SL, Hall ED (1996) Mild pre- and posttraumatic hypothermia attenuates blood–brain barrier damage following controlled cortical impact injury in the rat. J Neurotrauma 13(1):1–9

    Article  PubMed  CAS  Google Scholar 

  17. Coimbra RS, Loquet G, Leib SL (2007) Limited efficacy of adjuvant therapy with dexamethasone in preventing hearing loss due to experimental pneumococcal meningitis in the infant rat. Pediatr Res 62(3):291–294

    Article  PubMed  CAS  Google Scholar 

  18. Coimbra RS, Voisin V, de Saizieu AB, Lindberg RL, Wittwer M, Leppert D, Leib SL (2006) Gene expression in cortex and hippocampus during acute pneumococcal meningitis. BMC Biol 4:15

    Article  PubMed  Google Scholar 

  19. Hirst RA, Kadioglu A, O’Callaghan C, Andrew PW (2004) The role of pneumolysin in pneumococcal pneumonia and meningitis. Clin Exp Immunol 138(2):195–201

    Article  PubMed  CAS  Google Scholar 

  20. Barichello T, Pereira JS, Savi GD, Generoso JS, Cipriano AL, Silvestre C, Petronilho F, Dal-Pizzol F, Vilela MC, Teixeira AL (2011) A kinetic study of the cytokine/chemokines levels and disruption of blood–brain barrier in infant rats after pneumococcal meningitis. J Neuroimmunol 233(1–2):12–17

    Article  PubMed  CAS  Google Scholar 

  21. Katayama T, Tanaka H, Yoshida T, Uehara T, Minami M (2009) Neuronal injury induces cytokine-induced neutrophil chemoattractant-1 (CINC-1) production in astrocytes. J Pharmacol Sci 109(1):88–93

    Article  PubMed  CAS  Google Scholar 

  22. Campbell SJ, Wilcockson DC, Butchart AG, Perry VH, Anthony DC (2002) Altered chemokine expression in the spinal cord and brain contributes to differential interleukin-1beta-induced neutrophil recruitment. J Neurochem 83:432–441

    Article  PubMed  CAS  Google Scholar 

  23. Campbell SJ, Hughes PM, Iredale JP, Wilcockson DC, Waters S, Docagne F, Perry VH, Anthony DC (2003) CINC-1 is an acute-phase protein induced by focal brain injury causing leukocyte mobilization and liver injury. FASEB J 17(9):1168–1170

    PubMed  CAS  Google Scholar 

  24. Rosenberg GA, Estrada EY, Dencoff JE, Stetler-Stevenson WG (1995) Tumor necrosis factor-alpha-induced gelatinase B causes delayed opening of the blood–brain barrier: an expanded therapeutic window. Brain Res 703(1–2):151–155

    Article  PubMed  CAS  Google Scholar 

  25. Tureen J (1995) Effect of recombinant human tumor necrosis factor-alpha on cerebral oxygen uptake, cerebrospinal fluid lactate, and cerebral blood flow in the rabbit: role of nitric oxide. J Clin Invest 95(3):1086–1091

    Article  PubMed  CAS  Google Scholar 

  26. Quagliarello VJ, Wispelwey B, Long WJ Jr, Scheld WM (1991) Recombinant human interleukin-1 induces meningitis and blood–brain barrier injury in the rat. Characterization and comparison with tumor necrosis factor. J Clin Invest 87:1360–1366

    Article  PubMed  CAS  Google Scholar 

  27. van Furth AM, Roord JJ, van Furth R (1996) Roles of proinflammatory and anti-inflammatory cytokines in pathophysiology of bacterial meningitis and effect of adjunctive therapy. Infect Immun 64:4883–4890

    PubMed  Google Scholar 

  28. Asano T, Ichiki K, Koizumi S, Kaizu K, Hatori T, Fujino O, Mashiko K, Sakamoto Y, Miyasho T, Fukunaga Y (2010) IL-17 is elevated in cerebrospinal fluids in bacterial meningitis in children. Cytokine 51:101–106

    Article  PubMed  CAS  Google Scholar 

  29. Leib SL, Täuber MG (1999) Pathogenesis of bacterial meningitis. Infect Dis Clin North Am 13:527–548

    Article  PubMed  CAS  Google Scholar 

  30. Baggiolini M, Dewald B, Moser B (1994) Interleukin-8 and related chemotactic cytokines—CXC and CC chemokines. Adv Immunol 55:97–179

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by grants from CNPq, FAPEMIG, FAPESC, UNESC, Instituto Nacional de Ciência e Tecnologia Translacional em Medicina and L´Oréal-UNESCO Brazil Fellowship for Women in Science 2011.

Disclosure

The authors have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T. Barichello.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barichello, T., Generoso, J.S., Silvestre, C. et al. Circulating concentrations, cerebral output of the CINC-1 and blood–brain barrier disruption in Wistar rats after pneumococcal meningitis induction. Eur J Clin Microbiol Infect Dis 31, 2005–2009 (2012). https://doi.org/10.1007/s10096-011-1533-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-011-1533-2

Keywords

Navigation