Intensive Care Medicine

, Volume 31, Issue 1, pp 146–150 | Cite as

Dexamethasone decreases neurological sequelae and caspase activity

  • Jose Irazuzta
  • Robert K. Pretzlaff
  • Gabrielle deCourten-Myers
  • Frank Zemlan
  • Basilia Zingarelli
Brief Report

Abstract

Objective

To evaluate the use of dexamethasone in a model of meningitis-induced brain injury. Changes in neurobehavioral performance were the primary outcome variables. Changes in caspase activation and markers of neuronal injury were the secondary outcome variables.

Design

Randomized, prospective animal study.

Setting

University research laboratory.

Subjects

Male Wistar rats.

Interventions

Animals underwent a basilar cistern injection of either placebo or a suspension of Group B Streptococcus. Sixteen hours after inoculation, animals were randomized and received either dexamethasone or placebo in addition to antibiotics. Neurobehavioral performance and biological markers of brain injury were assessed at 3 days and 9 days after randomization. In a second experiment, caspase 1 and 3 were evaluated at 6 h, 24 h, and 72 h after dexamethasone administration.

Measurements and main results

Neurobehavioral performance at 3 days and 9 days was significantly improved in the dexamethasone group. Serum C-tau and cerebral edema were decreased after 3 days of dexamethasone treatment. Dexamethasone decreased Caspase 3 activation in meningitic animals.

Conclusion

These findings demonstrate that dexamethasone decreases acute brain injury in a rat model of bacterial meningitis as measured by preservation of neurobehavioral performance.

Keywords

Meningitis Brain injury Caspase Neurobehavioral performance 

References

  1. 1.
    Leib SL, Chow LL, Kim YS, Sheldon RA, Tauber MG (1996) Reactive oxygen intermediates contribute to necrotic and apoptotic neuronal injury in an infant rat model of bacterial meningitis due to group B streptococci. J Clin Invest 98:2632–2639PubMedGoogle Scholar
  2. 2.
    Koedel U, Pfister HW (1999) Oxidative stress in bacterial meningitis. Brain Pathol 9:57–67PubMedGoogle Scholar
  3. 3.
    Nau R, Bruck W, Soto A (1999) Apoptosis of neurons in the dentate gyrus in humans suffering from bacterial meningitis. J Neuropathol Exp Neurol 58:3265–3274Google Scholar
  4. 4.
    Kochanek PM, Adelson PD, Bell MJ, Clark RSB, Jenkins LW, Marion DW, Robertson CL, Ruppel RA, Satchell MA, Seidberg NA, Whalen MJ (2000) Biochemical, cellular, and molecular mechanisms in the evolution of secondary damage after severe traumatic brain injury in infants and children: lessons learned from the bedside. Pediatr Crit Care Med 1:4–19CrossRefPubMedGoogle Scholar
  5. 6.
    Haynes LE, Barber DJ, Griffiths MR, Hyde RE, Mitchell IJ (2001) Dexamethasone induces limited apoptosis and extensive sublethal damage to specific subregions of the striatum and hippocampus: implications for mood disorders. Neuroscience 104:57–69CrossRefPubMedGoogle Scholar
  6. 7.
    Zysk G, Bruck W, Bruck Y, Gerber J, Nau R, Prange HW (1996) Anti-inflammatory treatment influences neuronal apoptotic cell death in the dentate gyrus in experimental pneumococcal meningitis. J Neuropathol Exp Neurol 55:722–728PubMedGoogle Scholar
  7. 8.
    Almeida OFX, Conde GL, Crochemore C, Demeneix BA, Fischer D, Hassan AHS, Holsboer F, Meyer M, Michaelidis TM (2000) Subtle shifts in the ratio between pro- and antiapoptotic molecules after activation of corticosteroid receptors decide neuronal fate. FASEB J 14:779–790PubMedGoogle Scholar
  8. 9.
    Yang JT, Chang CN, Hsu JC, Hsu YH, Lee TH, Lin TN, Wu JH (2002) Effect of dexamethasone on the expression of brain-derived neurotrophic factor and neurotrophin-3 messenger ribonucleic acids after forebrain ischemia in the rat. Crit Care Med 30:913–918CrossRefPubMedGoogle Scholar
  9. 10.
    Leib SL, Heimgartner C, Bifrare YD, Loeffler JM, Tauber MG (2003) Dexamethasone aggravates hippocampal apoptosis and learning deficiency in pneumococcal meningitis in rats. Pediatr Res 54:353–357CrossRefPubMedGoogle Scholar
  10. 11.
    De Gans J, van de Beek D (2002) Dexamethasone in adults with bacterial meningitis. N Engl J Med 347:1549–1556CrossRefPubMedGoogle Scholar
  11. 12.
    Irazuzta J, Pretzlaff R, Xue V, Zemlan F, Zingarelli B (2002) Modulation of NF-kB activation and decreased markers of neurological injury associated with hypothermic therapy in experimental bacterial meningitis. Crit Care Med 30:2553–2559CrossRefPubMedGoogle Scholar
  12. 13.
    Irazuzta J, Bekkedal M, de Courten-Myers G, Rossi J, Zemlan F (2001) Serum cleaved Tau protein and neurobehavioral battery of tests as markers of brain injury in experimental bacterial meningitis. Brain Res 913:95–105CrossRefPubMedGoogle Scholar
  13. 14.
    Irazuzta J, Milam K, Pretzlaff R, Rowin M, Zingarelli B (2000) Hypothermia as an adjunctive treatment for severe bacterial meningitis. Brain Res 881:88–97CrossRefPubMedGoogle Scholar
  14. 15.
    Vanags DM, Orrenius S, Aguilar-Santelises M (1997) Alterations in Bcl-2/Bax protein levels in platelets form part of an ionomycin-induced process that resembles apoptosis. Br J Haematol 99:824–831CrossRefPubMedGoogle Scholar
  15. 16.
    Wellmer A, Noeske C, Gerber J, Munzel U, Nau R (2000) Spatial memory and learning deficits after experimental pneumococcal meningitis in mice. Neurosci Lett 296:137–140CrossRefPubMedGoogle Scholar
  16. 17.
    Saez-Llorens X, Hansen EJ, Jafari HS, McCracken GH Jr, Olsen KD, Parras F, Severien F, Singer LL (1991) Enhanced attenuation of meningeal inflammation and brain edema by concomitant administration of anti-CD18 monoclonal antibodies and dexamethasone in experimental Haemophilus meningitis. J Clin Invest 88:2003–2011PubMedGoogle Scholar
  17. 18.
    Hu W, Jones S, Kharlamov A, Perez-Trepichio A, Wang Y (2000) Directed sampling for electrolyte analysis and water content of micro-punch samples shows large differences between normal and ischemic rat brain cortex. Brain Res 868:370–375CrossRefPubMedGoogle Scholar
  18. 19.
    Yamashima T (2000) Implication of cysteine proteases calpain, cathepsin and caspase in ischemic neuronal death of primates. Neurobiology 62:273–295CrossRefGoogle Scholar
  19. 20.
    Terzic N, Kanazir DT, Krstic-Demonacos M, Milanvic D, Ristic-Fira A, Ruzdijic S, Vujcic M (2003) Effects of age and dexamethasone treatment on glucocorticoid response element and activating protein-1 binding activity in rat brain. J Gerontol A Biol Sci Med Sci 58:297–303PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Jose Irazuzta
    • 1
  • Robert K. Pretzlaff
    • 2
  • Gabrielle deCourten-Myers
    • 3
  • Frank Zemlan
    • 4
  • Basilia Zingarelli
    • 5
  1. 1.Division of Critical Care MedicineThe Floating Hospital for ChildrenBoston 02111USA
  2. 2.Department of PediatricsSection of Critical Care MedicineSacramentoUSA
  3. 3.Professor of NeuropathologyUniversity of CincinnatiCincinnatiUSA
  4. 4.Department of PsychiatryUniversity of CincinnatiCincinnatiUSA
  5. 5.Division of Critical Care MedicineChildren’s Hospital Medical Center and the Children’s Hospital Research FoundationCincinnatiUSA

Personalised recommendations