Top

Intensive Care Medicine

Published in:

01-01-2005 | Brief Report

Dexamethasone decreases neurological sequelae and caspase activity

Authors: Jose Irazuzta, Robert K. Pretzlaff, Gabrielle deCourten-Myers, Frank Zemlan, Basilia Zingarelli

Published in: Intensive Care Medicine | Issue 1/2005

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.

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 98:2632–2639PubMed

Koedel U, Pfister HW (1999) Oxidative stress in bacterial meningitis. Brain Pathol 9:57–67PubMed

Nau R, Bruck W, Soto A (1999) Apoptosis of neurons in the dentate gyrus in humans suffering from bacterial meningitis. J Neuropathol Exp Neurol 58:3265–3274

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 1:4–19CrossRefPubMed

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 104:57–69CrossRefPubMed

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 55:722–728PubMed

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 14:779–790PubMed

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 30:913–918CrossRefPubMed

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 54:353–357CrossRefPubMed

11.

De Gans J, van de Beek D (2002) Dexamethasone in adults with bacterial meningitis. N Engl J Med 347:1549–1556CrossRefPubMed

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 30:2553–2559CrossRefPubMed

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 913:95–105CrossRefPubMed

14.

Irazuzta J, Milam K, Pretzlaff R, Rowin M, Zingarelli B (2000) Hypothermia as an adjunctive treatment for severe bacterial meningitis. Brain Res 881:88–97CrossRefPubMed

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 99:824–831CrossRefPubMed

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 296:137–140CrossRefPubMed

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 88:2003–2011PubMed

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 868:370–375CrossRefPubMed

19.

Yamashima T (2000) Implication of cysteine proteases calpain, cathepsin and caspase in ischemic neuronal death of primates. Neurobiology 62:273–295CrossRef

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 58:297–303PubMed

Title: Dexamethasone decreases neurological sequelae and caspase activity
Authors: Jose Irazuzta
Robert K. Pretzlaff
Gabrielle deCourten-Myers
Frank Zemlan
Basilia Zingarelli
Publication date: 01-01-2005
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 1/2005
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-004-2462-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Dexamethasone decreases neurological sequelae and caspase activity

Abstract

Objective

Design

Setting

Subjects

Interventions

Measurements and main results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Design

Setting

Subjects

Interventions

Measurements and main results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2005

Prediction of responses to various stimuli during sedation: a comparison of three EEG variables

Differential effects of human atrial natriuretic peptide and furosemide on glomerular filtration rate and renal oxygen consumption in humans

Year in review in intensive care medicine, 2004. I. Respiratory failure, infection, and sepsis

Total and ionized serum magnesium in critically ill patients

Returning home after intensive care: A comparison of symptoms of anxiety and depression in ICU and elective cardiac surgery patients and their relatives

Analysis of blood glucose measurements using capillary and arterial blood samples in intensive care patients