Top

Published in:

01-09-2008 | Experimental

Time-dependent behavioral recovery after sepsis in rats

Authors: Lisiane Tuon, Clarissa M. Comim, Fabricia Petronilho, Tatiana Barichello, Ivan Izquierdo, João Quevedo, Felipe Dal-Pizzol

Published in: Intensive Care Medicine | Issue 9/2008

Abstract

Objective

To evaluate the cognitive performance in rats that survived sepsis induced by cecal ligation and puncture (CLP) after 10, 30 and 60 days.

Design

Prospective, controlled experiment.

Setting

Animal basic science laboratory.

Subjects

Male Wistar rats, weighing 300–350 g.

Interventions

The rats were sham-operated or submitted to CLP (sepsis group) with “basic support” (saline, s.c. at 50 mL/kg immediately and 12 h after CLP plus ceftriaxone, s.c. at 30 mg/kg and clindamycin, s.c. at 25 mg/kg 6, 12 and 18 h after CLP).

Measurements and main results

The animals underwent six behavioral tasks 10, 30 and 60 days after surgery: (a) habituation to the open field; (b) inhibitory avoidance task; (c) continuous multiple trials step-down inhibitory avoidance task; (d) object recognition; (e) elevated plus-maze; and (f) forced swimming test. We demonstrated that survivors 10 days after CLP presented deficits on the habituation to the open field, step-down inhibitory avoidance, continuous multiple-trials step-down inhibitory avoidance, object recognition and forced swimming. After 30 days of sepsis induction, survivors maintained deficits on the step-down inhibitory avoidance, continuous multiple-trials step-down inhibitory avoidance and forced swimming. However, after 60 days all behavior deficits were reversed.

Conclusions

These results indicate that the impairment of memory and learning, demonstrated 10 days after the induction of sepsis, persist 30 days after the CLP. The cognitive impairments did not persist after 60 days suggesting that this model can help in the understanding of the biological mechanisms associated with sepsis-induced sickness behavior.

Granja C, Dias C, Costa-Pereira A, Sarmento A (2004) Quality of life of survivors from severe sepsis and septic shock may be similar to that of others who survive critical illness. Crit Care Med 8:91–98CrossRef

Hopkins RO, Weaver LK, Collingridge D, Parkinson RB, Chan KJ, Orme JF Jr (2005) Two-year cognitive, emotional, and quality-of-life outcomes in acute respiratory distress syndrome. Am J Respir Crit Care Med 17:340–347CrossRef

Angus DC, Musthafa AA, Clermont G, Griffin MF, Linde-Zwirble WT, Dremsizov TT, Pinsky MR (2001) Quality-adjusted survival in the first year after the acute respiratory distress syndrome. Am J Respir Crit Care Med 163:1389–1394PubMed

Hopkins RO, Weaver LK, Chan KJ, Orme JF Jr (2004) Quality of life, emotional, and cognitive function following acute respiratory distress syndrome. J Int Neuropsychol Soc 10:1005–1017PubMed

Rothenhausler HB, Ehrentraut S, Stoll C, Schelling G, Kapfhammer HP (2001) The relationship between cognitive performance and employment and health status in long-term survivors of the acute respiratory distress syndrome: results of an exploratory study. Gen Hosp Psychiatry 23:90–96PubMedCrossRef

Messaris E, Memos N, Chatzigianni E, Konstadoulakis MM, Menenakos E, Katsaragakis S, Voumvourakis C, Androulakis G (2004) Time-dependent mitochondrial-mediated programmed neuronal cell death prolongs survival in sepsis. Crit Care Med 32:1764–1770PubMedCrossRef

Barichello T, Fortunato JJ, Vitali AM, Feier G, Reinke A, Moreira JC, Quevedo J, Dal-Pizzol F (2006) Oxidative variables in the rat brain after sepsis induced by cecal ligation and perforation. Crit Care Med 34:886–889PubMedCrossRef

Barichello T, Machado RA, Constantino L, Valvassori SS, Reus GZ, Martins MR, Petronilho F, Ritter C, Quevedo J, Dal-Pizzol F (2007) Antioxidant treatment prevented late memory impairment in an animal model of sepsis. Crit Care Med 35:2186–2190PubMedCrossRef

Barichello T, Martins MR, Reinke A, Feier G, Ritter C, Quevedo J, Dal-Pizzol F (2005) Cognitive impairment in sepsis survivors from cecal ligation, perforation. Crit Care Med 33:221–223PubMedCrossRef

10.

Barichello T, Martins MR, Reinke A, Feier G, Ritter C, Quevedo J, Dal-Pizzol F (2005) Long-term cognitive impairment in sepsis survivors. Crit Care Med 33:1671PubMedCrossRef

11.

Ritter C, Andrades ME, Reinke A, Menna-Barreto S, Moreira JCF, Dal-Pizzol F (2004) Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis. Crit Care Med 32:342–349PubMedCrossRef

12.

Ritter C, Andrades M, Frota Junior ML, Pinho RA, Moreira JCF, Dal-Pizzol F (2003) Oxidative parameters and mortality in sepsis induced by cecal ligation and perforation. Intensive Care Med 29:1782–1789PubMedCrossRef

13.

Andrades M, Ritter C, Moreira JC, Dal-Pizzol F (2005) Oxidative parameters differences during non-lethal and lethal sepsis development. J Surg Res 125:68–72PubMedCrossRef

14.

Vianna MR, Alonso M, Viola H, Izquierdo I (2000) Role of hippocampal signaling pathways in long-term memory formation of a nonassociative learning task in the rat. Learn Mem 7:333–340PubMedCrossRef

15.

Quevedo J, Vianna MR, Roesler R, Izquierdo I (1999) Two time windows of anisomycin-induced amnesia for inhibitory avoidance training in rats: protection from amnesia by pretraining but not pre-exposure to the task apparatus. Learn Mem 6:600–607PubMedCrossRef

16.

Rosa RM, Flores DG, Appelt HR, Braga AL, Henriques JA, Roesler R (2003) Facilitation of long-term object recognition memory by pretraining administration of diphenyl diselenide in mice. Neurosci Lett 341:217–220PubMedCrossRef

17.

Schröder N, O’Dell SJ, Marshall JF (2003) Neurotoxic methamphetamine regimen severely impairs recognition memory in rats. Synapse 49:89–96PubMedCrossRef

18.

Pellow S, Chopin P, File SE, Briley M (1985) Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149–167PubMedCrossRef

19.

Rickels K, Schweizer EE (1987) Current pharmacotherapy in anxiety and panic. In: Meltzer HY (ed) Psychopharmacology: The third generation of progress. Raven, New York, pp 1193–1203

20.

Porsolt RD (1979) Animal model of depression. Biomedicine 30:139–140PubMed

21.

Einat H, Clenet F, Shaldubina A, Belmaker RH, Bourin M (2001) The antidepressant activity of inositol in the forced swim test involves 5-HT(2) receptors. Behav Brain Res 118:77–83PubMedCrossRef

22.

Barichello T, Martins MR, Reinke A, Constantino LS, Machado RA, Valvassori SS, Moreira JC, Quevedo J, Dal-Pizzol F (2007) Behavioral deficits in sepsis-surviving rats induced by cecal ligation and perforation. Braz J Med Biol Res 40:831–837PubMedCrossRef

23.

Sukantarat KT, Burgess PW, Williamson RC, Brett SJ (2005) Prolonged cognitive dysfunction in survivors of critical illness. Anaesthesia 60:847–853PubMedCrossRef

24.

Hopkins RO, Weaver LK, Pope D, Orme JF, Bigler ED, Larson-Lohr V (1999) Neuropsychological sequelae and impaired health status in survivors of severe acute respiratory distress syndrome. Am J Respir Crit Care Med 160:50–56PubMed

25.

Scragg P, Jones A, Fauvel N (2001) Psychological problems following ICU treatment. Anaesthesia 56:9–14PubMedCrossRef

26.

Jackson JC, Hart RP, Gordon SM, Shintani A, Truman B, May L, Ely EW (2003) Six-month neuropsychological outcome of medical intensive care unit patients. Crit Care Med 31:1226–1234PubMedCrossRef

27.

Al-Saidi F, McAndrews MP, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Herridge M (2003) Neuropsychological sequelae in ARDS survivors. Am J Respir Crit Care Med 167:A737

28.

Schelling G, Stoll C, Haller M, Briegel J, Manert W, Hummel T, Lenhart A, Heyduck M, Polasek J, Meier M, Preuss U, Bullinger M, Schuffel W, Peter K (1998) Health-related quality of life and posttraumatic stress disorder in survivors of the acute respiratory distress syndrome. Crit Care Med 26:651–659PubMedCrossRef

29.

Semmler A, Frisch C, Debeir T, Ramanathan M, Thorsten-Okulla A, Klockgether T, Heneka MT (2007) Long-term cognitive impairment, neuronal loss and reduced cortical cholinergic innervation after recovery from sepsis in a rodent model. Exp Neurol 204:733–740PubMedCrossRef

30.

Tuon L, Comim CM, Antunes MM, Constantino LS, Machado RA, Izquierdo I, Quevedo J, Dal-Pizzol F (2007) Imipramine reverses the depressive symptoms in sepsis survivor rats. Intensive Care Med 33:2165–2167PubMedCrossRef

31.

Hopkins RO, Jackson JC (2006) Long-term neurocognitive function after critical illness. Chest 130:869–878PubMedCrossRef

32.

Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9:46–56 PubMedCrossRef

33.

Bauhofer A, Schwarting RK, Köster M, Schmitt A, Lorenz W, Pawlak CR (2004) Sickness behavior of rats with abdominal sepsis can be improved by antibiotic and G-CSF prophylaxis in clinic modeling randomized trials. Inflamm Res 53:697–705PubMedCrossRef

Title: Time-dependent behavioral recovery after sepsis in rats
Authors: Lisiane Tuon
Clarissa M. Comim
Fabricia Petronilho
Tatiana Barichello
Ivan Izquierdo
João Quevedo
Felipe Dal-Pizzol
Publication date: 01-09-2008
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 9/2008
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-008-1129-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Time-dependent behavioral recovery after sepsis in rats

Abstract

Objective

Design

Setting

Subjects

Interventions

Measurements and main results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Design

Setting

Subjects

Interventions

Measurements and main results

Conclusions

Please log in to get access to this content

Other articles of this Issue 9/2008

Trigger performance of mid-level ICU mechanical ventilators during assisted ventilation: a bench study

CPAP and HFOV: different guises of the same underlying intensive care strategy for supporting RSV bronchiolitis

Comparison of lung tissue concentrations of nebulized ceftazidime in ventilated piglets: ultrasonic versus vibrating plate nebulizers

Protein C concentrate to restore physiological values in adult septic patients

Neural trigger and cycling off during helmet pressure support ventilation: the epitome of the perfect patient ventilator interaction?

Does severe non-infectious SIRS differ from severe sepsis?