Behavioral deficits in sepsis-surviving rats induced by cecal ligation and perforation.

Sepsis and its complications are the leading causes of mortality in intensive care units, accounting for 10-50% of deaths. Intensive care unit survivors present long-term cognitive impairment, including alterations in memory, attention, concentration, and/or global loss of cognitive function. In the present study, we investigated behavioral alterations in sepsis-surviving rats. One hundred and ten male Wistar rats (3-4 months, 250-300 g) were submitted to cecal ligation and puncture (CLP), and 44 were submitted to sham operation. Forty-four rats (40%) survived after CLP, and all sham-operated animals survived and were used as control. Twenty animals of each group were used in the object recognition task (10 in short-term memory and 10 in long-term memory), 12 in the plus-maze test and 12 in the forced swimming test. Ten days after surgery, the animals were submitted individually to an object recognition task, plus-maze and forced swimming tests. A significant impairment of short- and long-term recognition memory was observed in the sepsis group (recognition index 0.75 vs 0.55 and 0.74 vs 0.51 for short- and long-term memory, respectively (P < 0.05). In the elevated plus-maze test no difference was observed between groups in any of the parameters assessed. In addition, sepsis survivors presented an increase in immobility time in the forced swimming test (180 vs 233 s, P < 0.05), suggesting the presence of depressive-like symptoms in these animals after recovery from sepsis. The present results demonstrated that rats surviving exposure to CLP, a classical sepsis model, presented recognition memory impairment and depressive-like symptoms but not anxiety-like behavior.

[1]  M. Heneka,et al.  Systemic inflammation induces apoptosis with variable vulnerability of different brain regions , 2005, Journal of Chemical Neuroanatomy.

[2]  J. Quevedo,et al.  Long-term cognitive impairment in sepsis survivors. , 2005, Critical care medicine.

[3]  E. Abraham,et al.  Year in review in Critical Care, 2004: sepsis and multi-organ failure , 2005, Critical care.

[4]  J. Curtis,et al.  Long-term sequelae of critical illness: memories and health-related quality of life , 2005, Critical care.

[5]  Karen J. Chan,et al.  Two-year cognitive, emotional, and quality-of-life outcomes in acute respiratory distress syndrome. , 2005, American journal of respiratory and critical care medicine.

[6]  A. Costa-Pereira,et al.  Patients' recollections of experiences in the intensive care unit may affect their quality of life , 2005, Critical care.

[7]  J. Quevedo,et al.  Cognitive impairment in sepsis survivors from cecal ligation and perforation* , 2005, Critical care medicine.

[8]  R. Hopkins,et al.  Clinical identification of cognitive impairment in ICU survivors: insights for intensivists , 2004, Intensive Care Medicine.

[9]  R. Hopkins,et al.  Research issues in the evaluation of cognitive impairment in intensive care unit survivors , 2004, Intensive Care Medicine.

[10]  A. Costa-Pereira,et al.  Quality of life of survivors from severe sepsis and septic shock may be similar to that of others who survive critical illness , 2004, Critical care.

[11]  Michael E. Andrades,et al.  Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis* , 2004, Critical care medicine.

[12]  J. D. McGaugh,et al.  Glucocorticoid effects on object recognition memory require training-associated emotional arousal. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[13]  H. Manji,et al.  The Role of the Extracellular Signal-Regulated Kinase Signaling Pathway in Mood Modulation , 2003, The Journal of Neuroscience.

[14]  S. O'dell,et al.  Neurotoxic methamphetamine regimen severely impairs recognition memory in rats , 2003, Synapse.

[15]  F. Klamt,et al.  Oxidative parameters and mortality in sepsis induced by cecal ligation and perforation , 2003, Intensive Care Medicine.

[16]  R. Roesler,et al.  Facilitation of long-term object recognition memory by pretraining administration of diphenyl diselenide in mice , 2003, Neuroscience Letters.

[17]  R. Hotchkiss,et al.  The pathophysiology and treatment of sepsis. , 2003, The New England journal of medicine.

[18]  Kevin B Baker,et al.  Effects of stress and hippocampal NMDA receptor antagonism on recognition memory in rats. , 2002, Learning & memory.

[19]  D C Angus,et al.  Quality-adjusted survival in the first year after the acute respiratory distress syndrome. , 2001, American journal of respiratory and critical care medicine.

[20]  M. Bourin,et al.  The antidepressant activity of inositol in the forced swim test involves 5-HT2 receptors , 2001, Behavioural Brain Research.

[21]  D. Heyland,et al.  Long-term health-related quality of life in survivors of sepsis. Short Form 36: A valid and reliable measure of health-related quality of life , 2000, Critical care medicine.

[22]  J. Goodhouse,et al.  Enrichment induces structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice , 2000, Nature Neuroscience.

[23]  E. Shimizu,et al.  Genetic enhancement of learning and memory in mice , 1999, Nature.

[24]  E. Bigler,et al.  Neuropsychological sequelae and impaired health status in survivors of severe acute respiratory distress syndrome. , 1999, American journal of respiratory and critical care medicine.

[25]  Keyue Liu,et al.  Sepsis facilitates brain serotonin activity and impairs learning ability in rats , 1999, Brain Research.

[26]  J. Vincent,et al.  Has the mortality of septic shock changed with time. , 1998, Critical care medicine.

[27]  T. Bleck,et al.  Neurologic complications of critical medical illnesses , 1993, Critical care medicine.

[28]  A. Ennaceur,et al.  A new one-trial test for neurobiological studies of memory in rats. III. Spatial vs. non-spatial working memory , 1992, Behavioural Brain Research.

[29]  Y. Archibald,et al.  The encephalopathy associated with septic illness. , 1990, Clinical and investigative medicine. Medecine clinique et experimentale.

[30]  Michael F. Wilson,et al.  Impact of encephalopathy on mortality in the sepsis syndrome. The Veterans Administration Systemic Sepsis Cooperative Study Group. , 1990, Critical care medicine.

[31]  A. Groeneveld,et al.  Age, chronic disease, sepsis, organ system failure, and mortality in a medical intensive care unit. , 1990, Critical care medicine.

[32]  J. Delacour,et al.  A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data , 1988, Behavioural Brain Research.

[33]  S. File,et al.  Validation of open : closed arm entries in an elevated plus-maze as a measure of anxiety in the rat , 1985, Journal of Neuroscience Methods.

[34]  Porsolt Rd Animal model of depression. , 1979 .

[35]  R. Takahashi,et al.  An animal model of depression. , 1974, Biological psychiatry.

[36]  C. Brun-Buisson,et al.  The epidemiology of the systemic inflammatory response , 2000, Intensive Care Medicine.

[37]  J. Krystal,et al.  Psychopharmacology: The Third Generation of Progress , 1989, The Yale Journal of Biology and Medicine.