Top

Published in:

Open Access 01-12-2015 | Research

Effects of intravenous immunoglobulin therapy on behavior deficits and functions in sepsis model

Authors: Perihan Ergin Ozcan, Evren Senturk, Gunseli Orhun, Salih Gumru, Nadir Arican, Nurcan Orhan, Canan Ugur Yılmaz, Mehmet Kaya, Feyza Aricioglu, Figen Esen

Published in: Annals of Intensive Care | Issue 1/2015

Abstract

Background

We aim to demonstrate behavioral alterations in a sepsis model using intravenous (IV) immunoglobulin G (IgG) and immunoglobulins enriched with IgA and IgM (IgGAM).

Methods

We divided 48 Wistar albino rats into five groups: control group, sham-operated group (only antibiotic treatment), cecal ligation and puncture (CLP) group (CLP plus antibiotic treatment), IgG group (250 mg/kg IV IgG) and IgGAM group (250 mg/kg IV IgGAM). Intravenous immunoglobulins were given 5 min after the CLP procedure. Experimental animals put into three behavioral tasks 10, 30 and 60 days after the surgery; to evaluate the locomotor activity, an open field test was performed, elevated plus maze test was used to measure anxiety levels, and depressive state was assessed by forced swimming test. The effects of therapy which were acquired from the results of these tests were used to estimate the behavioral changes after CLP.

Results

The mortality rate of 50% in the septic rats decreased to 30 and 20% with the administration of IgG and IgGAM, respectively. Significant changes on locomotor activity and depressive-like behavior were reported in the sepsis group; on the other hand, the treatment with immunoglobulins reduced the symptoms. Treatment with immunoglobulins attenuated the sepsis-related anxiogenic-like responses. Behavioral alterations returned to normal on day 60 in all groups.

Conclusions

Sepsis caused deterioration on behavioral parameters. Immunoglobulin treatments alleviated the symptoms of functional disturbances and caused early reversal of behavioral deficits in septic animals.

Papadopoulos MC, Lamb FJ, Moss RF, Davies DC, Tighe D, Bennett ED (1999) Faecal peritonitis causes edema and neuronal injury in pig cerebral cortex. Clin Sci 96:461–466PubMedCrossRef

Gaillard PJ, de Boer AB, Breimer DD (2003) Pharmacological investigations on lipopolysaccharide-induced permeability changes in the blood–brain barrier in vitro. Microvasc Res 65:24–31PubMedCrossRef

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

Ritter C, Andrades M, Frota Júnior ML, Bonatto F, Pinho RA, Polydoro M et al (2003) Oxidative parameters and mortality in sepsis induced by cecal ligation and perforation. Intensive Care Med 29:1782–1789PubMedCrossRef

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

Ritter C, Andrades ME, Reinke A, Menna-Barreto S, Moreira JC, 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

Petronilho F, Périco SR, Vuolo F, Mina F, Constantino L, Comim CM et al (2012) Protective effects of guanosine against sepsis-induced damage in rat brain and cognitive impairment. Brain Behav Immun 26:904–910PubMedCrossRef

Tuon L, Comim CM, Petronilho F, Barichello T, Izquierdo I, Quevedo J et al (2008) Memory-enhancing treatments reverse the impairment of inhibitory avoidance retention in sepsis-surviving rats. Crit Care 12:R133PubMedCentralPubMedCrossRef

Esen F, Senturk E, Ozcan PE, Ahishali B, Arican N, Orhan N et al (2012) Intravenous immunoglobulins prevent the breakdown of the blood–brain barrier in experimentally induced sepsis. Crit Care Med 40:1214–1220PubMedCrossRef

10.

Rittirsch D, Huber-Lang MS, Flieri MA, Ward PA (2008) Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc 4:31–36CrossRef

11.

Cao XS, Sun XQ, Zhang S, Wang B, Wu YH, Liu TS et al (2007) Acceleration after-effects on learning and memory in rats: +10 Gz or +6 Gz for 3 min. Neurosci Lett 413:245–248PubMedCrossRef

12.

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

13.

Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336PubMed

14.

Semmler A, Widmann CN, Okulla T, Urbach H, Kaiser M, Widman G et al (2013) Persistent cognitive impairment, hippocampal atrophy and EEG changes in sepsis survivors. J Neurol Neurosurg Psychiatry 84:62–69PubMedCrossRef

15.

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

16.

Comim CM, Constantino LS, Petronilho F, de Souza B, Barichello T, Quevedo J et al (2009) Effects of acute treatment with amphetamine in locomotor activity in sepsis survivor rats. J Neuroimmunol 212:145–147PubMedCrossRef

17.

Cassol-Jr OJ, Comim CM, Petronilho F, Constantino LS, Streck EL, Quevedo J et al (2010) Low dose dexamethasone reverses depressive-like parameters and memory impairment in rats submitted to sepsis. Neurosci Lett 473:126–130PubMedCrossRef

18.

Leite FB, Prediger RD, Silva MV, de Sousa JB, Carneiro FP, Gasbarri A et al (2013) Role of nicotine on cognitive and behavioral deficits in sepsis-surviving rats. Brain Res 1507:74–82PubMedCrossRef

19.

Papadopoulos MC, Davies DC, Moss RF, Tighe D, Bennett ED (2000) Pathophysiology of septic encephalopathy: a review. Crit Care Med 28:3019–3024PubMedCrossRef

20.

Pytel P, Alexander JJ (2009) Pathogenesis of septic encephalopathy. Curr Opin Neurol 22:283–287PubMedCrossRef

21.

Hoffman JN, Fertmann JM, Vollmar B, Laschke MW, Jauch KW, Menger MD (2008) Immunoglobulin M-enriched human intravenous immunoglobulins reduce leukocyte–endothelial cell interactions and attenuate microvascular perfusion failure in normotensive endotoxemia. Shock 29:133–139PubMed

22.

Dantzer R, Kelley KW (1989) Stress and immunity: an integrated view of relationships between the brain and the immune system. Life Sci 44:1995–2008PubMedCrossRef

23.

Yi X, Wang Y, Yu FS (2000) Corneal epithelial tight junctions and their response to lipopolysaccharide challenge. Invest Ophthalmol Vis Sci 41:4093–4100PubMed

24.

Lapointe BM, Herx LM, Gill V, Metz LM, Kubes P (2004) IVIg therapy in brain inflammation: etiology-dependent differential effects on leucocyte recruitment. Brain. 127:2649–2656PubMedCrossRef

25.

Basta M (2008) Ambivalent effect of immunoglobulins on the complement system: activation versus inhibition. Mol Immunol 45:4073–4079PubMedCrossRef

26.

Flierl MA, Stahel PF, Rittirsch D, Huber-Lang M, Niederbichler AD, Hoesel LM et al (2009) Inhibition of complement C5a prevents breakdown of the blood brain barrier and pituitary dysfunction in experimental sepsis. Crit Care 13:R12PubMedCentralPubMedCrossRef

27.

Arumugam TV, Woodruff TM, Lathia JD, Selvaraj PK, Mattson MP, Taylor SM (2009) Neuroprotection in stroke by complement inhibition and immunoglobulin therapy. Neuroscience 158:1074–1089PubMedCentralPubMedCrossRef

28.

Garbett ND, Matharu GS, Cole PJ (1989) Defective opsonization of Haemophilus influenzae by sera of elderly patients. Clin Exp Immunol 76:73–75PubMedCentralPubMed

29.

Trautmann M, Held TK, Susa M, Karajan MA, Wulf A, Cross AS et al (1998) Bacterial lipopolysaccharide (LPS)-specific antibodies in commercial human immunoglobulin preparations: superior antibody content of an IgM-enriched product. Clin Exp Immunol 111:81–90PubMedCentralPubMedCrossRef

30.

Stehr SN, Knels L, Weissflog C, Schober J, Haufe D, Lupp A et al (2008) Effects of IGM-Enriched solution on polymorphonuclear neutrophil function, bacterial clearance, and lung histology in endotoxemia. Shock 29:167–172PubMed

31.

Shields RL, Namenuk AK, Hong K, Meng YG, Rae J, Briggs J et al (2001) High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. J Biol Chem 276:6591–6604PubMedCrossRef

Title: Effects of intravenous immunoglobulin therapy on behavior deficits and functions in sepsis model
Authors: Perihan Ergin Ozcan
Evren Senturk
Gunseli Orhun
Salih Gumru
Nadir Arican
Nurcan Orhan
Canan Ugur Yılmaz
Mehmet Kaya
Feyza Aricioglu
Figen Esen
Publication date: 01-12-2015
Publisher: Springer Paris
Published in: Annals of Intensive Care / Issue 1/2015
Electronic ISSN: 2110-5820
DOI: https://doi.org/10.1186/s13613-015-0062-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effects of intravenous immunoglobulin therapy on behavior deficits and functions in sepsis model

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2015

Addition of dexmedetomidine to benzodiazepines for patients with alcohol withdrawal syndrome in the intensive care unit: a randomized controlled study

The use of a novel cleaning closed suction system reduces the volume of secretions within the endotracheal tube as assessed by micro-computed tomography: a randomized clinical trial

Late evaluation of upper limb arterial flow in patients after long radial (PiCCO™) catheter placement

Breakthrough in cardiac arrest: reports from the 4th Paris International Conference

Automatic versus manual changeovers of norepinephrine infusion pumps in critically ill adults: a prospective controlled study

Predictive value of EEG-awakening for behavioral awakening from coma