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

Abstract

BackgroundWe aim to demonstrate behavioral alterations in a sepsis model using intravenous (IV) immunoglobulin G (IgG) and immunoglobulins enriched with IgA and IgM (IgGAM).MethodsWe 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.ResultsThe 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.ConclusionsSepsis caused deterioration on behavioral parameters. Immunoglobulin treatments alleviated the symptoms of functional disturbances and caused early reversal of behavioral deficits in septic animals.

Neuroprotective effects of intravenous immunoglobulin are mediated through inhibition of complement activation and apoptosis in a rat model of sepsis

“…IgGAM preparation showed a better effect on the BBB integrity than a standard IgG preparation in CLP-induced septic model rats [6]. However, both immunoglobulin preparations were equally effective in reversing behavioral deficits induced by sepsis [12]. Similarly, in the current study, there were no remarkable differences between the clinical and molecular effects of two preparations with the exception that IVIgG treatment exerted a more pronounced and prolonged suppression effect on cerebral C5a receptor expression than IVIgGAM treatment.…”

“…Effects of IVIg treatment on sepsis-induced polyneuropathy were previously reported in a retrospective trial [11]. We recently demonstrated that IVIg treatment protects the BBB integrity, inhibits CLP-induced sickness behavior, and improves survival in septic animals [6, 12]. …”

What Animal Models Can Tell Us About Long-Term Psychiatric Symptoms in Sepsis Survivors: a Systematic Review

“…The differences in mainly anxiety-related behaviors are intriguing. First, in both LPS and CLP models, basically the same molecular targets are altered: Cytokines are more frequently reported and generally affect the hippocampus [169, 176-178, 180, 183-188]; microglial activation is reported by Gao et al (2017); blood-brain barrier permeability is mentioned by Ozcan et al (2015) as one of the first mechanisms induced by the CLP model; and a decrease of neurotrophic factors is related by Gao et al (2017). Besides this, oxidative stress [181,184,188], apoptosis [184,185,187], and HPA alterations [182,183] are related (Fig.…”

Long-Term Cognitive Outcomes After Sepsis: a Translational Systematic Review

“…On day 10, the rats presented depressive-like behavior that was prevented by both treatments. However, on day 30 and on day 60 after CLP surgery, the rodents did not present depressive-like behavior [123]. Metformin: It is a drug used to treat type-2 diabetes and it exerts anti-inflammatory and anti-oxidant effect [124,125].…”