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.
Highlights
We aim to demonstrate behavioral alterations in a sepsis model using intravenous (IV) immunoglobulin G (IgG) and immunoglobulins enriched with immunoglobulin A (IgA) and IgM (IgGAM)
We recently demonstrated that treatment with intravenous immunoglobulin protects the blood–brain barrier (BBB) integrity and inhibits cecal ligation and puncture (CLP)-induced sickness behavior, and improves survival in septic animals [9]
The results of the behavioral alterations caused by CLP-induced sepsis assessed by open field, elevated plus maze and forced swimming tasks are shown as follows: Elevated plus maze The elevated plus maze (EPM) was performed on the 10th, 30th and 60th days
Summary
We aim to demonstrate behavioral alterations in a sepsis model using intravenous (IV) immunoglobulin G (IgG) and immunoglobulins enriched with IgA and IgM (IgGAM). Acute brain dysfunction is a common complication of sepsis, which has been reported to be associated with adverse outcomes like long-term cognitive impairments. Cognitive consequences of sepsis were tested in septic rats in which survivors showed learning and memory impairment after complete physical recovery in a CLP model [3]. Other experimental studies suggested this model as a clinically relevant method to investigate cognitive impairment in sepsis survivors [4, 5]. Treatments targeted to manipulate the inflammatory pathways have been investigated to influence long-term cognitive deficits in sepsis-induced brain dysfunction. The beneficial effects of antioxidant treatment in long-term memory impairment were reported in a cecal ligation and puncture (CLP) model in rats [4].
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