The Effects of Ionotropic GABA Receptor Blockage on the Brain in Rats with Induced Sepsis

Abstract

Abstract Encephalopathy develops following sepsis, which is defined as life-threatening organ failure due to the irregular response of a host to infection. It has high mortality and morbidity rates. In this study, we aimed to investigate the effects of inflammation on brain tissue, and the effects of the gamma-aminobutyric acid-A (GABAA) receptor antagonist bicuculline in rats with sepsis. Sepsis was experimentally generated in rats using lipopolysaccharide (LPS). The rats were divided into four groups as control, LPS (10 mg/kg i.p.), bicuculline (1.5 mg/kg bicuculline methiodide s.c.), and LPS + bicuculline. Electrophysiologic recordings and body temperature measurements were completed at the 24th hour after injection, and blood samples were taken for measurements of biochemical parameters. TNF-α, IL-10, and GABA levels were measured using ELISA, and MDA levels were measured using the Bouge method. Tissue imaging was performed with S100-ß, NEUN, and synaptophysin antibodies using immunofluorescence staining. One-way ANOVA and the Tukey test were used in statistical analysis. Inflammatory parameters significantly increased in brain tissue in the LPS group compared with the other groups. The immunofluorescence staining results in brain tissues were as follows: S-100ß involvement increased, and NeuN and synaptophysin involvement decreased in the LPS group. In electrophysiologic recordings, activity consistent with acute non-focal seizures was observed in the LPS group; however, resting status was seen in the other groups. We suggest that bicuculline methiodide may be a prophylactic agent in sepsis, which causes impaired neurotransmitter balance, increased pro-inflammatory cytokines, lipid peroxidation, and decreased anti-inflammatory cytokine levels.