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

Encephalopathy following sepsis is defined as life-threatening organ failure due to the irregular response of the host to infection and has high mortality and morbidity rates. The present study aimed to investigate the effects of inflammation and the gamma-aminobutyric acid-A (GABA_A) receptor antagonist, bicuculline, on brain tissue in rats with sepsis. Sepsis was experimentally generated using lipopolysaccharide (LPS). The rats were divided into four groups: control, LPS (10 mg/kg i.p.), bicuculline (1.5 mg/kg s.c.), and LPS+Bic. Electrophysiologic recordings and body temperature measurements were completed at the 24th hour, and samples were taken. TNF-α, IL-10, GABA, and MDA levels were measured. Tissue imaging was performed using S100-ß, NEUN, and synaptophysin antibodies. One-way ANOVA followed by the Tukey test was performed for statistical analysis. Inflammatory parameters significantly increased in brain tissue in the LPS group compared with the other groups (TNF-α, [F (3.14) = 6.015, p = 0.042]; IL-10, [F (3.15) = 9.013, p = 0.02]). Tissue imaging results were as follows: S100-ß involvement increased, and NeuN and synaptophysin involvement decreased in the LPS group [F (3.21) = 18.016, p = 0.006, for S100-ß; F (3.21) = 19.071, p = 0.003, for NeuN; F (3.21) = 18.098, p = 0.005, for synaptophysin]. In electrophysiologic recordings, we observed activity consistent with acute non-focal seizures in the LPS group. Contrarily, the control and other comparison groups exhibited normal resting neural activity. Bicuculline may be used as a therapeutic agent in sepsis to maintain the neurotransmitter and pro- and anti-inflammatory cytokine balance and reduce lipid peroxidation with its effects of acetylcholine esterase inhibition and GABA_A receptor antagonism.