Objective: To investigate the role of the brain gamma-aminobutyric acid receptor system in septic shock.
Design: Prospective, controlled study.
Setting: Animal laboratory.
Subjects: Twenty-one male Wistar rats (7 wks old) were randomized to three groups: group 1 (n = 7, control); group 2 (n = 7, sham-operated); group 3 (n = 7, cecal ligation and puncture group).
Interventions: Under light ether anesthesia, the rats were treated as described above. Twenty-four hours after treatment, the rats were killed by decapitation. Plasma amino acid concentrations were measured using the collected blood. The brain was excised as rapidly as possible, and separated into forebrain, cerebellum, and brain stem. The brain gamma-aminobutyric acid concentration was measured at each of the three regions. Using 3H-musimol, which is a gamma-aminobutyric acid receptor agonist, as a radioligand, the gamma-aminobutyric receptor densities were measured in these three regions by a radio-receptor assay.
Measurements and main results: The concentrations of the branch-chain amino acids (leucine, isoleucine, valine) were lower in the cecal ligation and puncture group than in the control and sham operated groups. The concentrations of the sulfur-containing amino acids (cysteine and taurine) were increased in the cecal ligation and puncture group compared with the other two groups, but the methionine concentration was increased in the sham-operated and the cecal ligation and puncture groups compared with the control group (p < .05). The plasma gamma-aminobutyric acid concentration was not detectable in any of the three groups. The ammonia concentration was greater in the cecal ligation and puncture group than in the other two groups. There was no significant difference in the brain gamma-aminobutyric acid concentration among the three groups. The maximum number of binding sites in the forebrain of the cecal ligation and puncture group was higher than in the other two groups at both high- and low-affinity sites (control group: high-affinity sites 0.34 +/- 0.03, low-affinity sites 2.93 +/- 0.28; sham-operated group: high-affinity sites 0.35 +/- 0.03, low-affinity sites 2.73 +/- 0.18; cecal ligation and puncture group: high-affinity sites 0.59 +/- 0.13, low-affinity sites 3.53 +/- 0.21; mean +/- SEM pmol/mg protein) (p < .05). There were no significant differences observed in other regions of the brain (cerebellum and brain stem) in the three groups. The dissociation constants for 3H-musimol were almost unchanged in the three groups.
Conclusions: An increase in the gamma-aminobutyric acid-A receptor density was observed in the forebrain of the cecal ligation and puncture model rats. This alteration may be closely related to the pathogenesis of brain dysfunction during septic shock.