Impairment of the brain beta-adrenergic system during experimental endotoxemia.

Brain dysfunction is observed clinically in patients suffering from prolonged endotoxic shock. However, the etiology of brain dysfunction during sepsis is not clear. Certain researchers have reported that the decrease in brain catecholamines concentration during septic shock might be etiologically important in brain dysfunction. Therefore, we hypothesized that the beta-adrenergic receptor system undergoes a change during septic shock, and plays a role in the pathogenesis of septic encephalopathy. In this study, we examined two models of septic shock in rats, each of which has a different time course for the shock state. Male Wistar rats were divided into four groups: (1) Control--0.9% saline vehicle, (2) Lipopolysaccharide (LPS) i.v.-- Escherichia coli endotoxin 1.0 mg/ml i.v. bolus, (3) Sham-operated, and (4) Cecal ligation and puncture (CLP) model. The rats were killed by decapitation at 3, 12, or 24 hr after the treatments, and the brains were removed and subdivided into three areas: the forebrain, cerebellum, and brain stem. In the LPS i.v. group, the brain tissue norepinephrine (NE) concentration had decreased in the forebrain and brain stem and the tissue epinephrine (E) concentration had decreased in the brain stem by 3 hr after treatment. In the CLP group, the brain tissue NE concentration had decreased in the forebrain, cerebellum, and brain stem (P < 0.05), and the tissue E concentration had decreased in the forebrain and brain stem by 24 hr after treatment (P < 0.05). An alteration in beta-adrenergic receptor density in the forebrain was observed at 24 hr in the CLP group (control, 237.0 +/- 14.0 fmole/mg protein; LPS i.v., 233.2 +/- 3.0 fmole/mg protein; sham-operated, 236.0 +/- 3.0 fmole/mg protein; CLP, 177.0 +/- 4.2 fmole/mg protein). These alterations in transmitter concentrations and beta-adrenergic density in the forebrain may be an important factor in septic encephalopathy.