Protective effects of vagus nerve stimulation on rats with sepsis-associated encephalopathy

Abstract

To observe the effects of electrical stimulation of the vagus nerve on sepsis-associated encephalopathy, and to explore its possible mechanism. Forty adult male Sprague-Dawley (SD) rats were randomly divided into sham group, model group, vagotomy group (VGX group), vagus nerve stimulation group (VNS group), with 10 rats in each group. The rat model of sepsis was reproduced by injecting lipopolysaccharide (LPS) through femoral vein, and rats of sham group were given the same volume of normal saline. The left cervical vagotomy was performed 30 minutes before LPS administration in VGX group, electrical stimulation of the left vagus nerve was initiated 30 minutes after LPS administration in VNS group. The rats in sham group were sacrificed after receiving electroencephalogram (EEG) examinations, and brain specimens were taken. The changes in EEG in the other three groups were monitored at 2, 4 and 6 hours after LPS administration, and the α wave activity percentage was calculated. The blood was collected from abdominal aorta 6 hours after LPS administration, the rats were sacrificed and brain tissue was harvested. The concentrations of tumor necrosis factor-α (TNF-α) in plasma and brain were measured with enzyme-linked immunosorbent assay (ELISA). The histology and ultrastructure changes in the prefrontal cortex in the rats were observed with both light microscope and transmission electron microscope. Compared with sham group, the percentage of α wave on EEG was significantly increased at 2, 4 and 6 hours after LPS administration in model group [(14.52±0.50)%, (16.70±0.85)%, (17.35±0.36)% vs. (12.60±0.46)%, all P<0.01]. It could be deduced that early brain dysfunction occurred in septic rats. Compared with model group, percentage of α wave on EEG was significantly reduced at 2, 4, and 6 hours in VNS group [(13.10±0.24)% vs. (14.52±0.50)%, (12.81±0.53)% vs. (16.70±0.85)%, (12.61±0.37)% vs. (17.35±0.36)%, all P<0.01], while there was no such effect in the VGX group. Compared with sham group, the concentrations of TNF-α in plasma and brain were all increased in model group [ plasma TNF-α(ng/L): 120.11±5.10 vs. 24.37±1.85, brain TNF-α(ng/L): 165.20±6.31 vs. 14.89±0.83, both P<0.01]. Compared with model group, the concentrations of TNF-α in plasma and brain were all significantly decreased in VNS group [ plasma TNF-α(ng/L): 46.72±4.90 vs. 120.11±5.10, brain TNF-α(ng/L): 107.95±1.83 vs. 165.20±6.31, both P<0.01], while there was no such effect in the VGX group. Light microscope and transmission electron microscope showed that the damage of brain tissue and neurons in model group and VGX group was more obvious, while that in the VNS group was less severe, though not completely disappeared. LPS can lead to sepsis-associated encephalopathy in rats. It was shown that electrical stimulation of the vagus nerve can activate anti-inflammatory effect through cholinergic pathway, and improve the cerebral function, and inhibit the development of sepsis-associated encephalopathy by reducing systemic and cerebral inflammatory reaction.