Role of C-X-C motif chemokine 13 in sepsis-associated encephalopathy in mice

Abstract

Objective To evaluate the role of C-X-C motif chemokine 13(CXCL13)in sepsis-associated encephalopathy in mice. Methods A total of 64 healthy male C57BL/6J mice, aged 3-4 months, weighing 20-25 g, were divided into 4 groups(n=16 each)using a random number table method: sham operation group(Sham group), sepsis group(S group), CXCL13 siRNA group(si-CXCL13 group)and negative control siRNA group(si-control group).5-bromo-2-deoxyuridine(BrdU)50 mg/kg was intraperitoneally injected twice a day for 3 consecutive days in the four groups, and then lipopolysaccharide 500 μg/kg was intraperitoneally injected to establish the sepsis model in S, si-CXCL13 and si-control groups.CXCL13 siRNA 5 μl and siRNA 5 μl were injected into the left lateral cerebral ventricle in si-CXCL13 and si-control groups, respectively, at 3 days before establishing the model.Morris water maze test was performed at 5 days after establishing the model.The escape latency, time spent in the target quadrant, and the number of crossing the platform were recorded.Mice were sacrificed after the end of test, brains were removed and hippocampi were isolated for examination of the pathological changes of the dentate gyrus(with a light microscope)and for determination of the expression of CXCL13, C-X-C motif chemokine receptor 5(CXCR5)and brain-derived neurotrophic factor(BDNF), and the number of BrdU and BrdU/NeuroD positive cells(by immunofluorescence). Results Compared with sham group, the escape latency was significantly prolonged, the time spent in the target quadrant was shortened, and the number of crossing the platform was reduced on 2nd-4th days, the number of BrdU positive cells in the dentate gyrus was increased, and the number of BrdU/NeuroD positive cells in the dentate gyrus was decreased in S, si-CXCL13 and si-control groups, and the expression of CXCL13 and CXCR5 was up-regulated, and the expression of BDNF was down-regulated in LPS and si-control groups(P 0.05). Conclusion CXCL13 is involved in sepsis-associated encephalopathy through regulating hippocampal neurogenesis, and the mechanism may be related to down-regulating the expression of hippocampal BDNF in mice. Key words: Sepsis; Brain; Chemokine CXCL13