PET imaging of TSPO in a rat model of sepsis induced by peritoneal polymicrobial infection

Abstract

Abstract Background Sepsis is a life-threatening acute organ dysfunction secondary to infection that affects more than 30 million people worldwide. In the USA, 1.5 million people develop sepsis, and at least 250,000 Americans die from sepsis each year. After hospitalization, patients suffer from long-term impairments in memory, attention, verbal fluency, and executive functioning. The translocator protein (TSPO), marker of activated microglia astrocytes cells, can be measured in vivo using positron emission tomography (PET). Our working hypothesis is that systemic inflammation associated with sepsis activate microglia cells, which will later lead to further long-term cognitive impairment in sepsis survivors. Methods To test this hypothesis, adult male Wistar rats were subjected to a gold standard sepsis model induced by cecal ligation and perforation (CLP) surgery to induce peritoneal poly microbial sepsis or sham surgery as a control group. At 24 hour after the surgery the animals were subjected to translocator protein (TSPO) microPET imaging with [11C]PBR28. Following the imaging, TSPO, cytochrome C, cytokines/chemokines, microglia (Iba-1) and astrocyte marker (GFAP) were measured in the prefrontal cortex and hippocampus of the septic animals. Results septic animals presented and increased uptake of [11C]PBR28-microglia activation in the whole brain compared to control at 24 after the CLP surgery. The expression of IL-1α, IL-1β, IL-6, IL-18, TNF-α, IFN-γ and Iba-1 increased in the hippocampus of septic rat. Conclusion The upregulation of TSPO expression in the hippocampus of septic rat brain is a possible mechanism associated with long-term cognitive impairment in sepsis survivors.