Sepsis associated encephalopathy, occurs in 70% of severe septic cases, following which survivors exhibit long-term cognitive impairment or global loss of cognitive function. Currently there is no clearly defined neurochemical basis of septic encephalopathy. Moreover, the lingering neurological complications associated with the severe acute respiratory syndrome CoV 2 (SARS-CoV-2) and the significant worsening in outcomes for those individuals with SARS-Cov-2 following sepsis underscore the need to define factors underlying the susceptibility to acute toxic encephalitis. In this study, differential neurochemical sequelae in response to sepsis (lipopolysaccharide (LPS)-induced endotoxemia and caecal ligation and puncture (CLP)), were evaluated in two inbred mouse strains, known to differ in behaviour, immune profile, and neurotransmitter levels, namely BALB/c and C57BL/6J. It was hypothesized that these strains would differ in sepsis severity, cytokine profile, peripheral tryptophan metabolism and central monoamine turnover. BALB/c mice exhibited more pronounced sickness behavioural scores, hypothermia, and significant upregulation of cytokines in the LPS model relative to C57BL/6J mice. Increased plasma kynurenine/tryptophan ratio, hippocampal serotonin and brainstem dopamine turnover were evident in both strains, but the magnitude was greater in BALB/c mice. In addition, CLP significantly enhanced kynurenine levels and hippocampal serotonergic and dopaminergic neurotransmission in C57BL/6J mice. Overall, these studies depict consistent changes in kynurenine, serotonin, and dopamine post sepsis. Further evaluation of these monoamines in the context of septic encephalopathy and cognitive decline is warranted. Moreover, these data suggest the continued evaluation of altered peripheral kynurenine metabolism as a potential blood-based biomarker of sepsis.

脓毒症相关脑病发生在 70% 的严重脓毒症病例中，随后幸存者表现出长期认知障碍或整体认知功能丧失。目前，脓毒性脑病尚无明确的神经化学基础。此外，与严重急性呼吸综合征 CoV 2 (SARS-CoV-2) 相关的挥之不去的神经系统并发症，以及脓毒症后 SARS-Cov-2 患者的预后显着恶化，都强调需要确定急性呼吸综合征易感性的潜在因素。中毒性脑炎。在这项研究中，在两种近交小鼠品系中评估了脓毒症（脂多糖（LPS）诱导的内毒素血症和盲肠结扎穿刺（CLP））引起的不同神经化学后遗症，已知这两种近交小鼠品系在行为、免疫特征和神经递质水平方面存在差异。即BALB/c和C57BL/6J。假设这些菌株在脓毒症严重程度、细胞因子谱、外周色氨酸代谢和中枢单胺周转方面存在差异。相对于 C57BL/6J 小鼠，BALB/c 小鼠在 LPS 模型中表现出更明显的疾病行为评分、体温过低和细胞因子的显着上调。两种品系小鼠的血浆犬尿氨酸/色氨酸比率、海马血清素和脑干多巴胺周转率均明显增加，但 BALB/c 小鼠的幅度更大。此外，CLP 显着增强了 C57BL/6J 小鼠的犬尿氨酸水平以及海马血清素能和多巴胺能神经传递。总体而言，这些研究描绘了脓毒症后犬尿氨酸、血清素和多巴胺的一致变化。有必要在脓毒性脑病和认知能力下降的背景下对这些单胺进行进一步评估。此外，这些数据表明，持续评估外周犬尿氨酸代谢的改变作为败血症的潜在血液生物标志物。