Association Between Sleep Quality and Postcolonoscopy Pain.

Acute infections from diverse sources are associated with significant post-infectious morbidity and mortality, although the underlying mechanisms remain largely unknown (; ). Severe infection can lead to a dysregulated immune response and organ dysfunction—a condition known as sepsis, which affects approximately 50 million individuals globally each year (). Survivors of sepsis often experience prolonged neuropsychiatric symptoms, including anxiety, depression, and cognitive impairment (; ). The public health burden of sepsis survivorship means there is an urgent need to understand the mechanisms of this post-sepsis syndrome and to develop targeted treatments. Rodent infection survivors exhibit behavioral changes reminiscent of human post-sepsis and post-infectious syndromes, including increased anxiety-like behavior, impaired extinction of conditioned fear, and impairments on other hippocampal-dependent cognitive tasks (; ; ; ; ; ). Use of these rodent models has pointed to persistent neuroinflammation as a key potential driver of these post-infectious behaviors. In our previous work, we showed upregulation of pro-inflammatory genes in the hippocampus of male and female murine infection survivors, with lipocalin-2 () as the most highly upregulated target (). LCN2 is a pleiotropic cytokine with previously identified roles in kidney disease, cancer, infection, and neuroinflammation (; ; ; ; ; ). It is part of the acute phase response, with LCN2 levels being acutely upregulated in blood, brain, and liver following turpentine administration, lipopolysaccharide (LPS) endotoxin injection, and cecal ligation and puncture (CLP) (; ; ; ; ). It binds bacterial and mammalian siderophores and exerts antimicrobial properties in part via its iron-sequestering capability (; ; ). Prior work suggested that LCN2 can exert a pro- or anti-inflammatory role in the brain depending on the context. In some cases, -null mice showed exacerbated neuroinflammation, increased mortality, and increased levels of serum transaminases and lactate dehydrogenase after administration of 2, 5, and 20 mg/kg of LPS, which suggests an important anti-inflammatory role for LCN2 even in the absence of a live bacterial infection (; ). However, in other studies, knockout either had no effect on neuroinflammation when a lower dose of LPS was used or mitigated glial activation and neuroinflammation after a 5 mg/kg LPS challenge, which is more consistent with a pro-inflammatory role (; ). Furthermore, various groups have shown that -null mice exhibit anxiety-like behaviors, altered hippocampal activity, and impaired dendritic arborization compared to wild-type controls (; ; ). These findings led us to hypothesize that LCN2 might be an important regulator of neuroinflammation and behavior in infection survivors.