Summary Reason for performing study: Accumulations of mucus within the trachea are often found during endoscopic examinations of the airways of poorly performing racehorses, but the clinical importance of this finding is unknown. Objectives: To determine the effect of tracheal mucus, pharyngeal lymphoid hyperplasia (PLH) and cytological indices of tracheal aspirate on racing performance in Thoroughbred horses assessed by race place and whether the horse was raced. Methods: Endoscopic examination of the nasopharynx, larynx and trachea was performed, and a tracheal aspirate obtained monthly at Thistledown racetrack from April to December, 2002 and 2003. Horses received a score of 0–4 for the degree of PLH and 0–4 for the amount of mucus visible in the trachea. The tracheal aspirate was assessed for turbidity, and total and differential cell counts. Generalised estimating equations models were used as repeated measures models for each risk factor and the level of association assessed through the risk factor's P value in the model. Results: Moderate to severe tracheal mucus (2–4) was a risk factor for poor racing performance. There was no association between degree of PLH, cell counts or turbidity of tracheal wash fluid and racing performance. However, horses that raced had higher total neutrophil counts in tracheal wash aspirates than horses that did not race. Conclusions: Grades 2–4 tracheal mucus should be considered a potential cause of poor racing performance in Thoroughbred horses. Clinical relevance: Because moderate to severe tracheal mucus accumulation, and not increased tracheal neutrophils, was a risk factor for poor racing performance, functionally significant airway inflammation may best be confirmed by the presence of mucus rather than increased number of neutrophils in the trachea.

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Sepsis-associated encephalopathy (SAE) is a major and frequent complication in patients with sepsis resulting in delirium and premature death. Sepsis survivors commonly suffer from long-term cognitive impairment causing immense burden on patients, caregivers, and economic health systems. The underlying pathophysiology of SAE is largely unresolved, thus treatment options are missing. We report that experimental polymicrobial sepsis in mice induces synaptic pathology in the central nervous system underlying defective long-term potentiation and cognitive dysfunction. Analysis of differentially expressed genes revealed severely affected downregulation of genes related to neuronal and synaptic signaling in the brain, e.g. of the activity-regulated cytoskeleton-associated protein (Arc), of the transcription-regulatory EGR family, and of the dual-specificity phosphatase 6 (Dusp6). On the protein level, ARC expression and mitogen-activated protein (MAP) kinase signaling in the brain was disturbed during SAE. For targeted rescue of dysregulated synaptic signaling and plasticity, we overexpressed ARC in the hippocampus by bilateral in-vivo stereotactic microinjection of an adeno-associated virus containing a neuron-specific plasmid of the Arc transgene. Hereby, defective synaptic plasticity and signaling in the hippocampus were restored and memory function improved. Accordingly, synaptic plasticity, neuronal spine pathology, and memory dysfunction also improved when post-septic mice were subjected to enriched environment demonstrating the potential for activity-induced recovery of long-term cognitive dysfunction. Together, we identified synaptic pathology of neurocognitive dysfunction after severe systemic infection and provide a proof-of-concept approach to interfere with SAE pathomechanisms leading to cognitive improvement.

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