Background

The original equine sepsis score provided a method of identifying foals with sepsis. New variables associated with sepsis have been evaluated, but the sepsis score has not been updated.

Objectives

To evaluate the sensitivity and specificity of 2 updated sepsis scores and the systemic inflammatory response syndrome (SIRS) criteria in regard to detecting sepsis in foals.

Animals

Two-hundred and seventy-three ill foals and 25 healthy control foals.

Methods

Historical, physical examination, and clinicopathologic findings were used to calculate the original sepsis score and 2 updated sepsis scores. SIRS criteria were also evaluated. Sepsis scores and positive SIRS scores were statistically compared to foals with sepsis.

Results

One-hundred and twenty-six foals were septic and 147 sick-nonseptic. The original and updated sepsis scores were significantly higher in septic foals as compared to sick-nonseptic and healthy foals. The sensitivity and specificity of the updated sepsis scores to predict sepsis were not significantly better than those of the original sepsis score. One-hundred and twenty-seven of 273 (46.5%) foals met the original SIRS criteria and 88/273 (32%) foals met the equine neonatal SIRS criteria. The original SIRS criteria had similar sensitivity and specificity for predicting sepsis as did the 3 sepsis scores in our study.

Conclusions and clinical importance

The updated sepsis scores did not provide improved ability in predicting sepsis. Fulfilling the original SIRS criteria provided similar sensitivity and specificity in predicting sepsis as the modified sepsis score and might serve as a diagnostic aid in identifying foals at risk for sepsis.

The neuronal mitochondrial metabolite N-acetylaspartate (NAA) is decreased in the multiple sclerosis (MS) brain. NAA is synthesized in neurons by the enzyme N-acetyltransferase-8-like (NAT8L) and broken down in oligodendrocytes by aspartoacylase (ASPA) into acetate and aspartate. We have hypothesized that NAA links the metabolism of axons with oligodendrocytes to support myelination. To test this hypothesis, we performed lipidomic analyses using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high-performance thin-layer chromatography (HPTLC) to identify changes in myelin lipid composition in postmortem MS brains and in NAT8L knockout (NAT8L^-/-) mice which do not synthesize NAA. We found reduced levels of sphingomyelin in MS normal appearing white matter that mirrored decreased levels of NAA. We also discovered decreases in the amounts of sphingomyelin and sulfatide lipids in the brains of NAT8L^-/- mice compared to controls. Metabolomic analysis of primary cultures of oligodendrocytes treated with NAA revealed increased levels of α-ketoglutarate, which has been reported to regulate histone demethylase activity. Consistent with this, NAA treatment resulted in alterations in the levels of histone H3 methylation, including H3K4me3, H3K9me2, and H3K9me3. The H3K4me3 histone mark regulates cellular energetics, metabolism, and growth, while H3K9me3 has been linked to alterations in transcriptional repression in developing oligodendrocytes. We also noted the NAA treatment was associated with increases in the expression of genes involved in sulfatide and sphingomyelin synthesis in cultured oligodendrocytes. This is the first report demonstrating that neuronal-derived NAA can signal to the oligodendrocyte nucleus. These data suggest that neuronal-derived NAA signals through epigenetic mechanisms in oligodendrocytes to support or maintain myelination.