Role of Arachidonic Acid Metabolic Dysregulation in Sheep Brain Injury Caused by Coenurus cerebralis Infection

BACKGROUND: Coenurus cerebralis (C. cerebralis) infection is a common parasitic disease in sheep that causes severe neurological damage. However, the underlying metabolic changes triggered by this pathogen in host sheep remain poorly understood. This study aimed to explore the effects of C. cerebralis infection on in vivo metabolic functions in sheep. METHODS: Broad-targeted blood metabolomics was used to screen differential serum metabolites between C. cerebralis-infected sheep (BE-P group) and healthy sheep (BE-N group). Combined with KEGG enrichment analysis and ELISA assays, we further validated key metabolic molecules and related pathways. RESULTS: A total of 25 significantly differential metabolites were identified, including 19 upregulated and 6 downregulated metabolites. KEGG enrichment indicated that the arachidonic acid (AA) metabolic pathway was the most significantly dysregulated pathway. ELISA results showed that serum phospholipids (PLs), phospholipase A2 (PLA2), AA, prostaglandin E2 (PGE2), thromboxane B2 (TXB2), 5-hydroxyeicosatetraenoic acid (5-HETE), leukotriene B4 (LTB4), cysteinyl leukotriene receptor 2 (CysLT2R), and soluble epoxide hydrolase (sEH) were markedly increased, whereas epoxy-eicosatrienoic acids (EETs) were decreased in the BE-P group. C. cerebralis infection disturbed the AA metabolic pathway, with abnormal activation of its downstream cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) branches. These changes were accompanied by neuroinflammation, oxidative stress and microcirculation disturbance, which ultimately disrupted cerebral metabolism. Notably, serum CysLT2R level in the BE-P group was 2.13-fold higher than that in the BE-N group, representing the most prominent difference. CysLT2R may mediate neuroinflammation, blood-brain barrier disruption and neuronal injury through the Gαq signaling pathway. CONCLUSIONS: C. cerebralis infection disturbs the arachidonic acid metabolic pathway and activates its downstream metabolic cascades. CysLT2R is a key altered molecule, which may participate in the brain injury induced by C. cerebralis infection.