Reduced phosphatidylcholine and phosphatidylethanolamine levels correlate with inflammatory activation in sepsis-associated encephalopathy

Sepsis-associated encephalopathy (SAE) is a severe complication of sepsis, often leading to poor neurological outcomes. Lipid molecules are increasingly recognized for their potential involvement in both sepsis and cognitive impairment. However, the relationship between lipidomic alterations and SAE remains incompletely understood. This study aims to investigate lipidomic changes in patients with SAE and explore potential associations between lipid metabolism and the development of SAE. Sepsis patients without pre-existing central nervous system disorders were prospectively enrolled. SAE was defined as a positive result on the Confusion Assessment Method for the ICU (CAM-ICU) or a Glasgow Coma Scale (GCS) score < 15. Blood samples were collected at enrollment and upon any change in cognitive status. Cerebrospinal fluid (CSF) samples were collected based on the physician assessment. Lipid metabolites were analyzed using high-performance liquid chromatography coupled with mass spectrometry. A total of 98 sepsis patients were enrolled, with 39 classified into the SAE group and 59 into the non-SAE group. Plasma levels of phosphatidylethanolamines (PE) and phosphatidylcholines (PC) were significantly decreased in SAE patients. Among these, LPC (18:2), LPC (16:0), LPE (22:6), and LPE (20:4) showed the most notable reductions. Additionally, 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) levels were decreased in SAE patients, while proinflammatory cytokines such as IFN-γ, IL-1ra, MCP-1, and IP-10 were elevated. Reduced levels of PC and PE lipids in SAE patients may reflect underlying inflammatory processes. The observed downregulation of HMG-CoA and upregulation of IP-10 and MCP-1 suggest a potential therapeutic role for statins in the management of SAE. Clinical Trial Registry number and website where it was obtained: Clinical Trial NCT04230447 (Registration Date: 01/02/2021; https://www. gov/study/NCT04230447?cond=Sepsis%20Associated%20Encephalopathy&rank=4 ).