Iwuchukwu I, Nguyen D, Shirazian A, Asatryan A, Jun B, Bazan NG
Abstract
Little is known of the lipid anti-inflammatory mediators, docosanoids, in intracerebral hemorrhage (ICH). We aim to characterize the abundance of the docosanoid, Neuroprotectin D1 (NPD1), in ICH patients.Blood samples (whole blood in PAXgene-blood-RNA tubes and plasma) were collected from consecutive patients with acute spontaneous ICH within 48 h of admission. A liquid-liquid lipid extraction was used for liquid chromatography-mass spectrometry (LC-MS/MS) and analyzed using MassLynx Mass Spectrometry Software with results normalized to internal standards. RNA was extracted from PAXgene-blood-RNA tubes for 15-LOX-1 gene expression, a critical enzyme in NPD1 synthesis. Demographic and clinical data were collected. Outcome measures included 90-day modified-rankin-score.Sixteen patients were included in the study with a mean age of 62.5years (SD13.5). Three abundant isomers were detected and analyzed - NPD1, PDX, and an uncharacterized isomer designated as NPD1-C. NPD1 levels were higher in patients with 90-day MRS 0-3 (49.63pg/mL SD43.78 vs. 1.88pg/mL SD1.7 p = 0.0012). ROC-AUC analysis showed an NPD1 cutoff of 2.9pg/mL differentiated 90-day MRS 0-3 (sensitivity 100%, specificity 88.89%, AUC 0.98 p = 0.0002). A Spearman correlation demonstrated an inverse relationship with NPD1 and 90-day MRS (rho -7.392 p = 0.0011). 15-LOX-1 gene was almost undetectable in patients with MRS 4-6. Though not significant, NPD1 levels were higher in patients <65 years, ICH volume <30 ml, and non-whites. NPD1 was abundant and significantly higher in ICH patients with MRS 0-3.15-LOX-1 was significantly under-expressed in patients with MRS 4-6. Early synthesis and abundance of NPD1 is likely an important protective mediator in ICH pathophysiology. (c) 2022 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.