Quantitative Profiling of Oxylipins in Acute Experimental Intracerebral Hemorrhage

Abstract

Oxylipins are a series of bioactive lipid metabolites derived from polyunsaturated fatty acids that are involved in cerebral homeostasis and the development of intracerebral hemorrhage (ICH). However, comprehensive quantification of the oxylipin profile in ICH remains unknown. Therefore, an ICH mouse model was constructed and liquid chromatography tandem mass spectrometry was then performed to quantify the change in oxylipins in ICH. The expression of the oxylipin relative enzymes was also reanalyzed based on RNA-seq data from our constructed ICH dataset. A total of 58 oxylipins were quantifiable and the levels of 17 oxylipins increased while none decreased significantly in the first 3 days following ICH. The most commonly increased oxylipins in ICH were derived from AA (10/17) and EPA (4/17) followed by LA (2/17) and DHA (1/17). 18-HEPE from EPA was the only oxylipin that remained significantly increased from 0.5 to 3 days following ICH. Furthermore, 14 of the increased oxylipins reached a peak level on the first day of ICH, and soon decreased while five oxylipins (PGJ2, 15-oxo-ETE, 12-HEPE, 18-HEPE, and 5-oxo-ETE) had increased 3 days after ICH suggesting that the profile shifted with the progression of ICH. In our constructed RNA-seq dataset based on ICH rats, 90 oxylipin relative molecules were detected except for COX. Among these, Cyp4f18, Cyp1b1, Cyp2d3, Cyp2e1, Cyp1a1, ALOX5AP, and PLA2g4a were found up-regulated and Cyp26b1 was found to decrease in ICH. In addition, there was no significant change in sEH in ICH. This study provides fundamental data on the profile of oxylipins and their enzymes in ICH. We found that the profile shifted as the progression of ICH and the metabolism of arachidonic acid and eicosapentaenoic acid was highly affected in ICH, which will help further studies explore the functions of oxylipins in ICH.

Age-related changes after intracerebral hemorrhage: a comparative proteomics analysis of perihematomal tissue

“…In contrast, lipid metabolism was significantly affected in the young mice. Oxylipin profiling at 12 h, 24 h, and 72 h after ICH in adult mouse brains was explored in a recent study, and the number of changed oxylipins was the highest on the first day of ICH [ 10 ]. In the present study, the expression of the apolipoprotein A-I (Apoa1) protein differed between young and aged ICH model mice, being significantly elevated exclusively in young mice.…”

“…A proteomics analysis detected differentially expressed proteins (DEPs) in plasma among young, middle-aged, and older healthy individuals and confirmed that insulin-like growth factor 1 is a promising novel approach for ameliorating aging-associated acute brain injury after ICH [ 9 ]. The other transcriptomic analysis distinguished the expression pattern of oxylipin enzymes between middle-aged and aged rats 3 days after experimental ICH induction and revealed that among the specific differentially expressed genes (DEGs), Cyp1a1 and Cyp2e1 were the most significant DEGs in the two age groups [ 10 ]. In addition, in pathological findings of animals with ICH, more severe brain swelling was observed in aged animals than in young animals, and aged animals exhibited different glial responses from young animals, impaired lesion resolution, and neuronal death [ 11 ].…”

The use of multiple datasets to identify autophagy-related molecular mechanisms in intracerebral hemorrhage

“…The GSE24265 Series Matrix File was downloaded from the GEO public database, noted by the GPL570 annotation file, of which the expression profile data belonged to 11 samples, including the perihematomal areas, gray matters, and white matters of 7 patients in the healthy control group and 4 patients with ICH ( Rosell et al, 2011 ). The GSE149317 Series Matrix File (only used to verify the expression level of key genes) was downloaded from the GEO public database, and the annotated File is GPL24688 ( Yuan et al, 2020 ). The microarray data included 6 cases in the healthy control group and 6 patients in the ICH group.…”

Integrating Contemporary Technologies in Education: Empowering Youth for Sustainable Future through New Literacies

“…Browsing, searching, and filtering data, information and digital content (1) Interacting through digital technologies (4) Developing digital content (10) Protecting devices (14) Solving technological problems (18) Evaluating data, information and digital content (2) Sharing through digital technologies (5) Integrating and reelaborating digital content (11) Protecting personal data and privacy (15) Identifying needs and technological responses (19) Managing data, information and digital content (3) Engaging in citizenship through digital technologies (6) Copyright and licenses (12) Protecting health and well-being (16) Creatively using digital technologies (20) Collaborating through digital technologies (7) Programming (13) Protecting the environment (17) Identifying digital competence gaps (21) Netiquette (8) Managing digital identity (9) *Specific knowledge, skills and attitudes are numbered to show the results in Table 11.…”