Prognostic Role of Cuproptosis-Related Gene after Intracerebral Hemorrhage in Mice.

Abstract

Intracerebral hemorrhage (ICH) is a highly fatal form of stroke for which there are limited effective treatments. Cuproptosis, a newly discovered type of programmed cell death, has not yet been investigated in relation to ICH. Thus, the main goal of our study was to investigate the involvement of cuproptosis-related genes (CRGs) in predicting the early outcomes of ICH. We used datasets GSE228222 and GSE200575 from the Gene Expression Omnibus (GEO) database to identify and analyze differentially expressed genes (DEGs) between ICH samples and control samples from mice. From this analysis, seven cuproptosis-related DEGs (CuDEGs) were identified: pyruvate dehydrogenase E1 component subunit alpha (Pdha1), glutaminase (Gls), dihydrolipoamide dehydrogenase (Dld), pyruvate dehydrogenase E1 component subunit beta (Pdhb), dihydrolipoamide S-acetyltransferase (Dlat), metal regulatory transcription factor 1(Mtf1), and solute carrier family 31 member 1 (Slc31a1). Pathway enrichment analysis connected these genes to metabolic pathways, while immune cell infiltration analysis revealed increased macrophages and naive CD8 T cells alongside reduced NK resting cells and CD4 T cells in ICH samples. Verification through qRT-PCR and immunohistochemistry demonstrated a lower expression of CuDEGs in ICH samples. Of particular note, Gls, a gene significantly linked to both cuproptosis and immune regulation, exhibited reduced expression, possibly reflecting a protective response to limit glutamate production and mitigate neuronal damage. In summary, Gls emerges as a promising target for improving ICH outcomes by regulating cuproptosis and immune activity. This research provides novel insights into the molecular processes involved in ICH and suggests potential therapeutic approaches.