Single-Cell Insights Into Cellular Response in Abdominal Aortic Occlusion-Induced Hippocampal Injury

Objective: Ischemia-reperfusion of the abdominal aorta often results in damage to distant organs, such as the heart and brain. This cellular heterogeneity within affected tissues complicates the roles of specific cell subsets in abdominal aorta occlusion model (AAO) injury. However, cell type-specific molecular pathology in the hippocampus after ischemia is poorly understood.

Aims: In this study, we adopted a mouse AAO to investigate the single-cell transcriptome in the hippocampi in AAO mice.

Methods: Male C57BL/6 mice (8 weeks old) were used to create an AAO model, with animals divided into Sham and I/R groups. The I/R group was subjected to 2 h of ischemia followed by 24 h of reperfusion, after which hippocampal tissues were collected for single-cell RNA sequencing and histological analysis. Behavioral tests, including the Rotarod, Y-maze, and new object recognition tests, were performed daily for 28 days post-surgery to evaluate neurological function. A total of 62,624 cells were corresponding 7 cell types with neuronal, glial, and vascular lineages. We next analyzed cell-specific gene alterations in AAO mice and the function of these cell-specific Genes.

Results: AAO injury upregulated astrocyte and oligodendrocyte precursor cell (OPC) proportions (p-value < 0.05). Astrocytes showed unique gene expression related to neurogenesis and mRNA processing. Five distinct astrocyte subtypes emerged post-injury. OPCs exhibited enhanced synapse organization. Microglia activation and the elevated expression level of the epithelial cell oxidative phosphorylation protein-protein interaction (PPI) module indicate an inflammatory response and metabolic changes in response to AAO injury.

Conclusions: Our scRNA-seq analysis provides insights into transcriptional changes at the single-cell level in response to AAO-induced hippocampal injury. This study illustrates how the hippocampal region responds to such injury and identifies potential therapeutic targets for intervention, thereby paving the way for future research and treatment strategies.