The incidence of central nervous system (CNS) disease has persistently increased over the last several years. There is an urgent need for effective methods to improve the cure rates of CNS disease. However, the precise molecular basis underlying the development and progression of major CNS diseases remains elusive. A complete molecular map will contribute to research on CNS disease treatment strategies. Emerging technologies such as single-cell RNA sequencing (scRNA-seq) and Spatial Transcriptomics (ST) are potent tools for exploring the molecular complexity, cell heterogeneity, and functional specificity of CNS disease. scRNA-seq and ST can provide insights into the disease at cellular and spatial transcription levels. This review presents a survey of scRNA-seq and ST studies on CNS diseases, such as chronic neurodegenerative diseases, acute CNS injuries, and others. These studies offer novel perspectives in treating and diagnosing CNS diseases by discovering new cell types or subtypes associated with the disease, proposing new pathophysiological mechanisms, uncovering novel therapeutic targets, and identifying putative biomarkers. Graphical Abstract Implications of scRNA-seq and ST for CNS diseases. A comprehensive understanding of cellular information and spatial context using scRNA-seq and ST, helping to elucidate the biological functions, the intricate connection between crucial regulatory pathways, and cell communication after CNS diseases.

Background:Stroke is a major cause of morbidity and mortality, characterized by neuronal damage and complex cell death pathways. This study aimed to investigate the protective role of spermine oxidase (Smox) in ischemic stroke and its effect on neuronal autophagy.Methods:We employed transient middle cerebral artery occlusion (tMCAO) models and oxygen-glucose deprivation/reoxygenation (OGD/R) experiments in HT22 cells to explore the protective effects of Smox knockdown against ischemic injury and to evaluate changes in autophagy.Results:Smox levels were significantly elevated following stroke, and correlated with increased autophagic activity and neuronal apoptosis. In contrast, knockdown of Smox reduced neuronal death and improved neurological function while decreasing autophagy activation. Mechanistically, Smox may regulate autophagy via the phosphorylation of protein kinase B (AKT), AMP-activated protein kinase (AMPK), and mechanistic target of rapamycin (mTOR); Smox knockdown increased AKT and mTOR phosphorylation, while reducing AMPK phosphorylation, suggesting a potential shift in the regulation of neuronal autophagy.Conclusions:Our findings suggest a dual role for Smox in stroke pathology, indicating that it may influence autophagy via the AKT/AMPK/mTOR signaling, which could be critical for neuronal survival after ischemic injury. Targeting Smox may offer a therapeutic strategy for neuronal protection and recovery in stroke management, suggesting the potential importance of autophagy modulation in ischemic brain injury.