Post-stroke depression (PSD) is a common but severe mental complication after stroke. However, the cellular and molecular understanding of PSD is still yet to be illustrated. In current study, we prepared PSD rat model (MD) via unilateral middle cerebral artery occlusion (MCAO) and chronic stress stimulation (DEPR), and isolated hippocampal tissues for single cell sequencing of 10x Genomics Chromium. First, we determined the presence of the increased cell population of endothelium and microglia and the compromised oligodendrocytes in MD compared to NC, MCAO and DEPR. The enriched functions of highly variable genes (HVGs) of endothelium and microglia suggested a reinforced blood-brain barrier in MD. Next, cell clusters of endothelium, microglia and oligodendrocytes were individually analyzed, and the subtypes with distinct functions were identified. The presence of expression profiles, intercellular communications and signaling pathways of these three cell populations of PSD displayed a similar but more aggressive appearance with DEPR compared to MCAO and NC. Taken together, this study characterized the specific gene profile of endothelium, microglia and oligodendrocytes of hippocampal PSD by single cell sequencing, emphasizing the crosstalk among them to provide theoretical basis for the in-depth mechanism research and drug therapy of PSD.

Poststroke depression (PSD) is a common neuropsychiatric complication following stroke. Clinically, it is characterized by persistent low mood, cognitive dysfunction, and somatic symptoms, which severely impact the recovery and quality of life of stroke patients, making it an urgent issue in clinical practice. Currently, the pathogenesis of PSD remains incompletely understood. This study presents a narrative review of the literature from PubMed, Web of Science, and CNKI, with a particular focus on research conducted between 2021 and 2025. The findings reveal that advancements in neuroscience, immunology, and gut microbiome studies have contributed to important breakthroughs in understanding the mechanisms underlying PSD, such as the interaction between the hypothalamic–pituitary–adrenal (HPA) axis and neuroinflammation. In terms of treatment, several novel approaches have emerged. Traditional Chinese medicine (TCM) has attracted increasing attention due to its low cost, high safety, and minimal side effects. Herbal formulas have shown promising therapeutic effects for PSD. Moreover, combination therapies, such as acupuncture combined with repetitive transcranial magnetic stimulation (rTMS), have been demonstrated to be more effective than monotherapies. This review summarizes the multidimensional pathophysiology of PSD, including neurotransmitter imbalance, neuroinflammation, impaired neuroplasticity, structural brain damage, HPA axis dysregulation, gut-brain axis imbalance, and psychosocial factors. Additionally, current clinical treatment strategies for PSD are reviewed, with the aim of providing a theoretical foundation for early diagnosis, timely intervention, the development of novel anti-PSD therapies, and the establishment of more comprehensive treatment strategies for PSD.

Post-stroke depression (PSD) is a common but severe mental complication after stroke. However, the cellular and molecular understanding of PSD is still yet to be illustrated. In current study, we prepared PSD rat model (MD) via unilateral middle cerebral artery occlusion (MCAO) and chronic stress stimulation (DEPR), and isolated hippocampal tissues for single cell sequencing of 10x Genomics Chromium. First, we determined the presence of the increased cell population of endothelium and microglia and the compromised oligodendrocytes in MD compared to NC, MCAO and DEPR. The enriched functions of highly variable genes (HVGs) of endothelium and microglia suggested a reinforced blood-brain barrier in MD. Next, cell clusters of endothelium, microglia and oligodendrocytes were individually analyzed, and the subtypes with distinct functions were identified. The genotype of PSD displayed more similarity with DEPR compared to MCAO and NC. For endothelium, the absence of cell differentiation, but robust proliferation and fibrosis instead were observed in MD. For microglia, multiple subpopulations showed the superimposition of neurotoxic and neuroprotective functions, and DEPR could enlarge the effect of microglia in MCAO. For oligodendrocytes, the one for demyelination were elevated in DEPR and MD, while the one for remyelination were robust in MCAO, and the oligodendrocytes undergoing demyelination were processed via apoptosis, autophagy and ferroptosis manner. Finally, we also observed that the intercellular crosstalk among these three cells were largely elevated in MACO but compromised in DEPR, whereas was intermediate between them in MD, and depression and stroke could both activate the inflammation reaction but through different signals. Taken together, this study characterized the single cell expression profile of hippocampal PSD, and unmask the differential expressed genes of endothelium, microglia and oligodendrocytes, emphasizing the crosstalk among them to provide theoretical basis for the in-depth mechanism research and drug therapy of PSD.