stroke-related-animal-models-methodologies-applications-translational

Stroke-Related Animal Models: Methodologies, Applications, and Translational Perspectives

Stroke remains a leading cause of death and disability worldwide. Despite hundreds of neuroprotective agents showing promise in preclinical studies, ...

The Second Affiliated Hospital of Kunming Medical University

Multiple cell death pathways are involved in neuronal death in ischemic stroke (IS). However, the role of different cell death pathways in different cell types has not been elucidated. By analyzing three single-nucleus RNA sequencing (snRNA-seq) data of IS, we first found that a variety of programmed cell death (PCD) -related genes were significantly changed in different cell types. Based on machine learning and virtual gene knockout, we found that ferroptosis related genes, ferritin heavy chain 1 (Fth1) and ferritin light chain (Ftl1), play a key role in IS. Ftl1 and Fth1 can promote microglia activation, as well as the production of inflammatory factors and chemokines. Cell communication analysis showed that activated microglia could enhance chemotactic peripheral leukocyte infiltration, such as macrophages and neutrophils, through Spp1-Cd44 and App-Cd74 signaling, thereby aggravating brain tissue damage. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) showed that P2ry12 and Mef2c were significantly decreased in oxygen-glucose deprivation (OGD) group, while Ftl1, Fth1, Apoe, Ctsb, Cd44 and Cd74 were significantly increased in OGD group. Collectively, our findings suggested targeted therapy against microglia Ftl1 and Fth1 might improve the state of microglia, reduce the infiltration of peripheral immune cells and tissue inflammation, and then improve the ischemic brain injury in mouse.

Single-nucleus transcriptome unveils the role of ferroptosis in ischemic stroke.

Depression is a common mental health issue that can lead to various physical and psychological diseases. However, the relationship between depressive symptoms and premature death remains unclear.

Association between depressive symptoms and premature death: An exploratory mediation analysis via mitochondrial function.

The aim of this study is to analyze and identify genes associated with neuronal regeneration after ischemic stroke (IS) and to predict potential therapeutic targets for neuronal regeneration after IS using bioinformatics analysis methods.

Analysis and Identification of Therapeutic Targets for Neuronal Regeneration After Ischemic Stroke.

Ischemic stroke (IS) is a severe disease. The altered activation states of microglia play important roles in IS. In present study, a total of 125 C57BL/6 mice was used (N = 6 per group). Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD) were performed for in vivo and in vitro model construction. The infarct size was detected using TTC staining. The nerve injury was evaluated by a neurological deficit score. OGD-treated brain microvascular endothelial cells (BMECs) were co-cultured with BV2 cells. Cell viability was determined by CCK-8 assay, and the apoptosis rate was identified by flow cytometry analysis. Transendothelial electronic resistance (TEER) of the cells was measured by TEER measurement. Molecular interactions were analyzed using dual-luciferase reporter gene, ChIP, and Co-IP assays. All in vitro experiments were conducted with three replicates, and each experiment was performed in triplicate. We found that Src Homology 2B Adaptor Protein 3 (SH2B3) was overexpressed in the cerebral cortex tissues of MCAO treated mice (P < 0.01), and BMECs co-cultured with BV-2 cells under OGD conditions (P < 0.01). SH2B3 knockdown or Myocyte Enhancer Factor 2 A (MEF2A) overexpression reduced infarct size and improved neurological function in MCAO mice. SH2B3 knockdown enhanced OGD-treated cell viability (P < 0.05), inhibited cell apoptosis (P < 0.05) in BMECs, and ameliorated BBB (P < 0.01). Moreover, SH2B3 knockdown changed the activation status of microglia. MEF2A promoted the transcriptional activation of WW Domain Containing E3 Ubiquitin Protein Ligase 2 (WWP2) and WWP2 promoted the ubiquitination and degradation of SH2B3. SH2B3 overexpression reversed the effects of MEF2A overexpression on microglia states, BMECs injury and BBB function. In summary, MEF2A promoted the ubiquitination-mediated degradation of SH2B3 via transcription up-regulating WWP2, then changed the activation status of microglia, thus ameliorating BMEC injury, and finally ameliorating IS injury.

The Ubiquitination and Degradation of SH2B3 Mediated by MEF2A/WWP2 Axis Restores Microglial Homeostasis to Alleviate Cerebral Microvascular Endothelial Cell Injury in Ischemic Stroke.

Mental health is a major global concern, yet findings remain fragmented across studies and databases, hindering integrative understanding and clinical translation. To address this gap, we present the Mental Disorders Knowledge Graph (MDKG)-a large-scale, contextualized knowledge graph built using large language models to unify evidence from biomedical literature and curated databases. MDKG comprises over 10 million relations, including nearly 1 million novel associations absent from existing resources. By structurally encoding contextual features such as conditionality, demographic factors, and co-occurring clinical attributes, the graph enables more nuanced interpretation and rapid expert validation, reducing evaluation time by up to 70%. Applied to predictive modeling in the UK Biobank, MDKG-enhanced representations yielded significant gains in predictive performance across multiple mental disorders. As a scalable and semantically enriched resource, MDKG offers a powerful foundation for accelerating psychiatric research and enabling interpretable, data-driven clinical insights.

Large language model powered knowledge graph construction for mental health exploration.

Glioblastoma (GBM) remains a lethal brain cancer with median survival of 12-15 months, hindered by pronounced heterogeneity. Integrating histopathological, molecular, and microenvironmental data is critical for improving outcomes.

Article	Year
Single-nucleus transcriptome unveils the role of ferroptosis in ischemic stroke. Heliyon\| PubMed ID: 38994078	2024
Association between depressive symptoms and premature death: An exploratory mediation analysis via mitochondrial function. Journal of affective disorders\| PubMed ID: 39892752	2025
Analysis and Identification of Therapeutic Targets for Neuronal Regeneration After Ischemic Stroke. Brain and behavior\| PubMed ID: 40320842	2025
The Ubiquitination and Degradation of SH2B3 Mediated by MEF2A/WWP2 Axis Restores Microglial Homeostasis to Alleviate Cerebral Microvascular Endothelial Cell Injury in Ischemic Stroke. Neurochemical research\| PubMed ID: 40407948	2025
Large language model powered knowledge graph construction for mental health exploration. Nature communications\| PubMed ID: 40804250	2025
Integrating computational pathology and multi-transcriptomics to characterize glioblastoma heterogeneity and identify prognostic biomarkers. Human pathology\| PubMed ID: 41232838	2025

Chenglong Shi

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