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<p>Cerebral ischemia-reperfusion (I/R) injury triggers a cascade of neuroinflammatory responses and multiple forms of regulated cell death. PANoptosis, integrating pyroptosis, apoptosis, and necroptosis, has been implicated in inflammatory disorders, but its role in cerebral I/R remains unclear. This study explored the molecular profile and immune relevance of PANoptosis-related genes (PRGs) in rat I/R injury.&#xa0;A rat I/R model was established by transient middle cerebral artery occlusion (MCAO). Transcriptome sequencing identified differentially expressed genes (DEGs) using DESeq2, and PANoptosis-related DEGs (PR-DEGs) were obtained by intersecting with GeneCards-derived PRGs. Functional enrichment (GO, KEGG, Metascape, GSEA), weighted gene co-expression network analysis (WGCNA), and immune infiltration analyses were performed to uncover biological functions and immune features associated with PR-DEGs.&#xa0;Rats subjected to I/R injury showed significant infarction, neurological deficits, and increased TNF-α, IL-1β, and IL-10 expression, along with downregulated Bcl-2 and upregulated CD16 and iNOS, indicating strong inflammatory responses. A total of 51 PR-DEGs were identified, primarily enriched in inflammatory and immune signaling pathways such as TNF, NF-κB, and MAPK. WGCNA revealed the salmon module as most correlated with I/R injury, and hub genes including CASP8, STAT3 were identified. Correlation and immune infiltration analyses demonstrated strong associations between key PR-DEGs and pro-inflammatory immune cells, suggesting a close relationship between PANoptosis-associated gene expression patterns and immune dysregulation in I/R injury.&#xa0;Our findings suggest coordinated activation of PANoptosis-related signaling in cerebral I/R injury. CASP8 and STAT3 were identified as key PR-DEGs associated with I/R, providing a foundation for further mechanistic investigation.</p> Graphic Abstract <p></p> <p>Transcriptomic profiling of the cerebral ischemia-reperfusion model identifies PANoptosis-related genes and reveals their role in driving inflammatory responses and immune dysregulation, highlighting PANoptosis as a key contributor to neuronal injury following ischemia-reperfusion.</p>

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Integrative Analysis Identifies PANoptosis-Associated Molecular Patterns and Immune Alterations in Rat Cerebral Ischemic-Reperfusion Injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月29日

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  • Lu Li,
  • Yu Wang,
  • Huili Li,
  • Ying Gao,
  • Lan Luo,
  • Sheng Wang,
  • Mu Jin

摘要

Cerebral ischemia-reperfusion (I/R) injury triggers a cascade of neuroinflammatory responses and multiple forms of regulated cell death. PANoptosis, integrating pyroptosis, apoptosis, and necroptosis, has been implicated in inflammatory disorders, but its role in cerebral I/R remains unclear. This study explored the molecular profile and immune relevance of PANoptosis-related genes (PRGs) in rat I/R injury. A rat I/R model was established by transient middle cerebral artery occlusion (MCAO). Transcriptome sequencing identified differentially expressed genes (DEGs) using DESeq2, and PANoptosis-related DEGs (PR-DEGs) were obtained by intersecting with GeneCards-derived PRGs. Functional enrichment (GO, KEGG, Metascape, GSEA), weighted gene co-expression network analysis (WGCNA), and immune infiltration analyses were performed to uncover biological functions and immune features associated with PR-DEGs. Rats subjected to I/R injury showed significant infarction, neurological deficits, and increased TNF-α, IL-1β, and IL-10 expression, along with downregulated Bcl-2 and upregulated CD16 and iNOS, indicating strong inflammatory responses. A total of 51 PR-DEGs were identified, primarily enriched in inflammatory and immune signaling pathways such as TNF, NF-κB, and MAPK. WGCNA revealed the salmon module as most correlated with I/R injury, and hub genes including CASP8, STAT3 were identified. Correlation and immune infiltration analyses demonstrated strong associations between key PR-DEGs and pro-inflammatory immune cells, suggesting a close relationship between PANoptosis-associated gene expression patterns and immune dysregulation in I/R injury. Our findings suggest coordinated activation of PANoptosis-related signaling in cerebral I/R injury. CASP8 and STAT3 were identified as key PR-DEGs associated with I/R, providing a foundation for further mechanistic investigation.

Graphic Abstract

Transcriptomic profiling of the cerebral ischemia-reperfusion model identifies PANoptosis-related genes and reveals their role in driving inflammatory responses and immune dysregulation, highlighting PANoptosis as a key contributor to neuronal injury following ischemia-reperfusion.