Glial Contribution to the Pathogenesis of Post-Operative Delirium Revealed by Multi-omic Analysis of Brain Tissue from Neurosurgery Patients DOI Creative Commons

Takaya Ishii,

Tao Wang, Kazuki Shibata

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Post-operative delirium (POD) is a common complication after surgery especially in elderly patients, characterized by acute disturbances consciousness and cognition, which negatively impacts long-term outcomes. Effective treatments remain elusive due to the unclear pathophysiology of POD. To address knowledge gap, we investigated DNA methylation profiles gene expression changes brain cells from POD non-POD patients who underwent resection for medication refractory epilepsy. analysis revealed alteration epigenetic status immune inflammation-related genes. Single-nucleus RNA sequencing (snRNAseq) identified POD-specific glial cell alterations, particularly microglia, where neuroinflammation was strongly enhanced, consistent with findings. Astrocytes exhibited synapse-related functions migration. Furthermore, downstream indicated similarities between POD-associated states pathologies such as encephalitis dementia. Overall, this study-the first multi-omics tissue patients-provides direct evidence contributions pathogenesis, highlights potential therapeutic targets.

Language: Английский

Glial Contribution to the Pathogenesis of Post-Operative Delirium Revealed by Multi-omic Analysis of Brain Tissue from Neurosurgery Patients DOI Creative Commons

Takaya Ishii,

Tao Wang, Kazuki Shibata

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Post-operative delirium (POD) is a common complication after surgery especially in elderly patients, characterized by acute disturbances consciousness and cognition, which negatively impacts long-term outcomes. Effective treatments remain elusive due to the unclear pathophysiology of POD. To address knowledge gap, we investigated DNA methylation profiles gene expression changes brain cells from POD non-POD patients who underwent resection for medication refractory epilepsy. analysis revealed alteration epigenetic status immune inflammation-related genes. Single-nucleus RNA sequencing (snRNAseq) identified POD-specific glial cell alterations, particularly microglia, where neuroinflammation was strongly enhanced, consistent with findings. Astrocytes exhibited synapse-related functions migration. Furthermore, downstream indicated similarities between POD-associated states pathologies such as encephalitis dementia. Overall, this study-the first multi-omics tissue patients-provides direct evidence contributions pathogenesis, highlights potential therapeutic targets.

Language: Английский

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