Integrated Multi-Omics Identifies Core Molecular Targets in Cerebral Venous Sinus Thrombosis-Induced Brain Injury

Area of Science:

• Neuroscience
• Molecular Biology
• Bioinformatics

Background:

• Cerebral venous sinus thrombosis (CVST) causes significant brain injury and intracranial hypertension.
• The molecular mechanisms underlying CVST remain poorly understood, hindering targeted therapy development.
• This study addresses the need for comprehensive molecular insights into CVST-induced brain lesions.

Purpose of the Study:

• To systematically identify key molecular targets and signaling pathways in CVST-induced brain injury.
• To utilize multi-omics approaches for a detailed molecular landscape analysis.
• To explore potential therapeutic targets and compounds for CVST treatment.

Main Methods:

• Established an optimized rat model of cerebral venous sinus thrombosis (CVST).
• Employed transcriptomic, proteomic, and single-cell RNA sequencing on cortical tissues.
• Conducted comprehensive bioinformatics analyses, including network construction, molecular docking, and molecular dynamics simulations.

Main Results:

• Identified 12 core genes (e.g., CD44, JAK2, CASP3) and associated pathways in immune response and tissue repair.
• Single-cell sequencing confirmed gene expression and cell-type specificity.
• Molecular docking suggested glucocorticoids (dexamethasone, methylprednisolone) bind effectively to JAK2, PTGS2, and CD44; methylprednisolone showed stable complex formation with CD44.

Conclusions:

• Integrated multi-omics profiling provides a systematic molecular map of CVST-induced brain injury.
• Identified novel candidate targets and signaling pathways offer a basis for further research.
• Potential therapeutic compounds, including glucocorticoids, warrant further investigation for CVST treatment.