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Sequential Transcriptome Changes in the Penumbra after Ischemic Stroke.

In-Ae Choi1, Ji Hee Yun1, Ji-Hye Kim1

  • 1Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea.

International Journal of Molecular Sciences
|January 1, 2020
PubMed
Summary

This study reveals dynamic gene expression changes after stroke, with early decreases in brain function pathways and later increases in inflammation and cell proliferation, offering new therapeutic targets for stroke recovery.

Keywords:
acute strokechronic strokegene profile alterationsischemic penumbrastroketranscriptome

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Area of Science:

  • Neuroscience
  • Genomics
  • Molecular Biology

Background:

  • Stroke induces complex molecular changes in the brain.
  • Understanding the temporal dynamics of gene expression post-stroke is crucial for identifying therapeutic targets.

Purpose of the Study:

  • To investigate time-dependent alterations in gene expression profiles during the acute-to-chronic phases following photothrombotic stroke.
  • To identify key biological pathways and protein-protein interactions (PPI) affected by stroke.

Main Methods:

  • Differential gene expression analysis between naive and peri-infarct cortical tissues at 1, 4, and 8 weeks post-stroke.
  • Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis.
  • Protein-protein interaction (PPI) network analysis using STRING database.

Main Results:

  • Identified 3771, 536, and 533 differentially expressed genes (DEGs) at 1, 4, and 8 weeks post-stroke, respectively.
  • Early (1 week) downregulation of genes involved in brain development, memory, and neurotransmitter signaling pathways (e.g., Dlg4, Bdnf, Gria1, Rhoa, Mapk8).
  • Later (4-8 weeks) upregulation of genes related to cell proliferation, adhesion, and inflammatory responses, with altered KEGG pathways including complement/coagulation cascades and immune responses (e.g., CD44, C1, Fcgr2b, Spp1, Cd74).

Conclusions:

  • Gene expression profiles exhibit distinct temporal shifts, reflecting the evolving pathophysiology of stroke.
  • These time-dependent molecular changes highlight specific biological processes and pathways that could be targeted for novel stroke therapies.