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Shared Transcriptomic Signatures in Perilesional and Contralesional Cortex.

Dene Betz1,2, Victoria A Alers1,2, Matthew Kenwood1,2

  • 1Department of Neurology, Long School of Medicine, UT Health San Antonio, San Antonio, Texas, USA.

Biorxiv : the Preprint Server for Biology
|February 12, 2026
PubMed
Summary
This summary is machine-generated.

Stroke triggers brain plasticity for recovery. Both peri-lesional and contralesional cortices show similar inflammatory responses, driven by microglia, impacting stroke recovery in male and female mice.

Keywords:
axonal sproutingcontralesional cortexmicrogliaperilesional cortexpost-stroke plasticitysex-differences in strokestrokestroke recovery

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genomics

Background:

  • Stroke induces a critical period of heightened brain plasticity, crucial for functional recovery.
  • Post-stroke plasticity involves mechanisms in both ipsilesional and contralesional cortex.
  • Previous gene expression studies primarily focused on the infarct core and peri-lesional cortex (PLC).

Purpose of the Study:

  • To investigate the transcriptional response of the contralesional cortex (CLC) to stroke.
  • To compare molecular pathways in the PLC and CLC, particularly across sexes.
  • To understand the role of microglia in early post-stroke cortical plasticity.

Main Methods:

  • Bulk RNA sequencing of PLC and CLC in male and female mice at 7 days post-stroke.
  • Gene Ontology enrichment analysis to identify activated biological pathways.
  • Assessment of CLC-derived corticospinal tract axonal sprouting at 6 weeks post-stroke.

Main Results:

  • Both PLC and CLC exhibited robust upregulation of inflammatory signaling pathways, including cytokine signaling, leukocyte activation, and gliogenesis.
  • Reactive microglia signaling was identified as the dominant shared pathway in both regions.
  • The CLC did not display a distinct transcriptional response compared to the PLC.
  • No significant sex differences were observed in the transcriptional response or axonal sprouting.

Conclusions:

  • Stroke induces a shared, microglia-centered neuroinflammatory transcriptional response in both the peri-lesional and contralesional cortex.
  • Microglial reactivity is a key early process contributing to post-stroke cortical plasticity.
  • These findings are consistent across male and female mice, suggesting conserved mechanisms.