Shared transcriptomic signatures in perilesional and contralesional cortex after ischemic stroke

Area of Science:

• Neuroscience
• Molecular Biology
• Genomics

Background:

• Stroke recovery involves plasticity in both ipsilesional and contralesional cortex.
• Transcriptional studies often overlook the contralesional cortex (CLC), despite its remodeling.
• Sex-dependent differences in post-stroke responses are not fully understood.

Purpose of the Study:

• To investigate transcriptional responses in the peri-lesional cortex (PLC) and CLC after stroke.
• To determine if molecular responses in the CLC mirror those in the PLC.
• To explore potential sex differences in these responses.

Main Methods:

• Bulk RNA-sequencing of PLC and CLC in male and female mice 7 days post-stroke.
• Analysis of transcriptional profiles in regions near and remote from the infarct.
• Assessment of axonal sprouting at 6 weeks post-stroke.

Main Results:

• Both PLC and CLC showed significant upregulation of inflammatory signaling pathways.
• Shared transcriptional signatures, including reactive microglial genes, were observed in both regions.
• Neuroinflammatory responses were largely conserved between sexes, with comparable axonal sprouting.

Conclusions:

• The contralesional cortex exhibits a shared neuroinflammatory transcriptional response with the peri-lesional cortex post-stroke.
• This shared response is a key early feature of cortical plasticity during stroke recovery.
• The findings suggest conserved molecular mechanisms for repair across sexes.