ArticlebioRxiv : the preprint server for biology2025
Tie2-Dependent Mechanisms Promote Leptomeningeal Collateral Remodeling and Reperfusion Following Stroke.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Leptomeningeal collaterals are distal pial arterial anastomotic vessels that provide an alternative route for redistributing cerebral blood flow following arterial obstruction, thereby limiting tissue damage. However, the regulatory mechanisms and strategies to enhance this adaptive response remain under investigation. This study explored the pharmacological effects of Tie2 receptor activation, using the peptide agonist Vasculotide, following permanent middle cerebral artery occlusion (pMCAO). Vasculotide improved collateral growth and remodeling, which correlated with reduced infarct volume, enhanced blood flow, and functional recovery within 24hrs post-pMCAO. In contrast, collateral growth was attenuated in Tie2 and EphA4/Tie2 double knockdown mice, while the loss of EphA4 increased Tie2 and Ang-1 expression and mimicked the positive effects of Vasculotide following stroke. Furthermore, bulk RNA sequencing of meningeal tissue identified key transcriptomic changes, including alterations in AJ-associated transcripts, such as
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