ArticleProceedings of the National Academy of Sciences of the United States of America2023
Molecular profiling of the stroke-induced alterations in the cerebral microvasculature reveals promising therapeutic candidates.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Surgical protocol and ischemic duration determine myeloid cell features and locomotor deficits in preclinical transient middle cerebral artery occlusion.Experimental neurology · 2026Article
- Knockdown of endothelial Serpine1 improves stroke recovery by attenuating peri-infarct blood flow and blood-brain barrier disruption.Cell death & disease · 2026Article
- Loss of angiopoietin-2 leads to region-specific brain malformations and blood-brain barrier leakage.JCI insight · 2026Article
- Predictor Role ofMedicina (Kaunas, Lithuania) · 2025Article
- Ceramides in cardiovascular disease: emerging role as independent risk predictors and novel therapeutic targets.Cardiovascular research · 2025Review
- Changing genes, cells and networks to reprogram the brain after stroke.Nature neuroscience · 2025Review
- The Complex Role of the miR-17-92 Cluster in Stroke: Mechanistic Insights and Biomarker Potential.Genes · 2025Review
- A molecular brain atlas reveals cellular shifts during the repair phase of stroke.Journal of neuroinflammation · 2025Article
- Unravelling the nexus of stroke and dementia: Deciphering the role of secondary neurodegeneration in orchestrating cognitive decline.Neuroprotection (Chichester, England) · 2025Review
- Comparative analysis of In vivo endothelial cell translatomes across central nervous system vascular beds.Experimental eye research · 2024Article
- Article
- Blood-brain barrier disruption: a culprit of cognitive decline?Fluids and barriers of the CNS · 2024Review
- Targeting lipid nanoparticles to the blood-brain barrier to ameliorate acute ischemic stroke.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Subventricular zone cytogenesis provides trophic support for neural repair in a mouse model of stroke.Nature communications · 2023Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Stroke-induced cerebral microvascular dysfunction contributes to aggravation of neuronal injury and compromises the efficacy of current reperfusion therapies. Understanding the molecular alterations in cerebral microvessels in stroke will provide original opportunities for scientific investigation of novel therapeutic strategies. Toward this goal, using a recently optimized method which minimizes cell activation and preserves endothelial cell interactions and RNA integrity, we conducted a genome-wide transcriptomic analysis of cerebral microvessels in a mouse model of stroke and compared these transcriptomic alterations with the ones observed in human, nonfatal, brain stroke lesions. Results from these unbiased comparative analyses have revealed the common alterations in mouse stroke microvessels and human stroke lesions and identified shared molecular features associated with vascular disease (e.g., Serpine1/Plasminogen Activator Inhibitor-1, Hemoxygenase-1), endothelial activation (e.g., Angiopoietin-2), and alterations in sphingolipid metabolism and signaling (e.g., Sphigosine-1-Phosphate Receptor 2). Sphingolipid profiling of mouse cerebral microvessels validated the transcript data and revealed the enrichment of sphingomyelin and sphingoid species in the cerebral microvasculature compared to brain and the stroke-induced increase in ceramide species. In summary, our study has identified novel molecular alterations in several microvessel-enriched, translationally relevant, and druggable targets, which are potent modulators of endothelial function. Our comparative analyses have revealed the presence of molecular features associated with cerebral microvascular dysfunction in human chronic stroke lesions. The results shared here provide a detailed resource for therapeutic discovery of candidates for neurovascular protection in stroke and potentially, other pathologies exhibiting cerebral microvascular dysfunction.
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