ArticleJournal of neuroinflammation2023
Cortistatin deficiency reveals a dysfunctional brain endothelium with impaired gene pathways, exacerbated immune activation, and disrupted barrier integrity.
Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Cortistatin as a pleiotropic regulator of neuroimmune and inflammatory pathways in experimental disease: a scoping review of preclinical evidence.Inflammopharmacology · 2026Article
- Cortistatin as a modulator of inflammatory and mitochondrial dysfunction in Huntington´s disease.Journal of neuroinflammation · 2026Article
- Lack of cortistatin drives neuroimmune and vascular dysfunction in brain ischemia.Journal of biomedical science · 2026Article
- A systematic review and meta-analysis of the relationship between neuroinflammation and blood-brain barrier based onBiochemistry and biophysics reports · 2026Review
- Convergent molecular signatures across eating disorders and obsessive-compulsive disorder in the human brain.medRxiv : the preprint server for health sciences · 2024Article
- Blood-brain barrier disruption: a culprit of cognitive decline?Fluids and barriers of the CNS · 2024Review
- Cortistatin as a Novel Multimodal Therapy for the Treatment of Parkinson's Disease.International journal of molecular sciences · 2024Article
- Peptide discovery across the spectrum of neuroinflammation; microglia and astrocyte phenotypical targeting, mediation, and mechanistic understanding.Frontiers in molecular neuroscience · 2024Review
- Nanoarchitectonics of Injectable Biomimetic Conjugates for Cartilage Protection and Therapy Based on Degenerative Osteoarthritis Progression.Biomaterials research · 2024Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundBrain activity governing cognition and behaviour depends on the fine-tuned microenvironment provided by a tightly controlled blood-brain barrier (BBB). Brain endothelium dysfunction is a hallmark of BBB breakdown in most neurodegenerative/neuroinflammatory disorders. Therefore, the identification of new endogenous molecules involved in endothelial cell disruption is essential to better understand BBB dynamics. Cortistatin is a neuroimmune mediator with anti-inflammatory and neuroprotective properties that exerts beneficial effects on the peripheral endothelium. However, its role in the healthy and injured brain endothelium remains to be evaluated. Herein, this study aimed to investigate the potential function of endogenous and therapeutic cortistatin in regulating brain endothelium dysfunction in a neuroinflammatory/neurodegenerative environment.
methodsWild-type and cortistatin-deficient murine brain endothelium and human cells were used for an in vitro barrier model, where a simulated ischemia-like environment was mimicked. Endothelial permeability, junction integrity, and immune response in the presence and absence of cortistatin were evaluated using different size tracers, immunofluorescence labelling, qPCR, and ELISA. Cortistatin molecular mechanisms underlying brain endothelium dynamics were assessed by RNA-sequencing analysis. Cortistatin role in BBB leakage was evaluated in adult mice injected with LPS.
resultsThe endogenous lack of cortistatin predisposes endothelium weakening with increased permeability, tight-junctions breakdown, and dysregulated immune activity. We demonstrated that both damaged and uninjured brain endothelial cells isolated from cortistatin-deficient mice, present a dysregulated and/or deactivated genetic programming. These pathways, related to basic physiology but also crucial for the repair after damage (e.g., extracellular matrix remodelling, angiogenesis, response to oxygen, signalling, and metabolites transport), are dysfunctional and make brain endothelial barrier lacking cortistatin non-responsive to any further injury. Treatment with cortistatin reversed in vitro hyperpermeability, tight-junctions disruption, inflammatory response, and reduced in vivo BBB leakage.
conclusionsThe neuropeptide cortistatin has a key role in the physiology of the cerebral microvasculature and its presence is crucial to develop a canonical balanced response to damage. The reparative effects of cortistatin in the brain endothelium were accompanied by the modulation of the immune function and the rescue of barrier integrity. Cortistatin-based therapies could emerge as a novel pleiotropic strategy to ameliorate neuroinflammatory/neurodegenerative disorders with disrupted BBB.
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