Cortistatin deficiency reveals a dysfunctional brain endothelium with impaired gene pathways, exacerbated immune activation, and disrupted barrier integrity
Journal of Neuroinflammation · 12 authors, 5 centres
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Using cortistatin-deficient mice and human brain endothelial cells in an in vitro ischemia-like model, the authors found that lack of cortistatin predisposes the brain endothelium to barrier disruption, tight-junction breakdown, and dysregulated immune activity, while exogenous cortistatin treatment reversed these deleterious effects.
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This preclinical mechanistic study investigated the role of the neuropeptide cortistatin in brain endothelium integrity using cortistatin-deficient (Cort−/−) and wild-type murine brain endothelial cells, human brain endothelial cells, and an in vivo LPS-injection mouse model. The authors assessed endothelial permeability using tracers of different sizes, tight-junction integrity via immunofluorescence, inflammatory responses by qPCR and ELISA, and transcriptomic programming through RNA-sequencing. Cortistatin-deficient endothelial cells exhibited increased permeability, tight-junction protein redistribution (ZO-1, claudin-1, claudin-5, VE-cadherin), F-actin stress fiber formation, and dysregulated gene pathways under both basal and injured conditions. RNA-sequencing revealed impaired extracellular matrix remodelling, angiogenesis, and protective response pathways. Exogenous cortistatin reversed hyperpermeability, junction disruption, inflammatory response, and in vivo BBB leakage.
