ArticleCNS neuroscience & therapeutics2026
Orexin B Reduces Cerebral Aneurysms Through Inhibition of SP-1.
Article in CNS neuroscience & therapeutics, 2026. 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
backgroundCerebral aneurysms (CAs) are pathological dilations of intracranial arteries with high rupture risk, yet the molecular mechanisms driving their formation remain incompletely understood. The Orexin B/OX2R system, known for regulating arousal and metabolism, has recently been implicated in vascular pathology, but its role in CAs has not been explored.
methodsSerum Orexin A and B levels were measured in 38 CA patients and 43 healthy controls. A murine CA model (elastase-induced) was established using wild-type (WT) and OX2R knockout (OX2R
resultsCA patients and mice exhibited significantly reduced serum Orexin B levels (CA patients: 3.21 ± 0.52 vs. controls: 8.56 ± 1.23 pg/mL, p < 0.01), with no change in Orexin A. OX2R expression was downregulated in the circle of Willis of CA mice. Orexin B administration attenuated aneurysm formation in WT mice (size reduction from 3.72 ± 0.469 mm to 1.93 ± 0.252 mm, p < 0.01) but not in OX2R
conclusionsThe Orexin B/OX2R axis is dysregulated in CAs, and Orexin B protects against CA formation through OX2R-dependent anti-inflammatory mechanisms involving SP-1 suppression. These findings identify the Orexin B/OX2R/SP-1 pathway as a potential therapeutic target for cerebral aneurysms.
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