Inhibition of SCD1 attenuates neuroinflammation and brain injury after cerebral ischemia-reperfusion.

Neuroinflammation mediated by microglial hyperactivation represents a pivotal pathological mechanism exacerbating neuronal damage following cerebral ischemia. Stearoyl-CoA desaturase 1 (SCD1), the rate-limiting enzyme in monounsaturated fatty acid synthesis, plays a crucial regulatory role in metabolic and inflammatory processes. However, its specific function in post-ischemic neuroinflammation remains incompletely understood. This study found that SCD1 was highly expressed in the penumbra region following middle cerebral artery occlusion/reperfusion (MCAO/R) in mice. Then, we systematically evaluated the role of SCD1 in regulating neuroinflammation after cerebral ischemia-reperfusion and explored its underlying mechanisms through administrating SCD1-specific inhibitor CAY10566. Results showed that CAY10566 significantly reduced level of pro-inflammatory cytokines and infarct volume after cerebral ischemia-reperfusion. Furthermore,suppression of SCD1 also alleviated neuronal apoptosis and improved cognitive and motor functions after ischemic stroke Mechanistically, the modulation of the NF-κB signaling pathway by SCD1 may involve the participation of TNFR1. Collectively, these findings suggested that the SCD1 may serve as a critical checkpoint regulating NF-κB signaling in cerebral ischemia-reperfusion injury. Targeting SCD1 may represent a promising therapeutic strategy for ischemic stroke.

• Publication year

  2025

• Venue

  Brain Research Bulletin

• Publication date

  2025-12-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.brainresbull.2025.111693PMID 41429330
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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