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

  • Brain Res Bull. 2025 Dec 20:111693. doi: 10.1016/j.brainresbull.2025.111693.
Shuangkai Li  1 ,  Xiang Li Jr  1 ,  Lu Peng  2 ,  Haojie Ding  1 ,  Xuan Shi  1 ,  Jiale Liu  1 ,  Haiying Li  1 ,  Jianguo Xu  3 ,  Qing Sun  4
Affiliations
  • 1. Department of Neurosurgery, Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China.
  • 2. Xinqiao Hospital, The Second Affiliated Hospital of Army Medical University, Chongqing, 400038, China.
  • 3. Department of Neurosurgery, Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China. Electronic address: [email protected].
  • 4. Department of Neurosurgery, Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China; Institute of Stroke Research, Soochow University, Suzhou 215006, China. Electronic address: [email protected].
PMID: 41429330 DOI: 10.1016/j.brainresbull.2025.111693
Abstract

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.

Keywords
CAY10566; Ischemic stroke; Microglia; Neuroinflammation; SCD1.
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