Stellate ganglion block suppresses hippocampal ferroptosis to attenuate cerebral ischemia-reperfusion injury via the Hippo pathway.

Abstract

Ischemic stroke is a disabling and fatal disease caused by the insufficient blood supply to the brain. Stellate ganglion block (SGB) is a type of anesthesia commonly used to relieve pain. Here, we sought to identify the effects of SGB on cerebral ischemia-reperfusion (I/R) injury. The middle cerebral artery occlusion (MCAO) model was established in rats. The brain injury was assessed using the 2,3,5-triphenyl-tetrazolium-chloride (TTC) staining assay and neurological score. Ferroptosis was analyzed by detecting cell death, Fe2+ content, glutathione (GSH), malonic dialdehyde (MDA), superoxide dismutase (SOD), and ferroptosis-related factors. The mechanisms of SGB were assessed using the western blot. The results showed that I/R increased brain infarction and damaged neurological function. SGB decreased I/R-induced infarction and improved neurological function. Meantime, SGB inhibited ferroptosis of the hippocampus induced by I/R via the Hippo pathway. and the Yes1 associated transcriptional regulator (YAP) of this pathway was positively correlated with the ferroptosis-related solute carrier family 7 member 11 (SLC7A11). Inhibition of the Hippo pathway reversed the effects of SGB on brain injury and ferroptosis. In conclusion, SGB inhibited ferroptosis of hippocampal neurons via activating the Hippo pathway and thereby alleviated I/R injury. The data provide a novel insight into the treatment of ischemic stroke and even other ischemic encephalopathies.