An integrated liver, hippocampus and serum metabolomics based on UPLC-Q-TOF-MS revealed the therapeutical mechanism of Ziziphi Spinosae Semen in p-chlorophenylalanine-induced insomnia rats.

Ziziphi Spinosae Semen (ZSS), a well-known herbal medicine for treating insomnia, is popular in not only China but also in Europe, India and Iran. However, its underlying mechanisms remain unclear. In this work, taking the targeted organs of insomnia, the liver and hippocampus, as the objects, a combination metabolomics based on ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was established to illustrate the abnormality of metabolic characteristics of the liver, hippocampus and serum of p-chlorophenylalanine (PCPA)-induced insomnia rats and to demonstrate the mechanism of ZSS in treating insomnia. The results showed that ZSS could restore the brain cell morphology, decrease the degree of hepatocyte necrosis and regulate the disturbance of neurotransmitters and hormones in insomnia rats. In terms of metabolomics, a total of 33 liver metabolites, 25 hippocampal metabolites and 18 serum metabolites were finally selected as the potential biomarkers and an important pathway of phenylalanine, tyrosine and tryptophan biosynthesis was common in three tissues in PCPA rats. Meanwhile, ZSS significantly reversed the levels of 23 liver metabolites, 15 hippocampal metabolites and 5 serum metabolites. The present study demonstrates the actions of ZSS in treating insomnia by enhancing both cerebral and hepatic functions.

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

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.

Efficacy and mechanism of stellate ganglion block in patients undergoing carotid endarterectomy.

OBJECTIVES: Carotid endarterectomy (CEA) is an effective technique for carotid artery stenosis and has been widely used. Stellate ganglion block (SGB) has good effect on the treatment of both painful and non-painful diseases. To investigate the efficacy of SGB in terms of cerebral protection in patients undergoing CEA and to analyze its mechanism. METHODS: In this retrospective analysis, 120 patients who underwent CEA were enrolled and divided into study group (SG) (60 cases, general anesthesia and SGB) and control group (CG) (60 cases, general anesthesia). The differences in hemodynamic indexes, middle cerebral artery (MCA) hemodynamic indexes, and endocrine-related indexes between the two groups at the baseline, after induction of anesthesia (induction), and skin incision (incision) were compared. The differences in neurological function and pain level between two groups 1 day pre-operatively (pre-op 1), 1 day postoperatively (POD 1), 2 day postoperatively (POD 2), and 7 day postoperatively (POD 7) were also evaluated. Perioperative adverse events and intraoperative anesthetics dosage were compared between two groups. RESULTS: The systolic blood pressure, diastolic blood pressure, mean pulse pressure difference, and heart rate of SG at incision were lower than those of the CG (p < 0.05); Vs, Vd, and Vm of MCA were significantly higher in the SG than in CG at induction and incision (p < 0.05). Cortisol and aldosterone levels were lower and potassium and insulin levels were higher in the SG than in CG at induction and incision (p < 0.05); At pre-op 1, POD 1, POD 2, and POD 7, the VAS scores of patients in the SG were significantly lower than those in CG at POD 1, POD 2, and POD 7 (p < 0.05). The patients in SG showed decreased incidence of perioperative adverse events compared with the CG (p < 0.05); The consumption of anesthetics in the SG was lower than that in CG (p < 0.05). CONCLUSION: SGB in patients undergoing CEA treatment can improve perioperative cerebral blood supply and reduce the consumption of anesthetics and the incidence of perioperative adverse events, which is safe and feasible as a cerebral protection measure. Meanwhile, SGB may also help stabilize patients' perioperative hemodynamic indexes, but the result still needs to be supported by further large sample data.