Zinc provides neuroprotection by regulating NLRP3 inflammasome through autophagy and ubiquitination in a spinal contusion injury model

Abstract

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Zinc attenuates ferroptosis and promotes functional recovery in contusion spinal cord injury by activating Nrf2/GPX4 defense pathway

“…The changes in some central nervous system cells and related protein factors in the acute phase of spinal cord injury can effectively affect the pathological changes of spinal cord injury and promote wound healing. Anti‐inflammatory environment, the more anti‐inflammatory and antioxidant effects of zinc require further experiments to verify these conjectures and perfect the mechanism of action of zinc 26 . In general, it is clear that zinc is used as conventional antioxidants, and the clinical application of immune‐regulating trace elements provides a reliable theoretical basis and medication recommendations for protection against nerve injury.…”

“… 31 In previous studies, we found that zinc promotes the recovery of exercise behavior in mice with spinal cord injury. 16 , 26 , 28 , 32 , 33 Recently, ferroptosis was discovered to be involved in spinal cord injury, many oxidation products, and hemoglobin fragmentation 30 ; regrettably, the central nervous system is rich in unsaturated fatty acids, causing ferroptosis to play a pivotal role in the initial stage of injury. 34 , 35 …”

“…Artificial bladder massage was performed twice a day for urination during the first week after surgery and then once a day until the mice resumed urination on their own. Mice in the SCI + ZnG group and SCI + ZnG + Brusatol group were injected intraperitoneally with ZnG (Biotopped, China) or Brusatol (25 mg/mL; #SML1868, Sigma‐Aldrich, USA) at a dose of 30 mg/kg or 2 mg/kg in 0.1 mL vehicle [DMSO (D4540, Sigma‐Aldrich, USA) and 0.9% NaCl (MB2471, Meilunbio, China), 1:3] two hours after the successful establishment of the model and were injected once a day until the third day 25,26 . The mice in the SCI group were injected intraperitoneally with an equivalent dose of isotonic glucose in 0.1 mL vehicle (DMSO and 0.9% NaCl, 1:3) two hours after successful modeling.…”

Zinc Regulates Glucose Metabolism of the Spinal Cord and Neurons and Promotes Functional Recovery after Spinal Cord Injury through the AMPK Signaling Pathway

“…All animals were intraperitoneal anesthesia with 50 mg/kg pentobarbital sodium, and the model of SCI was established by the weight-drop method as we previously described [ 22 ]. Briefly, a laminectomy was performed at the T9-T10 level and moderate contusion injury was made by dropping an impactor (2 mm diameter, 12.5 g, 2 cm in height) onto the surface of the spinal cord.…”

“…Spinal cord tissues or cells were collected for WB assay as we described previously [ 22 ]. The following antibodies were used: anti-cleaved caspase 3 (1 : 1000, Affinity, USA), anti-Bax (1 : 1000, Affinity, USA), anti-Bcl-2 (1 : 1000, Affinity, USA), anti-PGC- α (1 : 1000, CST, USA), anti-NRF2 (1 : 1000, CST, USA), anti-p-AMPK (1 : 1000, CST, USA), anti-AMPK (1 : 1000, CST, USA), anti-GLUT4 (1 : 1000, Affinity, USA), anti-GLUT3 (1 : 1000, Affinity, USA), anti-HO-1 (1 : 1000, Affinity, USA), anti-NQO1 (1 : 1000, Affinity, USA), anti- β -actin (1 : 1000, Proteintech, USA), HRP-conjugated AffiniPure Goat Anti-Mouse IgG (1 : 10000, Proteintech, USA), and HRP-conjugated AffiniPure Goat Anti-Rabbit IgG (1 : 10000, Proteintech, USA).…”