Our results for markers of neuronal ischemic injury and rate of recovery suggest that a clinical trial with sufficient statistical power to detect an effect of RIPC on the incidence of neurologic complications (paresis, palsy, etc) due to spinal cord ischemia-reperfusion injury after spine surgery is warranted [corrected].
The purpose of the present study was to examine the effects of myricetin on reducing cerebral ischemia injury in a rat model. A rat model of permanent middle cerebral artery occlusion (pMCAO) was used in the present study. Rats were randomized into the following five groups: Sham, model, low‑myricetin (1 mg/kg), medium‑myricetin (5 mg/kg) and high‑myricetin (25 mg/kg) groups. Neurological deficit scores were evaluated by an examiner blinded to the experimental groups. Brain infarct size was estimated macroscopically using 2,3,5‑triphenyltetrazolium chloride staining. The levels of inflammatory factors tumor necrosis factor (TNF)‑α, interleukin (IL)‑6 and IL‑1β, and oxidative stress index superoxide dismutase (SOD), malondiadehyde (MDA), and the glutathione/glutathione disulfide (GSH/GSSG) ratio were measured by ELISA. The degree of brain cell apoptosis was determined using a terminal deoxynucleotidyl transferase dUTP nick‑end labeling assay. Protein expression levels of total or phosphorylated p38 mitogen activated protein kinase (MAPK), nuclear factor (NF)‑κB/p65 and protein kinase B (AKT) were determined using a western blotting assay. The neurological deficit score and infarct area induced by pMCAO decreased in a dose‑dependent manner following myricetin treatment. Furthermore, myricetin reduced the expression levels of IL‑1β, IL‑6, TNF‑α, and MDA, and increased GSH/GSSG ratio and SOD activity. A significant decrease in cell apoptosis was observed in response to myricetin. In addition, myricetin significantly increased the level of phosphorylated AKT protein, and decreased the phosphorylation of p38 MAPK and the level of NF‑κB/p65. Overall, the results of the present study suggested that myricetin exhibits a therapeutic effect by reducing ischemic cerebral injury, and the protective effect of myricetin may be associated with the p38 MAPK, NF‑κB/p65 and AKT signaling pathways.
Background
Postoperative cognitive dysfunction (POCD) is associated with worsened prognosis especially in aged population. Clinical and animal studies suggested that electroacupuncture (EA) could improve POCD. However, the underlying mechanisms especially EA’s regulatory role of inflammasomes remain unclear.
Methods
The model of POCD was established by partial hepatectomy surgery in 18‐month mice with or without postoperative EA treatment to the Baihui acupoint (GV20) for 7 days. Cognitive functions were assessed by Morris water maze test, and proinflammatory cytokines IL‐1β and IL‐6 and microglia activity were assayed by qPCR, ELISA, or immunohistochemistry. Tight junction proteins, NLRP3 inflammasome and downstream proteins, and NF‐κB pathway proteins were evaluated by western blotting.
Results
EA markedly preserved cognitive dysfunctions in POCD mice, associated with the inhibition of neuroinflammation as evidenced by reduced microglial activation and decreased IL‐1β and IL‐6 levels in brain tissue. EA also preserved hippocampal neurons and tight junction proteins ZO‐1 and claudin 5. Mechanistically, the activation of NLRP3 inflammasome and NF‐κB was inhibited by EA, while NLRP3 activation abolished EA’s treatment effects on cognitive function.
Conclusion
EA alleviates POCD‐mediated cognitive dysfunction associated with ameliorated neuroinflammation. Mechanistically, EA’s treatment effects are dependent on NLRP3 inhibition.
This case confirms that metallic stenting may represent an effective treatment for anastomotic colonic strictures in the absence of other therapeutic alternatives.
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