Pyroptosis, a programmed inflammatory necrotizing cell death, is likely involved in spinal cord ischemia-reperfusion (SCI/R) injury, but the mechanisms initiating driving neuronal pyroptosis must be further revealed. The aim of this study is to unravel the mechanism of long non-coding RNA (lncRNA) H19 during SCI/R. SCI/R model was induced in C57BL/6 mice by blocking the aortic arch in vivo , and oxygen-glucose deprivation/reperfusion (OGD/R) injury model of PC12 cells was established in vitro . Our results showed that H19 and HMGB1 expression was upregulated, while miR-181a-5p was downregulated in the SCI/R mice and OGD/R-treated PC12 cells. SCI/R induced pathological damage, pyroptosis and inflammation compared with the sham group. H19 acted as a molecular sponge to suppress miR-181a-5p, and HMGB1 was identified as a direct target of miR-181a-5p. MiR-181a-5p overexpression inhibited the increase of IL-1β, IL-18 and TNF-α production and NLRP3, ASC, and Cleaved-caspase-1 expression in OGD/R-treated PC12 cells; while miR-181a-5p silencing exerted opposite effects. HMGB1 overexpression reversed H19 knockdown-mediated the inhibition of pyroptosis and inflammation in OGD/R-treated PC12 cells. In vivo , H19 knockdown promoted the hind limb motor function recovery and alleviated the pathological damage, pyroptosis and inflammation induced by SCI/R. LncRNA H19/miR-181a-5p/HMGB1 pathway contributes to pyroptosis via activating caspase1 signaling during SCI/R, suggesting that this axis may be a potent therapeutic target in SCI/R.

Purpose Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) concentration is increased in cerebrospinal fluid (CSF) in early symptomatic phase of Alzheimer’s disease (AD). This study investigated whether CSF sTREM2 has a relationship with early cognitive dysfunction following surgery in cardiac surgery patients. Methods A total of 82 patients undergoing thoracoabdominal aortic replacement were recruited in this study. Neuropsychological testing battery was conducted before and after surgery. Postoperative cognitive dysfunction (POCD) was defined as a Z-score > 1.96 on at least 2 different tests or Telephone Interviews for Cognitive Status-Modified (TICS-M) score < 27. The CSF and serum sTREM2, Aβ42, T-tau and P-tau were collected and measured by ELISA on day before surgery and postoperative day 3. Results Patients were classified into POCD (n = 34) and non-POCD (n = 48) groups according to Z-score. Compared to non-POCD group, the levels of CSF sTREM2 (p < 0.001) and serum sTREM2 (p = 0.001) were significantly higher in POCD group on postoperative day 3. The levels of Aβ42 (p = 0.005) and Aβ42/T-tau ratio (p = 0.036) were significantly lower in POCD group on postoperative day 3. Multivariate logistic regression analysis revealed that higher value of postoperative CSF sTREM2 (odds ratio: 1.06, 95% confidence interval: 1.02–1.11, p = 0.009), age (OR: 1.15, 95%CI: 1.03–1.28, p = 0.014) and POD duration (OR: 2.47, 95%CI: 1.15–5.29, p = 0.02) were the risk factors of POCD. Conclusion This study indicates that anesthesia and surgery-induced elevation of CSF sTREM2 is associated with an increased risk of early cognitive dysfunction following surgery.

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Purpose Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) concentration is increased in cerebrospinal fluid (CSF) in early symptomatic phase of Alzheimer’s disease (AD). This study investigated whether CSF sTREM2 has a relationship with postoperative cognitive dysfunction (POCD) in cardiac surgery patients. Methods A total of 82 patients undergoing thoracoabdominal aortic replacement were recruited in this study. Neuropsychological testing battery was conducted before and after surgery. POCD was defined as a Z-score > 1.96 on at least 2 different tests or Telephone Interviews for Cognitive Status-Modified (TICS-M) score < 27. The CSF and serum sTREM2, Aβ42, T-tau and P-tau were collected and measured by ELISA on day before surgery and postoperative day 3. Results Patients were classified into POCD (n = 34) and non-POCD (n = 48) groups according to Z-score. Compared to non-POCD group, the levels of CSF sTREM2 (p < 0.001) and serum sTREM2 (p = 0.001) were significantly higher in POCD group on postoperative day 3, the levels of Aβ42 (p = 0.005) and Aβ42/T-tau ratio (p = 0.036) were significantly lower in POCD group on postoperative day 3. Multivariate logistic regression analysis revealed that higher value of postoperative CSF sTREM2 (odds ratio: 1.06, 95% confidence interval: 1.02–1.11, p = 0.009), age (OR: 1.15, 95%CI: 1.03–1.28, p = 0.014) and POD duration (OR: 2.47, 95%CI: 1.15–5.29, p = 0.02) were the influencing factors of POCD. Conclusion This study indicates that elevated CSF sTREM2 is associated with an increased risk of early POCD.