Severe inflammation in new-borns induces long-term cognitive impairment by activation of IL-1ß/KCC2 signaling during early development.

BACKGROUND: Neonatal sepsis can induce long-term cognitive impairment in adolescence or adulthood, but the underlying molecular mechanism is not fully understood. The expression of K+-Cl- co-transporter 2 (KCC2) plays a pivotal role in the GABAergic shift from depolarizing to hyperpolarizing during early postnatal development. In this study, we aimed to determine whether neonatal severe inflammation-induced cognitive impairment was associated with the expression of KCC2 during early development. METHODS: Neonatal severe inflammation was established by intraperitoneal injection of high dose lipopolysaccharide (LPS, 1 mg kg-1) in postnatal day 3 (P3) rats. The Morris water maze task and fear conditioning test were used to investigate long-term cognitive functions. ELISA, RT-PCR and Western blotting were used to examine the expression levels of proinflammatory cytokines and KCC2. Perforated patch-clamping recordings were used to determine the GABAergic shift. RESULTS: Neonatal severe inflammation led to long-term cognitive impairment in rats. Meanwhile, sustained elevation of interleukin-1 beta (IL-1ß) levels was found in the hippocampus until P30 after LPS injection. Elevated expression of KCC2 and hyperpolarized GABA reversal potential (EGABA) were observed in CA1 hippocampal pyramidal neurons from the P7-P10 and P14-P16 rats after LPS injection. Specific knockdown of IL-1ß mRNA expression rescued the elevated expression of KCC2 and the hyperpolarized EGABA at P7-P10 and P14-P16. Accordingly, specific knockdown of IL-1ß or KCC2 expression improved the cognitive impairment induced by neonatal severe inflammation. CONCLUSIONS: Sustained elevation of IL-1ß in the hippocampus may induce cognitive impairment by upregulation of KCC2 during early development.

Effect of Scalp Nerve Block with Ropivacaine on Postoperative Pain in Patients Undergoing Craniotomy: A Randomized, Double Blinded Study.

Scalp nerve block with ropivacaine has been shown to provide perioperative analgesia. However, the best concentration of ropivacaine is still unknown for optimal analgesic effects. We performed a prospective study to evaluate the effects of scalp nerve block with varied concentration of ropivacaine on postoperative pain and intraoperative hemodynamic variables in patients undergoing craniotomy under general anesthesia. Eighty-five patients were randomly assigned to receive scalp block with either 0.2% ropivacaine, 0.33% ropivacaine, 0.5% ropivacaine, or normal saline. Intraoperative hemodynamics and post-operative pain scores at 2, 4, 6, 24 hours postoperatively were recorded. We found that scalp blockage with 0.2% and 0.33% ropivacaine provided adequate postoperative pain relief up to 2 h, while administration of 0.5% ropivacaine had a longer duration of action (up to 4 hour after craniotomy). Scalp nerve block with varied concentration of ropivacaine blunted the increase of mean arterial pressure in response to noxious stimuli during incision, drilling, and sawing skull bone. 0.2% and 0.5% ropivacaine decreased heart rate response to incision and drilling. We concluded that scalp block using 0.5% ropivacaine obtain preferable postoperative analgesia compared to lower concentrations. And scalp block with ropivacaine also reduced hemodynamic fluctuations in craniotomy operations.

Survival analysis of intraoperative blood salvage for patients with malignancy disease: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Intraoperative blood salvage as a blood-saving strategy has been widely used in surgery. Considering its theoretic risk of malignant tumor cells being reinfused and the corresponding blood metastases, the safety of intraoperative blood salvage in cancer surgery remains controversial. METHODS: Following the Preferred Reporting Items for Systemic Review and Meta-Analysis (PRISMA), we searched the Cochrane Library, MEDLINE and EMBASE to November 2017. We included only studies comparing intraoperative blood salvage with allogeneic blood transfusion. RESULTS: This meta-analysis included 9 studies with 4354 patients with 1346 patients in the intraoperative blood salvage group and 3008 patients in the allogeneic blood transfusion group. There were no significant differences in the 5-year overall survival outcome (odds ratio [OR] 1.12; 95% confidence interval [CI], 0.80-1.58), 5-year disease-free survival outcome (OR 1.08; 95% CI 0.86-1.35), or 5-year recurrence rate (OR 0.86; 95% CI 0.71-1.05) between the 2 study groups. Subgroup analysis also showed no significant differences in the 5-year overall survival outcome (OR 0.97; 95% CI 0.57-1.67) of hepatocellular carcinoma patients in liver transplantation. CONCLUSIONS: For patients with malignant disease, intraoperative blood salvage did not increase the tumor recurrence rate and had comparable survival outcomes with allogeneic blood transfusion.