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To investigate the mechanism dexmedetomidine in relieving the neurotoxicity of a developing brain induced by sevoflurane. Sprague-Dawley rats, 6 days old, were randomly divided into three groups. Rats in the control group were inhaled with air after injection of normal saline; rats in the sevoflurane group were injected with normal saline and inhaled with 3% sevoflurane for 2 h in three consecutive day; rats in the dexmedetomidine group were inhaled with 3% sevoflurane after intraperitoneal injection of dexmedetomidine 25 μg/kg. WB results showed that mBDNF, pTrkB/TrkB, and CREB were significantly decreased in the hippocampus of the sevoflurane group, which are significantly upregulated in the dexmedetomidine group. In the sevoflurane group, proBDNF, P75NRT, and RhoA were significantly increased, which were significantly lower than those in the dexmedetomidine group than those in the sevoflurane group. The expression BDNF was downregulated in the sevoflurane group, while the proBDNF was upregulated in the sevoflurane group. In the Morris water maze test, the escape latency of the sevoflurane group was significantly prolonged. In sevoflurane groups, the number of crossing platform was significantly reduced, the synaptic protein decreased significantly, and this effect was reversed in rats of the dexmedetomidine group. Dexmedetomidine could reduce synaptic plasticity decline in developing rats induced by sevoflurane, through downregulating the proBDNF-p75NTR-RhoA pathway and upregulating BDNF-TrkB-CREB. [ABSTRACT FROM AUTHOR]

Background: About 2% of pregnant women receive non-obstetric surgery under general anesthesia each year. During pregnancy, general anesthetics may affect brain development of the fetus. This study aimed to investigate safe dosage range of isoflurane. Methods: Forty-eight SpragueDawley (SD) pregnant rats were randomly divided into 3 groups and inhaled 1.3% isoflurane (the Iso1 group), 2.0% isoflurane (the Iso2 group) and 50% O2 alone (the control group) for 3 h, respectively. Their offsprings were subjected to Morris water maze at day 28 and day 90 after birth to evaluate learning and memory. The expression of cAMP-response element binding protein (CREB) and phosphorylated cAMP-response element binding protein (p-CREB) was detected in the hippocampus dentate gyrus. Results: Less offsprings of Iso2 group were able to cross the platform than that of the control group (P < 0.05). Accordingly, the Iso2 offsprings expressed p-CREB mainly in the subgranular zone in contrast to the whole granular cell layer of hippocampus dentate gyrus as detected in the Iso1 and control offsprings; the expression level of pCREB was also lower in the Iso2 than Iso1 or control offsprings (P < 0.05). Conclusion: Inhalation of isoflurane at 1.3% during pregnancy has no significant influence on learning and memory of the offspring; exposure to isoflurane at 2.0% causes damage to spatial memory associated with inhibition of CREB phosphorylation in the granular cell layer of hippocampus dentate gyrus. [ABSTRACT FROM AUTHOR]

As a general anesthetic widely used in surgical, sevoflurane has been shown to cause cognitive and memory deficits in the elderly. It's important to find out agents that can counteract sevoflurane-induced cognitive dysfunction. This study is aimed to investigate the effect of lovastatin on sevoflurane-induced cognitive impairment in aged rats and reveal the potential mechanisms. BV-2 cells, rat hippocampal neurons or male aged rats were exposed to 2% sevoflurane for 5 h. The cells were pretreated with 10 μM lovastatin. The rats were intraperitoneally injected with 5 mg/kg/day lovastatin for three days. The results showed that lovastatin enhanced exosomal IDE secretion from sevoflurane-exposed BV-2 cells and promoted Aβ degradation. Lovastatin treatment also inhibited the increased expressions of β-secretase 1 (BACE1) and γ-secretase in hippocampal neurons under sevoflurane exposure in vitro. In animal experiments, the discrimination index in novel object recognition test and percentage of spontaneous alternation in Y-maze test were significantly elevated after lovastatin administration. In addition, Aβ plaque area and contents of soluble Aβ 1-40 and Aβ 1-42 in the hippocampal tissues were decreased upon lovastatin treatment. Furthermore, lovastatin reversed sevoflurane-induced Aβ accumulation via up-regulating IDE expression, and down-regulating amyloid precursor protein (APP)-related protein expression (β-C-terminal fragment (CTF), BACE1 and γ-secretase). In conclusion, lovastatin alleviates sevoflurane-induced cognitive deficient in aged rats via promoting Aβ degradation and reducing Aβ production. Lovastatin may be beneficial in preventing anesthetic-induced cognitive impairment. • Lovastatin promoted Aβ degradation in vitro and in vivo. • Lovastatin improved sevoflurane-induced cognitive disorder. • Lovastatin increased IDE secretion from BV-2 cells via an exosome secretory pathway. [ABSTRACT FROM AUTHOR]

• Maternal sevoflurane exposure in pregnancy affected Ngb expression in neonatal rats. • Hemin inhibited the decline of Ngb caused by sevoflurane in offspring rats. • Ngb over expression inhibited the endogenous apoptosis induced by sevoflurane. • Elevated Ngb increased Hif-1α expression. • Ngb over expression improved the long-term learning and memory of offspring rats. As a general anesthesia drug, sevoflurane has been found to be potentially neurotoxic to the developing brain. Neuroglobin (Ngb) is a novel oxygen-carrying globulin that has been demonstrated to have neuroprotective effects in a variety of central nervous system disorders. However, it is unclear whether Ngb has a protective effect on nerve damage caused by sevoflurane. Therefore, this study was designed to investigate the effect and related mechanisms of Ngb on neural injury induced by sevoflurane. Pregnant rats on gestational day 20 (G20) were exposed to 3.5% sevoflurane for two hours, which led to an increase of Ngb on the 0-1st day after birth and decreased significantly on the 3rd day, while Cytochrome c increased from the 1 st day until the 7th day of offspring rats. Meanwhile, sevoflurane reduced Bcl-2 and Hif-1αand increased Bax and cleaved-caspase 3 in the third day after birth. Hemin inhibits endogenous apoptosis by increasing Ngb and Hif-1α. And increased Ngb improved the damage of long-term learning and memory induced by sevoflurane and increased the number of neurons in the hippocampus. We concluded that Ngb can improve the neuronal injury induced by sevoflurane exposure by inhibiting apoptosis and increasing the number of neurons. And this protective effect of Ngb may be related to Hif-1α signaling pathway. This finding may provide a novel therapeutic approach for sevoflurane -induced nerve damage. [ABSTRACT FROM AUTHOR]