Mammalian target of rapamycin/p70 ribosomal S6 protein kinase signaling is altered by sevoflurane and/or surgery in aged rats.

The mammalian target of rapamycin (mTOR)/p70 ribosomal S6 protein kinase (p70S6k) pathway exerts anti­apoptotic effects that may contribute to disease pathogenesis. The memory impairment in patients with Alzheimer's disease (AD) has been suggested to be contributed to by abnormal mTOR signaling. The aim of the current study was to investigate the association between sevoflurane and/or surgery and AD through the mTOR/p70S6K signaling pathway. Sprague­Dawley rats were randomly assigned to the sevoflurane, surgery or control groups. The animals in the surgery group received a partial hepatectomy under sevoflurane anesthesia. The hippocampal levels of phosphorylated (p)­mTOR, p­p70S6K, caspase­3 and p­tau/total (t)­tau were analyzed. The Morris water maze (MWM) was used to evaluate cognitive function following treatment. The levels of p­mTOR and p­p70S6K were reduced, whereas caspase­3 levels were increased in the surgery group compared with the sevoflurane group. The p­tau/t­tau levels were increased, however, tau mRNA was unaffected by sevoflurane and/or surgery. The rats in the surgery group required a significantly longer time to locate the platform in the MWM test compared with the control and sevoflurane groups. Sevoflurane treatment and/or surgery reduced anti­apoptotic activity, and the postoperative cognitive dysfunction following surgery may be due to mTOR signaling pathway inhibition in aged rats. Increased neuronal apoptosis and tau phosphorylation are suggested to be involved in the association between anesthesia and AD occurrence.

Midazolam provides cytoprotective effect during corticosterone-induced damages in rat astrocytes by stimulating steroidogenesis.

Midazolam is a benzodiazepine derivative drug that has powerful anxiolytic, amnestic, hypnotic, and sedative properties. The cytoprotective effect of midazolam on brain astrocytes is poorly understood. This study aimed to investigate the cytoprotective effect of midazolam on astrocytes exposed to corticosterone, a stress-produced glucocorticoid. We found that midazolam stimulated pregnenolone and progesterone secretion in astrocytes in a dose-dependent manner. Midazolam protected astrocytes from corticosterone-induced damages in a dose-dependent manner. In addition, we demonstrated that progesterone reduced corticosterone-induced damages. Finally, we applied trilostane, an inhibitor of 3ß-hydroxysteroid dehydrogenase, to inhibit pregnenolone metabolism and found that pretreatment with trilostane significantly inhibited the cytoprotective effect of midazolam on corticosterone-induced cytotoxicity in rat astrocytes in a dose-dependent manner. Taken together, these results demonstrate that midazolam has cytoprotective effect on astrocytes. This is, at least partially, derived from midazolam-induced steroidogenesis including progesterone and downstream products in astrocytes. Our data provide new insights into the cytoprotective effect of midazolam.

Inhaled sevoflurane may promote progression of amnestic mild cognitive impairment: a prospective, randomized parallel-group study.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is thought to be a transitional stage between normal aging and the development of Alzheimer's disease (AD). Recent studies have suggested that the inhalational anesthetic isoflurane can induce caspase activation and apoptosis, increase aggregates of ß-amyloid (Aß) levels, and enhance Aß aggregation. The aim of this study was to investigate whether previous exposure to different anesthetics induced progression of aMCI. METHODS: A prospective, randomized parallel-group study was completed with 180 patients with aMCI who were randomly assigned to a sevoflurane, propofol or lidocaine epidural anesthesia group (n = 60 per group) during an L3 to L4 or an L4 to L5 spinal surgery. Sixty additional outpatients with aMCI served as a control group. Before surgery, all subjects underwent a neuropsychological assessment. Cerebrospinal fluid (CSF) was obtained by lumbar puncture, and neuropsychological assessments were completed in the clinic. CSF Aß42, total tau and phosphorylated tau181 were quantitatively assayed. The neuropsychological assessments were repeated after 2 years. RESULTS: Two years after anesthesia, the number of AD cases that emerged did not differ significantly between the groups. However, the number of cases of progressive MCI was greater in the sevoflurane group than in the control group. Age correlated linearly with aMCI progression, whereas sex did not. Both patients with AD and progressive MCI had decreased CSF Aß42, increased total tau and increased phosphorylated tau levels compared with those with stable MCI and the controls. CONCLUSIONS: Inhaled sevoflurane accelerated the progression of aMCI to progressive MCI in this selected Chinese population.

Comparison of neonatal tolerance to thoracoscopic and open repair of esophageal atresia with tracheoesophageal fistula.

BACKGROUND: Advances in minimally invasive surgical techniques and neonatal intensive care for neonates have allowed for repair of the neonatal esophageal atresia with tracheoesophageal fistula (EA/TEF) to be approached endoscopically. However, thoracoscopic surgery in children is still performed in only a few centers throughout the world. The aim of this study was to compare the neonatal tolerance to the thoracoscopic repair (TR) and the open repair (OR) and also to discuss anesthetic management in thoracoscopic procedure. METHODS: We performed a prospective study enrolling newborns diagnosed with EA with distal TEF (type C) receiving the repair surgery between June 2009 and January 2012 in our institution. Data collected included the newborns' gestational age and weight at the time of the operation, operative time, parameters of intraoperative mechanical ventilation, oxygenation, end-tidal carbon dioxide (ETCO2), and analysis of blood gases. Time to extubation and length of stay were also recorded. RESULTS: Intravenous induction with muscle paralysis followed by pressure-control ventilation and tracheal intubation regardless of the position of the fistula can be performed uneventfully in EA/TEF newborns with no additional airway anomalies and large, pericarinal fistulas in our experiences. The thoracoscopic approach appeared to take longer than the open approach. During the procedure of repair, hypercarbia and acidosis developed immediately 1 hour after pneumothorax in both groups. CO2 insufflation did have additional influence on the respiratory function of the newborns in the TR group; values of PaCO2 and ETCO2 were higher in the TR group but the difference did not reach statistical significance. By the end of the procedure, values of PaCO2 and ETCO2 returned to the baseline levels while pH did not, but all parameters made no difference in the two groups. Besides, time to extubation was shorter in the TR group. CONCLUSIONS: Thoracoscopic repair of EA/TEF is comparable to the open repair, and is believed to be safe and tolerable in selected patients. A wider range of neonates may be acceptable for thoracoscopic EA/TEF repair with increasing surgical experience.