α-lipoic acid attenuates spatial learning and memory impairment induced by hepatectomy.

The aim of the present study was to compare the effects of α-lipoic acid (ALA) on postoperative cognitive dysfunction (POCD) between wild type (WT) and leptin receptor-deficient (db/db) mice and to elucidate the underlying mechanism of treatment with ALA. The present study compared the effects of ALA on spatial learning and memory of WT and db/db mice using a Morris water maze following hepatectomy. The expression levels of proteins, including cyclin-dependent kinase 5 (Cdk5), tau, phosphorylated tau and amyloid ß (Aß) were measured in the hippocampus. Surgery impaired postoperative cognitive function in both WT and db/db mice. Furthermore, the expression levels of Cdk5 and Aß, and the phosphorylation of tau in the hippocampus increased after the surgery in both WT and db/db mice. The ultrastructure of hippocampal neurons and synapses was analyzed by transmission electron microscopy and the results revealed that surgery damaged the structure of neurons and synapses in both WT and db/db mice. Treatment with ALA protected the postoperative cognitive function and the structure of hippocampal neurons and synapses, and prevented the increase in protein expression levels of Cdk5 and Aß, and the phosphorylation of tau in the hippocampus of WT but not db/db mice. The results of the present study suggest that ALA may be used for the treatment of POCD. The molecular mechanisms underlying the activity of ALA require further investigation.

Risk factors for early postoperative cognitive dysfunction after colorectal surgery.

BACKGROUND: It has been reported that postoperative cognitive dysfunction (POCD) is correlated with the degeneration of the central nervous system, oxidative stress, inflammation, and endocrine and immune dysfunction. Increased age, predisposed comorbidity, long surgery time, and prolonged stay in the intensive care unit have been reported to be risk factors for developing POCD for cardiac surgery. In the present study, the risk factors of early POCD after colorectal surgery were investigated. METHODS: Eighty patients, who provided informed consents for their participation in this study, were enrolled and received colorectal surgery under general anesthesia. Neuropsychological tests were performed preoperatively and on postoperative day seven. The risk factors for POCD were analyzed using a multivariate logistic regression model. RESULTS: Nineteen patients were diagnosed with POCD (24.7%). Diabetes history (OR = 8.391 [2.208-31.882], P = 0.012), fasting over 3 days after surgery (OR = 5.236 [1.998-13.721], P = 0.001) and an SIRS score of > 3 on the second day after surgery (OR = 6.995 [1.948-25.111], P = 0.003) were risk factors for early POCD in colorectal cancer patients. CONCLUSION: The risk factors for early POCD after colorectal surgery included diabetes history, fasting over 3 days, and an SIRS score of > 3 on the second day.

Aquaporin-4 knockout mice exhibit increased hypnotic susceptibility to ketamine.

PURPOSE: This study examines anesthetic/hypnotic effects of ketamine in AQP4 knockout (KO) and wild-type (WT) mice with the particular focus on neurotransmission. MATERIALS AND METHODS: Ketamine (100 mg/kg) was intraperitoneally injected in 16 WT and 16 KO mice. The hypnotic potencies were evaluated by the loss of the righting reflex (LORR). The amino acids neurotransmitter levels in prefrontal cortex were measured by microdialysis. RESULTS: This study demonstrated that AQP4 knockout significantly shortened the latency compared with WT mice (98.0 ± 4.2 vs. 138.1 ± 15.0 s, p < .05) and prolonged duration of LORR (884.7 ± 58.6 vs. 562.0 ± 51.7 s, p < .05) compared with WT mice in LORR induced by ketamine. Microdialysis showed that lack of AQP4 markedly decreased glutamate level within 20 min (p < .05) and increased γ-aminobutyric acid (GABA) level within 30-40 min (p < .05) after use of ketamine. Moreover, the levels of taurine were remarkably higher in KO mice than in WT mice, but no obvious differences in aspartate were observed between two genotypes. CONCLUSION: AQP4 deficiency led to more susceptibility of mice to ketamine, which is probably due to the modulation of specific neurotransmitters, hinting an essential maintenance of synaptic activity mediated by AQP4 in the action of ketamine.