Curcumin promotes the survival of ischemic random skin flaps via autophagy.

Random skin flaps have been widely applied in reconstructive and plastic surgery; however, necrosis usually happens due to insufficient blood supply in the ischemic area of flaps. Curcumin (CUR) is a primary bioactive compound of turmeric (Curcuma longa, L.), which has been proven to be effective on anticancer, decreasing oxidative stress and apoptosis through activating autophagy, and promoting angiogenesis in ischemic tissue. Therefore, the potential therapeutic effect of CUR on promoting survival of ischemic random skin flaps and its underlying mechanism associated with autophagy were investigated. After establishment of dorsal random skin flaps, sixty mice were randomly divided into three groups: Control, CUR or CUR+3-methyladenine (3-MA, an autophagy inhibitor). The results showed that CUR increased the viability area and blood flow as well as relieved the edema of skin flaps through promoting angiogenesis, decreasing oxidative stress, and inhibiting apoptosis of the ischemic area. Further study confirmed that CUR activated autophagy in the random skin flaps, and 3-MA effectively reversed the effect on viability, neovascularization, oxidative stress and apoptosis, suggesting autophagy played a vital role in these CUR's protective effect on random skin flaps. Moreover, this CUR-induced autophagy should be mediated through downregulating the PI3K/AKT/mTOR signaling pathway. Together with secondary response of increased angiogenesis, reduced oxidative stress and apoptosis, CUR effectively improved survival of random skin flaps in vivo. To sum up, our research showed the great potential of CUR using as a promising flap protective therapy for random skin flap survival and regeneration.

The effects of early exposure to MK-801 during environmental enrichment on spatial memory, methamphetamine self-administration and cue-induced renewal in rats.

OBJECTIVE: Accumulating evidence indicates an association between improved cognition and the early introduction of environmental enrichment (EE). The beneficial effect of EE has also been examined in the field of methamphetamine (METH) dependence. The present study was designed to examine whether early cognitive alterations by dizocilpine (MK-801) in adolescence can impact the effect of EE on spatial memory, METH self-administration (SA), and cue-induced renewal in adulthood. METHODS: In Experiments 1 and 2, Morris Water Maze (MWM) performance, c-Fos expression and N-methyl d-aspartate receptor subtype 2B (NMDAR2B) levels were determined in various brain regions following a change in rearing condition from EE to an isolation environment (IE) at different points (PD 41-60 or PD 51-70). In Experiments 3 and 4, MWM performance and METH SA behaviors in adulthood were tested following adolescent administration of MK-801 during different periods of adolescence (PD 41-60 or PD 51-70) under EE rearing conditions. RESULTS: The early introduction of the IE at PD 41-60 significantly decreased the beneficial effect of EE on MWM performance in adulthood as compared to IE exposure at PD 51-70. Different rearing conditions also altered c-Fos expression and NMDA2B receptor activity in a regionally specific pattern. EE induced structural and systemic changes in the hippocampus that were associated with improvements in spatial memory. Early administration of MK-801 at PD 41-60 and PD 51-70 produced distinctive effects on the behavioral outcomes of METH SA and cue-induced renewal. CONCLUSION: Early cognitive alterations have a profound impact on spatial memory and METH dependence.

Ketamine abuse potential and use disorder.

Ketamine is a noncompetitive antagonist of N-methyl-d-asparate (NMDA) receptor and has been long used as an anesthetic agent in humans and veterinary medicine. The present article reviews the epidemiology, pharmacology, neurochemistry, and treatment of ketamine abuse. Ketamine has a unique mood controlling property and a number of studies have demonstrated a significant and rapid antidepressant effect of ketamine. However, the therapeutic value of ketamine to treat psychiatric disorders faces a major challenge that ketamine also owns significant reinforcing and toxic effects. Its abuse has posted severe harms on individuals and society. Disrupted learning and memory processing has long been related with ketamine use. It is hypothesized that ketamine blocks NMDA receptors on gamma-aminobutyric acid (GABA) neurons inside the thalamic reticular nucleus, which leads to disinhibition of dopaminergic neurons and increased release of dopamine. Currently, there is no specific treatment for treating every ketamine patient presenting peripheral toxicity. Interestingly, ketamine psychotherapy has been suggested to be a promising approach to treat addiction of other drugs. Future research can continue to develop creative ways to investigate potential mechanism and treatments related to ketamine abuse that have posted severe individual and social harms.