• Energy Research
• 3. Good health close
• FR close
• Energy Research close
• Neuroscience close

Prenatal restraint stress (PRS) in rats is associated with hippocampal dysfunctions and several behavioural and endocrine disorders related to this brain area. Recently, we have reported that the PRS modifies the hypothalamic-pituitary-adrenal (HPA) response to an ethanol challenge in adolescent animals. Since hippocampus is particularly sensitive to the deleterious effects of ethanol during adolescence, we investigated in this study the combined effects of PRS and ethanol administration on the oxidative status in the hippocampus of 28-day-old male rats. Thirty minutes after an intraperitoneal (i.p.) injection of ethanol (1.5 g/kg), the activities of several antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) but also non-enzymatic antioxidant (reduced glutathione) were assayed. Thiobarbituric acid reactive substances (TBARS) levels were also measured as a marker of lipid peroxidation. Ethanol enhanced superoxide dismutase activity in control rats but not in PRS rats. At basal level, catalase activity was lower in PRS rats than in control rats, indicating a potentially higher sensitivity to oxidative damages after this early stress. However, the hippocampal TBARS levels were not significantly affected by the ethanol administration, showing that an acute ethanol exposure does not induce oxidative damage in adolescent male rats. In conclusion, our data suggest that PRS affects both basal antioxidant status in the hippocampus and antioxidant response after an acute ethanol exposure. These findings extend previous works showing that PRS leads to hippocampal dysfunctions and raise the question of the potential increase of the hippocampal oxidative damage in PRS rats after repeated exposure to ethanol.

Our study aims at comparing in C57/Bl male mice, the impact of repeated injections of baclofen (an agonist of GABAB receptor) or diazepam (a benzodiazepine acting through a positive allosteric modulation of GABAA receptor) administered during the alcohol-withdrawal period on hippocampus-dependent memory impairments and brain regional glucocorticoid dysfunction after a short (1-week) or a long (4-week) abstinence. Hence, mice were submitted to a 6-month alcohol consumption (12%v/v) and were progressively withdrawn to water. Then, after a 1- or 4-weeks abstinence, they were submitted to a contextual memory task followed by measurements of corticosterone concentrations in the dorsal hippocampus (dHPC), the ventral hippocampus (vHPC) and the prefrontal cortex (PFC). Results showed that 1- and 4-week withdrawn mice exhibited a severe memory deficit and a significant abnormal rise of the test-induced increase of corticosterone (TICC) in the dHPC, as compared to water-controls or to mice still under alcohol consumption. Repeated daily systemic administrations of decreasing doses of diazepam (ranged from 0.5 to 0.12 mg/kg) or baclofen (ranged from 1.5 to 0.37 mg/kg) during the last 15 days of the withdrawal period, normalized both memory and TICC scores in the dHPC in 1-week withdrawn animals; in contrast, only baclofen-withdrawn mice showed both normal memory performance and TICC scores in the dHPC after a 4-week withdrawal period. In conclusion, the memory improvement observed in 4-week withdrawn mice administered with baclofen stem from the protracted normalization of glucocorticoid activity in the dHPC, a phenomenon encountered only transitorily in diazepam-treated withdrawn mice.

Uncontrolled consumption of alcohol is a hallmark of alcohol abuse disorders; however, the central molecular mechanisms underlying excessive alcohol consumption are still unclear. Here, we report that the GTP binding protein, H-Ras in the nucleus accumbens (NAc) plays a key role in neuroadaptations that underlie excessive alcohol-drinking behaviors. Specifically, acute (15 min) systemic administration of alcohol (2.5 g/kg) leads to the activation of H-Ras in the NAc of mice, which is observed even 24 h later. Similarly, rat operant self-administration of alcohol (20%) also results in the activation of H-Ras in the NAc. Using the same procedures, we provide evidence suggesting that the exchange factor GRF1 is upstream of H-Ras activation by alcohol. Importantly, we show that infection of mice NAc with lentivirus expressing a short hairpin RNA that targets the H-Ras gene produces a significant reduction of voluntary consumption of 20% alcohol. In contrast, knockdown of H-Ras in the NAc of mice did not alter water, quinine, and saccharin intake. Furthermore, using two-bottle choice and operant self-administration procedures, we show that inhibiting H-Ras activity by intra-NAc infusion of the farnesyltransferase inhibitor, FTI-276, produced a robust decrease of rats' alcohol drinking; however, sucrose consumption was unaltered. Finally, intra-NAc infusion of FTI-276 also resulted in an attenuation of seeking for alcohol. Together, these results position H-Ras as a central molecular mediator of alcohol's actions within the mesolimbic system and put forward the potential value of the enzyme as a novel target to treat alcohol use disorders.

To investigate the efficacy of percutaneous chemonucleolysis using ethanol gel (PCEG) in alleviating radicular pain due to disc herniation after failure of conservative treatment.After failure of conservative treatment, PCEG was performed under fluoroscopic guidance in 42 patients with sciatica >4/10 on a Visual Analog Scale (VAS) for at least 6 weeks and consistent disc herniation on MRI or CT <3 months. The VAS pain score was determined at baseline, then after 1 and 3 months. We assessed the influence of patient-related factors (age, gender, pain duration) and disc herniation-related factors (level, migration pattern, disc herniation-related spinal stenosis) on outcome of PCEG.Mean pain duration was 6.7 months. Pain intensity decreased by 44% and 62.6% after 1 and 3 months, respectively, versus baseline (P = 0.007). A mild improvement was noted by the rheumatologist in 30/42 (71.4%) and 36/42 (85.7%) patients after 1 and 3 months, respectively, and in 31/42 (73.8%) and 33/42 (78.6%) patients by self-evaluation. Patients who failed PCEG were significantly older (49.8 vs. 37.3 years, P = 0.03). None of the other variables studied were significantly associated with pain relief.PCEG may significantly improve disc-related radicular pain refractory to conservative treatment.• Percutaneous chemonucleolysis using ethanol gel (PCEG) is feasible on an outpatient basis. • PCEG improves disc-related radicular pain refractory to conservative treatment. • PCEG is feasible on an outpatient basis. • Failure of PCEG does not interfere with subsequent spinal surgery.

AbstractWith the current practice of therapeutic hypothermia for neonatal encephalopathy, disability rates and the severity spectrum of cerebral palsy are reduced. Nevertheless, safe and effective adjunct therapies are needed to optimize outcomes. This study’s objective was to assess if 18 mg/kg melatonin given rapidly over 2 h at 1 h after hypoxia-ischemia with cooling from 1–13 h was safe, achieved therapeutic levels within 3 h and augmented hypothermic neuroprotection. Following hypoxia-ischemia, 20 newborn piglets were randomized to: (i) Cooling 1–13 h (HT; n = 6); (ii) HT+ 2.5% ethanol vehicle (HT+V; n = 7); (iii) HT + Melatonin (HT+M; n = 7). Intensive care was maintained for 48 h; aEEG was acquired throughout, brain MRS acquired at 24 and 48 h and cell death (TUNEL) evaluated at 48 h. There were no differences for insult severity. Core temperature was higher in HT group for first hour after HI. Comparing HT+M to HT, aEEG scores recovered more quickly by 19 h (p < 0.05); comparing HT+V to HT, aEEG recovered from 31 h (p < 0.05). Brain phosphocreatine/inorganic phosphate and NTP/exchangeable phosphate were higher at 48 h in HT+M versus HT (p = 0.036, p = 0.049 respectively). Including both 24 h and 48 h measurements, the rise in Lactate/N-acetyl aspartate was reduced in white (p = 0.030) and grey matter (p = 0.038) after HI. Reduced overall TUNEL positive cells were observed in HT+M (47.1 cells/mm2) compared to HT (123.8 cells/mm2) (p = 0.0003) and HT+V (97.5 cells/mm2) compared to HT (p = 0.012). Localized protection was seen in white matter for HT+M versus HT (p = 0.036) and internal capsule for HT+M compared to HT (p = 0.001) and HT+V versus HT (p = 0.006). Therapeutic melatonin levels (15–30mg/l) were achieved at 2 h and were neuroprotective following HI, but ethanol vehicle was partially protective.

Several works have suggested a potential role for nitric oxide in alcohol-seeking behavior and we have recently shown that the specific blockade of the expression of the neuronal nitric oxide synthase (NOS1) decreases rat ethanol intake. Our previous results have also shown that chronic ethanol exposure has differential effect on the brain NOS activity depending on rat brain area. In the present study, we examine the effects of chronic administration of ethanol on the NOS1-mRNA levels measured with the competitive reverse transcriptase-polymerase chain reaction technique. Chronic administration of ethanol differentially regulated NOS1-mRNA levels depending on rat brain area. Chronic ethanol exposure had no effect on the NOS1-mRNA levels in frontal cortex, but decreased the NOS1-mRNA levels in hippocampus (P<0.01, 39% decrease) and induced a strong increase in striatum (P<0.01, 92% increase). These effects of ethanol were not affected by 7-nitro indazole (25 mg/kg, i.p. daily for 1 week) treatment. These data further support that NOS1 is regulated by chronic exposure to ethanol and that these effects are related to modifications of mRNA levels.

To describe the long-term clinical and morphological outcome of symptomatic hepatic cysts treated with percutaneous ethanol sclerotherapy (PES).From December 2003 to September 2011, all patients with hepatic cysts undergoing PES with a follow-up after 12 months were included. Evolution of the volume of the cysts and clinical and biological data were recorded. Features of the cyst were evaluated in each patient: simple, haemorrhagic or developed on underlying polycystic liver disease (PCLD).Fifty-eight cysts (median volume 666 mL) were treated in 57 patients (52 women, mean age 58 years (18-80)). Twenty-two patients (39 %) had simple hepatic cysts, 19 (33 %) had dominant cysts on PCLD and 20 had haemorrhagic cysts (34.5 %), including 4 with PCLD. After a mean 27.3 months of follow-up, the final median cystic volume was 13.5 mL (p < 0.0001), and the median reduction in cyst volume was 94 % (58-100 %). Treatment was satisfactory in 95 % of the patients (54/57) (symptoms disappeared in 45/57 (79 %), decreased in 9/57 (16 %)). There was no clinical or morphological difference between patients with PCLD, haemorrhagic cysts or simple cysts.The clinical and morphological efficacy of a single session of PES is very high, regardless of the presence of intracystic haemorrhage or underlying PCLD.• The clinical efficacy of percutaneous ethanol sclerotherapy is very high. • Haemorrhagic content should not be a contraindication for percutaneous sclerotherapy. • Dominant cysts on polycystic liver disease should be treated with PES. • Imaging follow-up should not be performed shortly after the procedure.