Effect of lacosamide on ethanol induced conditioned place preference and withdrawal associated behavior in mice: Possible contribution of hippocampal CRMP-2

BackgroundExcessive consumption of ethanol is known to activate the mTORC1 pathway and to enhance the Collapsin Response Mediator Protein-2 (CRMP-2) levels in the limbic region of brain. The latter helps in forming microtubule assembly that is linked to drug taking or addiction-like behavior in rodents. Therefore, in this study, we investigated the effect of lacosamide, an antiepileptic drug and a known CRMP-2 inhibitor, which binds to CRMP-2 and inhibits the formation of microtubule assembly, on ethanol-induced conditioned place preference (CPP) in mice.MethodsThe behavior of mice following ethanol addiction and withdrawal was assessed by performing different behavioral paradigms. Mice underwent ethanol-induced CPP training with alternate dose of ethanol (2 g/kg, po) and saline (10 ml/kg, po). The effect of lacosamide on the expression of ethanol-induced CPP and on ethanol withdrawal associated anxiety and depression-like behavior was evaluated. The effect of drug on locomotor activity was also assessed and hippocampal CRMP-2 levels were measured.ResultsEthanol-induced CPP was associated with enhanced CRMP-2 levels in the hippocampus. Lacosamide significantly reduced the expression of ethanol-induced CPP and alleviated the levels of hippocampal CRMP-2 but aggravated withdrawal-associated anxiety and depression in mice.ConclusionThe present study demonstrated the beneficial effect of lacosamide in attenuation of expression of ethanol induced conditioned place preference via reduction of hippocampal CRMP-2 level. These findings suggest that lacosamide may be investigated further for ethanol addiction but not for managing withdrawal.     

温针灸对功能性便秘患者临床症状及焦虑抑郁的改善作用

目的:探讨温针灸对功能性便秘(FC)患者临床症状及焦虑抑郁的改善作用。方法:选取2017年1月至2017年12月中国中医科学院广安门医院南区收治的FC患者70例作为研究对象,随机分为观察组和对照组,每组35例。对照组采用常规针刺治疗,观察组采用温针灸治疗,比较治疗前后2组患者便秘临床症状积分、首次排便时间、中医证候评分、焦虑自评量表(SAS)、抑郁自评量表(SDS)评分。结果:观察组有效率96. 00%,对照组有效率68. 00%,差异有统计学意义(P0. 05)。治疗后2组患者的周排便次数、粪便性状积分和排便困难程度均改善,中医证候评分、SAS和SDS评分下降,较治疗前差异有统计学意义(P 0. 05)。治疗后,观察组患者的周排便次数、粪便性状积分高于对照组,中医证候评分、SDS和SAS评分、首次排便时间以及排便困难程度积分小于对照组,差异有统计学意义(P 0. 05)。结论:温针灸治疗能调节胃肠道运动、润湿肠道、显著改善便秘等临床症状,对FC患者有显著临床效果。     

Acute and subsequent continuation electroconvulsive therapy elevates serum BDNF levels in patients with major depression

IntroductionThe induction of brain-derived neurotrophic factor (BDNF) release and subsequent restoration of neuroplastic homeostasis may underlie the effects of electroconvulsive therapy (ECT).ObjectivesWe aimed to assess serum and plasma BDNF levels during the course of acute ECT, as well as before and after subsequent continuation ECT, in patients with depression.MethodsWe included 24 patients with major depressive disorder (mean age ± SD: 54.5 ± 13.7; f/m: 17/7; baseline 17-item Hamilton Depression Rating Scale score of 26.79 ± 4.01). Serum and plasma BDNF (sBDNF, pBDNF) levels were assessed at nine time-points before, during, and after acute ECT series. Data were analysed using linear regression and linear mixed models, which were adjusted for multiple comparisons via Bonferroni correction. Five patients received continuation ECT subsequent to the acute ECT series. In these patients, BDNF levels were assessed before and after each two continuation ECT sessions using Wilcoxon signed-rank tests.ResultsRelative to baseline (mean ng/ml ±SD: 24.68 ± 14.40), sBDNF levels were significantly higher 1 day (33.04 ± 14.11, p = 0.013, corrected), 1 week (37.03 ± 10.29, p < 0.001, corrected), and 1 month (41.05 ± 10.67, p = 0.008, corrected) after the final ECT session, while pBDNF levels did not significantly differ (p > 0.1). Furthermore, our results indicated that sBDNF levels increased after each continuation ECT session. There was no significant association between sBDNF levels and clinical parameters or treatment response.ConclusionThe absence of an association between changes in sBDNF levels and depressive symptoms challenges the proposed concept of sBDNF/pBDNF as key markers of the effects of ECT.     

Chemogenetic Silencing of the Locus Coeruleus–Basolateral Amygdala Pathway Abolishes Pain-Induced Anxiety and Enhanced Aversive Learning in Rats

BackgroundPain affects both sensory and emotional aversive responses, often provoking anxiety-related diseases when chronic. However, the neural mechanisms underlying the interactions between anxiety and chronic pain remain unclear.MethodsWe characterized the sensory, emotional, and cognitive consequences of neuropathic pain (chronic constriction injury) in a rat model. Moreover, we determined the role of the locus coeruleus (LC) neurons that project to the basolateral amygdala (BLA) using a DREADD (designer receptor exclusively activated by designer drugs).ResultsChronic constriction injury led to sensorial hypersensitivity in both the short term and long term. Otherwise, long-term pain led to an anxiety-like profile (in the elevated zero maze and open field tests), as well as increased responses to learn aversive situations (in the passive avoidance and fear conditioning tests) and an impairment of nonemotional cognitive tasks (in the novel object recognition and object pattern of separation tests). Chemogenetic blockade of the LC-BLA pathway and intra-BLA or systemic antagonism of beta-adrenergic receptors abolished both long-term pain-induced anxiety and enhanced fear learning. By contrast, chemogenetic activation of this pathway induced anxiety-like behaviors and enhanced the aversive learning and memory index in sham animals, although it had little effect on short- and long-term chronic constriction injury animals. Interestingly, modulation of LC-BLA activity did not modify sensorial perception or episodic memory.ConclusionsOur results indicate that dimensions associated with pain are processed by independent pathways and that there is an overactivation of the LC-BLA pathway when anxiety and chronic pain are comorbid, which involves the activity of beta-adrenergic receptors.     

Mechanical Thrombectomy in Acute Ischemic Stroke—The Role of Interventional Cardiologists: A Prospective Single-Center Study

ObjectivesThe aim of this study was to assess the safety and outcomes of mechanical thrombectomy (MT) performed at a stroke center by interventional cardiologists (ICs) compared with other interventionists. The primary endpoint was functional independence of stroke survivors (modified Rankin scale score 0-2) at 3 months. The secondary endpoints included recanalization rate, reduction in stroke severity, and 3-month mortality.BackgroundMT is a validated treatment for large vessel occlusion acute ischemic stroke. Incorporating ICs with their infrastructure into a comprehensive stroke team may increase the accessibility of this therapy.MethodsIn this single-center, prospective study, we included 248 ischemic stroke patients (mean age 68 ± 13 years, 48% women) with confirmed large vessel occlusion. The procedures were performed by ICs (n = 80), vascular surgeons (n = 116), and neuroradiologists (n = 52).ResultsFunctional independence after 3 months was similar between patients operated by cardiologists and other specialists (modified Rankin scale score 0-2 in 44% vs 55%; P = 0.275). Similarly, the mortality rate at 3 months did not differ (28% vs 31%; P = 0.585). Procedures performed by cardiologists took longer than those performed by other specialists (120 minutes vs 105 minutes; P = 0.020). A percentage of procedures with angiographic success (TICI [Thrombolysis In Cerebral Infarction] grade 2b or 3) was lower when performed by cardiologists (55.7% vs 71.7%; P = 0.013), but the change in stroke severity (National Institutes of Health Stroke Scale score after 24 hours) was similar.ConclusionsEndovascular treatment in stroke provided by interventional cardiologists in cooperation with noninvasive stroke specialists is noninferior to procedures performed by the other endovascular specialists. Mortality and functional independence after 3 months are similar regardless of an interventionist performing the procedure.     

Restoration of functional network state towards more physiological condition as the correlate of clinical effects of pallidal deep brain stimulation in dystonia

BackgroundDeep brain stimulation of the internal globus pallidus (GPi DBS) is an invasive therapeutic modality intended to retune abnormal central nervous system patterns and relieve the patient of dystonic or other motor symptoms.ObjectivesThe aim of the presented research was to determine the neuroanatomical signature of GPi DBS modulation and its association with the clinical outcome.MethodsThis open-label fixed-order study with cross-sectional validation against healthy controls analysed the resting-state functional MRI activity changes induced by GPi DBS in 18 dystonia patients of heterogeneous aetiology, focusing on both global (full brain) and local connectivity (local signal homogeneity).ResultsCompared to the switched-off state, the activation of GPi DBS led to the restoration of global subcortical connectivity patterns (in both putamina, diencephalon and brainstem) towards those of healthy controls, with positive direct correlation over large-scale cortico-basal ganglia-thalamo-cortical and cerebellar networks with the clinical improvement. Nonetheless, on average, GPi DBS also seemed to bring local connectivity both in the cortical and subcortical regions farther away from the state detected in healthy controls. Interestingly, its correlation with clinical outcome showed that in better DBS responders, local connectivity defied this effect and approached healthy controls.ConclusionsAll in all, the extent of restoration of both these main metrics of interest towards the levels found in healthy controls clearly correlated with the clinical improvement, indicating that the restoration of network state towards more physiological condition may be a precondition for successful GPi DBS outcome in dystonia.     

Transjugular Renal Biopsy Bleeding Risk and Diagnostic Yield: A Systematic Review

This study aimed to better define the safety and efficacy of transjugular renal biopsy (TJRB) based on published studies. Seventeen published articles were included (1,321 biopsies). Complications were classified as major if they resulted in blood transfusion or additional invasive procedures. All other bleeding complications were considered minor. Diagnostic tissue was obtained in 1,193 procedures (90.3%). The total incidence of bleeding complications among 15 articles with complete data was 202 of 892 procedures (22.6%): 162 (18.2%) minor and 40 (4.5 %) major. These results show that TJRB is a feasible procedure for obtaining renal tissue for diagnosis and that most complications are self-limiting.     

Five‐year efficacy of finasteride in 801 Japanese men with androgenetic alopecia

Finasteride is standard medical treatment for androgenetic alopecia; however, no large studies with 5 years or more of follow up have been performed in Japan. The authors followed Japanese men with androgenetic alopecia treated with finasteride for 5 years to evaluate long‐term treatment efficacy. Of 903 men treated with finasteride (1 mg/day), 801 patients were evaluated over 5 years by modified global photographic assessment. Although the proportion of improvement was high (99.4%), modified global photographic assessment scores after 5 years of treatment were lower in patients with more advanced disease as measured by the modified Norwood–Hamilton scale. After separating patients into “sufficient” and “insufficient” efficacy groups according to the modified global photographic assessment score after 5 years (scores ≥6 and <6, respectively), multivariate analysis showed that independent risk factors of insufficient efficacy were age at start of treatment of 40 years or more (P = 0.021) and classification on the modified Norwood–Hamilton scale (P < 0.001), whereas presence of stress at start of treatment was a negative predictor (P = 0.025). In conclusion, continuous finasteride treatment for 5 years improved androgenetic alopecia with sustained effect among Japanese. Younger age and less advanced disease at start of treatment were the key predictors of higher finasteride efficacy.