Protocol on transcranial alternating current stimulation for the treatment of major depressive disorder: a randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD). The study is to evaluate the efficacy and safety of tACS treating MDD.@*METHODS@#This is an 8-week, double-blind, randomized, placebo-controlled study. Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), following a 4-week observation period (week 8). The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8. Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17, the proportion of participants having improvement in the clinical global impression-improvement, the change in HDRS-17 score (range, 0-52, with higher scores indicating more depression) over the study, and variations of brain imaging and neurocognition from baseline to week 4. Safety will be assessed by vital signs at weeks 4 and 8, and adverse events will be collected during the entire study.@*DISCUSSION@#The tACS applied in this trial may have treatment effects on MDD with minimal side effects.@*TRIAL REGISTRATION@#Chinese Clinical Trial Registry, ChiCTR1800016479; http://www.chictr.org.cn/showproj.aspx?proj=22048.

Correlation between RoPE score and right-to-left shunt severity in patients with cryptogenic stroke / 西安交通大学学报(医学版)

Objective To compare the clinical features between cryptogenic stoke(CS)with and without right-to-left shunt(RLS)so as to determine whether shunt severity determined by control-enhanced transcranial Doppler(c-TCD)is correlated with the risk of paradoxical embolism(RoPE)score.Methods We made a retrospective analysis of clinical characteristics of 138 CS patients with and without RLS admitted to our department between January 2014 and November 2016.For patients documented by c-TCD,we evaluated whether there was a correlation between RLS severity and RoPE score. RLS was diagnosed by c-TCD and contrast-enhanced transthoracic echocardiography(c-TTE).We compared every modality for detecting RLS with and without Valsalva maneuver.For patients found with RLS in c-TCD and c-TTE,we judged whether there was an agreement in grading RLS between two modalities.Results For patients with CS,shunt severity by c-TCD was positively correlated with RoPE score(r= 0.26,P= 0.05).The clinical features were different between CS patients with RLS and without RLS.Compared with the positive results of c-TCD and c-TTE at rest,the positive rate was higher in Valsalva maneuver,respectively(P＜0.01).There was a moderate agreement between shunt grades identified by the two techniques(Kappa=0.428).Conclusion There is a positive correlation between RoPE score and RLS severity determined by c-TCD in CS patients.Valsalva maneuver can significantly increase the positive rate of RLS detected by c-TCD and c-TTE.

Relationships between Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases: Clinical Assessments, Biomarkers, and Treatment / 中华医学杂志(英文版)

<p><b>Objective</b>Rapid eye movement sleep behavior disorder (RBD) is characterized by dream enactment and loss of muscle atonia during rapid eye movement sleep. RBD is closely related to α-synucleinopathies including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Many studies have investigated the markers of imaging and neurophysiological, genetic, cognitive, autonomic function of RBD and their predictive value for neurodegenerative diseases. This report reviewed the progress of these studies and discussed their limitations and future research directions.</p><p><b>Data Sources</b>Using the combined keywords: "RBD", "neurodegenerative disease", "Parkinson disease", and "magnetic resonance imaging", the PubMed/MEDLINE literature search was conducted up to January 1, 2018.</p><p><b>Study Selection</b>A total of 150 published articles were initially identified citations. Of the 150 articles, 92 articles were selected after further detailed review. This study referred to all the important English literature in full.</p><p><b>Results</b>Single-nucleotide polymorphisms in SCARB2 (rs6812193) and MAPT (rs12185268) were significantly associated with RBD. The olfactory loss, autonomic dysfunction, marked electroencephalogram slowing during both wakefulness and rapid eye movement sleep, and cognitive impairments were potential predictive markers for RBD conversion to neurodegenerative diseases. Traditional structural imaging studies reported relatively inconsistent results, whereas reduced functional connectivity between the left putamen and substantia nigra and dopamine transporter uptake demonstrated by functional imaging techniques were relatively consistent findings.</p><p><b>Conclusions</b>More longitudinal studies should be conducted to evaluate the predictive value of biomarkers of RBD. Moreover, because the glucose and dopamine metabolisms are not specific for assessing cognitive cognition, the molecular metabolism directly related to cognition should be investigated. There is a need for more treatment trials to determine the effectiveness of interventions of RBD on preventing the conversion to neurodegenerative diseases.</p>

Effects of recombinant human erythropoietin on brain-derived neurotrophic factor expression in different brain regions of aging rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the effect of recombinant human erythropoietin (rhEPO) on expression of brain-derived neurotrophic factor (BDNF) in different brain regions of aging rats.</p><p><b>METHODS</b>Forty male SD rats were randomized equally into negative control group, D-galactose group, EPO treatment group, and positive control group. Rat models of subacute aging were established by continuous subcutaneous injection of 5% D-galactose. Immunohistochemical staining was used to analyze the variation of BDNF expressions in different brain regions of the aging rats with different treatments.</p><p><b>RESULTS</b>Significant brain region-specific differences in BDNF expression were found among the rats in different groups. Compared with those in the negative control group, the numbers of BDNF-positive cells in the hippocampal CA1 region, CA3 region, dentate gyrus (DG) and frontal cortex were all decreased obviously in D-galactose group (P<0.05) but increased in both EPO group and the positive control group (P<0.05) without significant differences between the latter two groups. In the rats in the same group, the number of BDNF-positive cells varied markedly in different brain regions (P<0.05), and the expression level of BDNF was the highest in the frontal cortex followed by the hippocampal CA3 region and the dentate gyrus, and was the lowest in the hippocampal CA1 region.</p><p><b>CONCLUSION</b>Treatment with rhEPO enhances the expression of BDNF in rat neural cells, suggesting that rhEPO may protect the nervous system from aging by regulating the BDNF pathway.</p>

Comparison Study of Polysomnographic Features in Multiple System Atrophy-cerebellar Types Combined with and without Rapid Eye Movement Sleep Behavior Disorder / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The brain stem is found to be impaired in multiple system atrophy-cerebellar types (MSA-C). Rapid eye movement (REM) sleep behavior disorder (RBD) is reported as a marker of progressive brain stem dysfunction. Few systematic studies about the sleep disturbances in MSA-C patients combined with or without RBD were reported. This study aimed to explore the polysomnographic (PSG) features of sleep disturbances between MSA-C patients with and without RBD.</p><p><b>METHODS</b>Totally, 46 MSA-C patients (23 with RBD, and 23 without RBD) were enrolled in this study. All patients underwent a structured interview for their demographic data, history of sleep pattern, and movement disorders; and then, overnight video-PSG was performed in each patient. All the records were evaluated by specialists at the Sleep Medicine Clinic for RBD and the Movement Disorder Clinic for MSA-C. The Student's t-test, Mann-Whitney U-test for continuous variables, and the Chi-square test for categorical variables were used in this study.</p><p><b>RESULTS</b>MSA-C patients with RBD had younger visiting age (52.6 ± 7.4 vs. 56.7 ± 6.0 years, P = 0.046) and shorter duration of the disease (12.0 [12.0, 24.0] vs. 24.0 [14.0, 36.0] months, P = 0.009) than MSA-C patients without RBD. MSA-C with RBD had shorter REM sleep latency (111.7 ± 48.2 vs. 157.0 ± 68.8 min, P = 0.042), higher percentage of REM sleep (14.9% ±4.0% vs. 10.0% ± 3.2%, P = 0.019), and lower Stage I (9.5% ±7.2% vs. 15.9% ±8.0%, P = 0.027) than MSA-C without RBD. Moreover, MSA-C patients with RBD had more decreased sleep efficiency (52.4% ±12.6% vs. 65.8% ±15.9%, P = 0.029) than that without RBD.</p><p><b>CONCLUSIONS</b>In addition to the RBD, MSA-C patients with RBD had other more severe sleep disturbances than those without RBD. The sleep disorders of MSA patients might be associated with the progress of the disease.</p>

Repetitive Transcranial Magnetic Stimulation for the Treatment of Restless Legs Syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique used to alter cortex excitability that has been proposed as an efficient method for treating brain hyperexcitability or hypoexcitability disorders. The aim of this study was to investigate whether high-frequency rTMS could have any beneficial effects in restless legs syndrome (RLS).</p><p><b>METHODS</b>Fourteen patients with RLS were given high-frequency rTMS (15 Hz, 100% motor threshold) to the leg representation motor cortex area of the frontal lobe for 14 sessions over 18 days. Patients were diagnosed according to the international criteria proposed by the International Restless Legs Syndrome Study Group in 2003. The International RLS Rating Scale (IRLS-RS), Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale were used to evaluate the severity of RLS, sleep quality, anxiety and depression, respectively. The scale scores were evaluated at four-time points (baseline, end of the 14 th session, and at 1- and 2-month posttreatment). One-way analysis of variance was used to compare scale scores at different time points.</p><p><b>RESULTS</b>There was significant improvement in the IRLS-RS (from 23.86 ± 5.88 to 11.21 ± 7.23, P < 0.05), PSQI (from 15.00 ± 4.88 to 9.29 ± 3.91, P < 0.05), and HAMA (from 17.93 ± 7.11 to 10.36 ± 7.13, P < 0.05) scale scores at the end of 14 th session, with ongoing effects lasting for at least 2 months.</p><p><b>CONCLUSIONS</b>High-frequency rTMS can markedly alleviate the motor system symptoms, sleep disturbances, and anxiety in RLS patients. These results suggest that rTMS might be an option for treating RLS.</p>

Characteristic of microglial activation of hippocampus in experimental epileptic rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the characteristics of microglial activation of hippocampus in experimental epileptic rats.</p><p><b>METHODS</b>Morphological changes and proliferation of OX-42 positive cells were compared at different time points after status of epilepticus (SE) in lithium-pilocarpine induced epileptic rats.</p><p><b>RESULTS</b>OX-42 positive cells were activated after SE, which increased to a peak at 3-7 d and in a relatively stable state at 7-14 d; then gradually decreased after 14d and returned to slightly higher level than previously at 21 d.</p><p><b>CONCLUSION</b>Inflammatory injury, microglial activation and cell proliferation are closely related after seizures, microglial activation may be an important mechanism in the inflammatory injury of epilepsy.</p>

Expression of hypoxia inducible factor-1alpha in different brain regions in aged rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the distribution of hypoxia inducible factor-1alpha (HIF-1alpha) in different brain regions in aged rats and investigate the role of HIF-1alpha in the aging process of the nervous system.</p><p><b>METHODS</b>The Nissl bodies and HIF-1alpha expression in different brain regions were observed in rats aged 3 and 30 months using Nissl staining and immunohistochemical method, respectively.</p><p><b>RESULTS</b>In the 30-month-old rats, the neural cells in 4 different brain regions presented with large cell body and loose alignment, containing reduced Nissl bodies in the cytoplasm. Compared with the 3-month-old rats, the aged rats showed greater number of HIF-1alpha-positive cells in the brain (P < 0.01), and the number varied significantly between the different brain regions (P < 0.01). The CA3 region contained the greatest number of positive cells, which were fewer in the motor cortex and cerebellum.</p><p><b>CONCLUSION</b>The capacity for protein synthesis in the neural cells is weakened but the expression of HIF-1alpha increased in aged rats, suggesting the important role that HIF-1alpha may play in the aging process of the nervous system, especially in hypomnesis.</p>