Brain-derived neurotrophic factor and post-stroke depression

Brain-derived neurotrophic factor (BDNF) is well known to play a critical role in cognition. Its role in mood disorders, including post stroke depression (PSD), is also recognized with more evidence surfacing. In patients with PSD, their serum BNDF level is lower than in those without depression. Furthermore, antidepressants could enhance BDNF expression in the brain, resulting in an alleviation of depression symptoms. Such therapeutic effect can be abolished in animals with the BDNF gene deleted. In PSD patients, the presence of stroke may contribute to the development of depression, including affecting the expression of BDNF. However, the mechanisms of BDNF in the development of PSD remain largely unknown. Lower BDNF levels may have existed in some patients before stroke onset, making them vulnerable to develop depressive symptoms. Meanwhile, the hypoxic environment induced by stroke could possibly downregulate BDNF expression in the brain. Current antidepressant treatments are not specific for PSD and there is a lack of treatments to address the linkage between stroke and PSD. This review summarizes the current knowledge of BDNF in PSD. By regulating BDNF expression, a synergistic effect may be achieved when such treatments are applied together with existing antidepressants.     

Tract-based analysis of target engagement by subcallosal cingulate deep brain stimulation for treatment resistant depression

BackgroundDeep brain stimulation (DBS) of subcallosal cingulate cortex (SCC) is a promising investigational therapy for treatment-resistant depression (TRD). However, outcomes vary, likely due to suboptimal DBS placement. Ideal placement is proposed to stimulate 4 SCC white matter bundles; however, no quantitative data have linked activation of these target tracts to response.ObjectiveHere we used the volume of tissue activated (VTA) and probabilistic diffusion tensor imaging (DTI) to quantify tract activation relating to response.MethodsDTI was performed in 19 TRD patients who received SCC-DBS. We defined clinical response as >48% reduction from baseline in the Hamilton Depression Rating Scale. Bilateral VTAs were generated based on subject-specific stimulation parameters. Patient-specific tract maps emanating from the VTAs were calculated using whole-brain probabilistic DTI. The four target tracts were isolated using tract-specific quantification and examined for overlap with DBS activated tissue.ResultsMedial frontal and temporal projections were stimulated in all responders at 6 and 12 months. Individual tract-based generalized linear mixed model analysis revealed a significant tract-by-response interaction at both 6 (F(1,135) = 3.828, p = 0.001) and 12 (F(1,135) = 5.688, p < 0.001) months, with post hoc tests revealing a response-related increase in cingulum activation at 6 months (t(135) = 2.418, p = 0.017) and decrease in forceps minor activation at 12 months (t(135) = -2.802, p = 0.006).ConclusionsA wider profile of white matter tracts, particularly to the medial frontal, was associated with DBS response. Cingulum bundle stimulation may promote early response and excess stimulation of the forceps minor might be detrimental. Our work supports prospective patient-specific targeting to inform personalized DBS.     

难治性颞叶癫痫患者脑组织脑源性神经营养因子表达明显高于正常对照者

脑源性神经营养因子在癫痫中的作用一直备受争议,现有的研究多为动物实验研究结果,本文采用光镜及电镜技术,观察24例难治性颞叶癫痫患者致痫灶组织病理及超微结构变化,结果显示颞叶癫痫患者致痫灶神经元变性,胶质细胞增生,细胞核空泡化,可见嗜神经细胞现象,免疫电镜及免疫组化显示难治性颞叶癫痫患者脑组织脑源性神经营养因子表达明显多于正常对照者,证实难治性癫痫患者致痫灶病理改变明显,且与脑源性神经营养因子表达变化有关。     

Deep brain stimulation in the treatment of depression

Blomstedt P, Sjöberg RL, Hansson M, Bodlund O, Hariz MI. Deep brain stimulation in the treatment of depression. Objective: To present the technique of deep brain stimulation (DBS) and to evaluate the studies conducted on DBS in the treatment of therapy‐refractory major depressive disorder (MDD). Method: A review of the literature on DBS in the treatment of MDD was conducted. Results: The results of DBS in MDD have been presented in 2 case reports and 3 studies of 47 patients operated upon in 5 different target areas. Positive effects have been presented in all studies and side effects have been minor. DBS in the nucleus accumbens resulted in a mean reduction of Hamilton depression rating scale (HDRS) of 36% after 1 year and 30% of the 10 patients achieved remission. DBS in the internal capsule/ventral striatum resulted in a reduction of 44% after 1 year, and at the last evaluation after in mean 2 years, 40% of the 15 patients were in remission. The 20 patients with subcallosal cingulated gyrus DBS had a reduction of HDRS of 52% after 1 year, and 35% were within 1 point from remission or in remission. Conclusion: DBS is a promising treatment for therapy‐refractory MDD. The published experience is, however, limited, and the method is at present an experimental therapy.     

丘脑底核脑深部电刺激对帕金森病抑郁障碍的影响

目的探讨丘脑底核脑深部电刺激对帕金森病病人抑郁障碍的疗效及其机制。方法回顾性分析21例帕金森病合并抑郁障碍病人的临床资料,均行丘脑底核脑深部电刺激术,术前及术后3、6个月分别应用汉密尔顿抑郁量表(HAMD)评分和统一帕金森病评定量表(UPDRS)运动评分对抑郁障碍和运动功能进行临床评价并分析其相关性。结果术后UPDRS运动评分和HAMD评分均显著下降(均P0.05),但是抑郁症状的改善与运动功能的改善并没有明显的相关性(P0.05)。结论丘脑底核脑深部电刺激能够明显改善帕金森病病人的抑郁症状,其机制可能与丘脑底核受到刺激影响脑内神经递质的变化有关,术后运动功能的改善不是抑郁症状改善的主要原因。     

难治性抑郁症患者血清脑源性神经营养因子动态分析

目的 通过对难治性抑郁症(TRD)患者不同阶段血清脑源性神经营养因子(BDNF)水平的动态监测,探讨TRD与BDNF的关系.方法 26例TRD患者分别在治疗前、急性治疗期、巩固期、维持期四个阶段进行汉密尔顿抑郁量表(HAMD)评定,用酶联免疫吸附法(ELISA)测定其血清BDNF含量.并于治疗前与非难治性抑郁症(TNRD)患者及正常体检者各30例进行对照.结果 治疗前,TRD组与TNRD组HAMD评分均较正常组显著升高(P＜0.01);血清BDNF水平则较正常组显著降低(P＜0.01),其中TRD组比TNRD组下降更明显(P＜0.01),相关性分析表明血清BDNF水平与HAMD评分呈明显负相关(r=-0.667,P＜0.01);治疗后,TRD巩固期和维持期血清BDNF水平较治疗前和急性治疗期均有明显升高(P＜0.01),同时HAMD评分也较治疗前和急性治疗期减少(P＜0.01),其中维持期减少更为明显(P＜0.01).结论 血清BDNF水平低下可能是TRD的病理机制之一,有效的抗抑郁药物治疗机制之一可能是通过提高BDNF水平而起作用的,BDNF可以作为反映TRD疗效的生物学指标.     

Correlation of brain-derived neurotrophic factor to cognitive impairment following traumatic brain injury in rats

BACKGROUND: In vitro and in vivo studies have confirmed that brain-derived neurotrophic factor (BDNF) can promote survival and differentiation of cholinergic, dopaminergic and motor neurons, and axonal regeneration. BDNF has neuroprotective effects on the nervous system. OBJECTIVE: To explore changes in BDNF expression and cognitive function in rats after brain injury DESIGN, TIME AND SETTING: The neuropathology experiment was performed at the Second Research Room, Department of Neurosurgery, Fujian Medical University (China) from July 2007 to July 2008. MATERIALS: A total of 72 healthy, male, Sprague Dawley, rats were selected for this study. METHODS: Rat models of mild and moderate traumatic brain injury were created by percussion, according to Feeney's method (n = 24, each group). A bone window was made in rats from the sham operation group (n = 24), but no attack was conducted. MAIN OUTCOME MEASURES: At days 1,2, 4 and 7 following injury, BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was examined by immunohistochemistry (streptavidin-biotin-peroxidase complex method). Changes in rat cognitive function were assessed by the walking test, balance-beam test and memory function detection. RESULTS: Cognitive impairment was aggravated at day 2, and recovered to normal at days 3 and 7 in rats from the mild and moderate traumatic brain injury groups. BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was increased at 1 day, decreased at day 2, and then gradually increased in the mild and moderate traumatic brain injury groups. BDNF expression was greater in rats from the moderate traumatic brain injury group than in the sham operation and mild traumatic brain injury groups (P < 0.05). CONCLUSION: BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain is correlated to cognitive impairment after traumatic brain injury. BDNF has a protective effect on cognitive function in rats following injury     

Brain-derived neurotrophic factor and substantia nigra dopaminergic neurons in Parkinson''s disease

BACKGROUND:Parkinson's disease (PD) is a chronic, progressive neurodegenerative central nervous system disease which occurs in the substantia nigra-corpus striatum system. The main pathological feature of PD is selective dopaminergic neuronal loss with distinctive Lewy bodies in populations of surviving dopaminergic neurons. In the clinical and neuropathological diagnosis of PD, brain-derived neurotrophic factor mRNA expression in the substantia nigra pars compacta is reduced by 70%, and surviving dopaminergic neurons in the PD substantia nigra pars compacta express less brain-derived neurotrophic factor (BDNF) mRNA (20%) than their normal counterparts. In recent years, knowledge surrounding the relationship between neurotrophic factors and PD has increased, and detailed pathogenesis of the role of neurotrophic factors in PD becomes more important.     

Correlation of brain-derived neurotrophic factor to cognitive impairment following traumatic brain injury in rats**☆

BACKGROUND： In vitro and in vivo studies have confirmed that brain-derived neurotrophic factor （BDNF） can promote survival and differentiation of cholinergic, dopaminergic and motor neurons, and axonal regeneration. BDNF has neuroprotective effects on the nervous system. OBJECTIVE： To explore changes in BDNF expression and cognitive function in rats after brain injury. DESIGN, TIME AND SETTING： The neuropathology experiment was performed at the Second Research Room, Department of Neurosurgery, Fujian Medical University （China） from July 2007 to July 2008. MATERIALS： A total of 72 healthy, male, Sprague Dawley, rats were selected for this study. METHODS： Rat models of mild and moderate traumatic brain injury were created by percussion, according to Feeney＇s method （n = 24, each group）. A bone window was made in rats from the sham operation group （n = 24）, but no attack was conducted. MAIN OUTCOME MEASURES： At days 1, 2, 4 and 7 following injury, BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was examined by immunohistochemistry （streptavidin-biotin-peroxidase complex method）. Changes in rat cognitive function were assessed by the walking test, balance-beam test and memory function detection. RESULTS： Cognitive impairment was aggravated at day 2, and recovered to normal at days 3 and 7 in rats from the mild and moderate traumatic brain injury groups. BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was increased at 1 day, decreased at day 2, and then gradually increased in the mild and moderate traumatic brain injury groups. BDNF expression was greater in rats from the moderate traumatic brain injury group than in the sham operation and mild traumatic brain injury groups （P 〈 0.05）. CONCLUSION： BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain is correlated to cognitive impairment after traumatic brain injury. BDNF has a protective effect on cognitive function in rats following i     

立体定向下核团毁损术及脑深部电刺激术治疗难治性强迫症

目的探讨MRI定位下核团毁损术及脑深部电刺激术治疗难治性强迫症的疗效。方法应用MRI定位下射频热凝核团毁损术及脑深部电刺激术治疗难治性强迫症49例，其中30例行双侧内囊前肢毁损术，13例行双侧扣带回加双侧内囊前肢毁损术,6例行右侧伏隔核脑深部电刺激术加对侧内囊前肢毁损术。手术前后应用YALE-BROWN强迫症状量表、汉密尔顿抑郁量表、汉密尔顿焦虑量表对手术效果进行评价。结果术后6个月均获随访，其中临床痊愈28例，显著改善9例，轻度改善7例，无明显变化5例。22例术后早期出现一过性并发症，均在术后2周内恢复。术后焦虑，强迫，抑郁症状量表分数均明显下降（P〈0．01）。结论MRI定位下核团毁损术及脑深部电刺激术治疗难治性强迫症有显著疗效，并发症较轻，可以显著改善病人强迫、焦虑、抑郁症状。     

Brain-derived neurotrophic factor and substantia nigra dopaminergic neurons in Parkinson’s disease☆

Parkinson＇s disease （PD） is a chronic, progressive neurodegenerative central nervous system disease which occurs in the substantia nigra-corpus striatum system. The main pathological feature of PD is selective dopaminergic neuronal loss with distinctive Lewy bodies in populations of surviving dopaminergic neurons. In the clinical and neuropathological diagnosis of PD, brain-derived neurotrophic factor mRNA expression in the substantia nigra pars compacta is reduced by 70%, and surviving dopaminergic neurons in the PD substantia nigra pars compacta express less brain-derived neurotrophic factor （BDNF） mRNA （20%） than their normal counterparts. In recent years, knowledge surrounding the relationship between neurotrophic factors and PD has increased, and detailed pathogenesis of the role of neurotrophic factors in PD becomes more important.     

Role of brain-derived neurotrophic factor and neuronal nitric oxide synthase in stress-induced depression*★

BACKGROUND： Accumulated evidence indicates an important role for hippocampal dendrite atrophy in development of depression, while brain-derived neurotrophic factor （BDNF） participates in hippocampal dendrite growth. OBJECTIVE： To discuss the role of BDNF and neuronal nitric oxide synthase （nNOS） in chronic and unpredictable stress-induced depression and the pathogenesis of depression. DESIGN, TIME AND SETTING： Randomized, controlled animal experiment. The experiment was carded out from October 2006 to May 2007 at the Department of Animal Physiology, College of Life Science, Shaanxi Normal University. MATERIALS： Thirty-seven male Sprague-Dawley rats weighing 250-300 g at the beginning of the experiment were obtained from Shaanxi Provincial Institute of Traditional Chinese Medicine （Xi＇an, China）. BDNF antibody and nNOS antibody were provided by Santa Cruz （USA）. K252a （BDNF inhibitor） and 7-NI （nNOS inhibitor） were provided by Sigma （USA）. METHODS： Animals were randomly divided into five groups： Control group, chronic unpredicted mild stress （CUMS） group, K252a group, K252a＋7-NI group and 7-NI＋CUMS group. While the Control, K252a and K252a＋7-NI groups of rats not subjected to stress had free access to food and water, other groups of rats were subjected to nine stressors randomly applied for 21 days, with each stressor applied 2-3 times. On days 1, 7, 14 and 21 during CUMS, rats received microinjection of 1 μL of physiological saline in the Control and CUMS groups, 1 ~ L of K252a in the K252a group, 1 μL of K252a and 7-NI in the K252a＋7-NI group, and 1 μL of 7-NI in the 7-NI＋CUMS group. We observed a variety of alterations in sucrose preference, body weight change, open field test and forced swimming test, and observed the expression of BDNF and nNOS in rat hippocampus by immunohistochemistry; MAIN OUTCOME MEASURES： ① A variety.of behavioral alterations of rats; ② The expression of BDNF and nNOS in rat hippocampus. RESULTS： Compared with the Control     

A connectomic analysis of deep brain stimulation for treatment-resistant depression

ObjectiveDeep brain stimulation (DBS) has been used as a treatment of last resort for treatment-resistant depression (TRD) for more than a decade. Many DBS targets have been proposed and tested clinically, but the underlying circuit mechanisms remain unclear. Uncovering white matter tracts (WMT) activated by DBS targets may provide crucial information about the circuit substrates mediating DBS efficacy in ameliorating TRD.MethodsWe performed probabilistic tractography using diffusion magnetic resonance imaging datas from 100 healthy volunteers in Human Connectome Project datasets to analyze the structural connectivity patterns of stimulation targeting currently-used DBS target for TRD. We generated mean and binary fiber distribution maps and calculated the numbers of WMT streamlines in the dataset.ResultsProbabilistic tracking results revealed that activation of distinct DBS targets demonstrated modulation of overlapping but considerably distinct pathways. DBS targets were categorized into 4 groups: Cortical, Striatal, Thalamic, and Medial Forebrain Bundle according to their main modulated WMT and brain areas. Our data also revealed that Brodmann area 10 and amygdala are hub structures that are associated with all DBS targets.ConclusionsOur results together suggest that the distinct mechanism of DBS targets implies individualized target selection and formulation in the future of DBS treatment for TRD. The modulation of Brodmann area 10 and amygdala may be critical for the efficacy of DBS-mediated treatment of TRD.     

艾司西酞普兰对抑郁模型大鼠行为学及脑脊液、血清脑源性神经营养因子水平的影响

目的:探讨艾司西酞普兰对慢性应激致抑郁模型大鼠行为学及脑脊液、血清脑源性神经营养因子(BDNF)水平的影响。方法:将Sprague Dawley(SD)雄性大鼠随机分为应激组和非应激组,应激组给予慢性不可预知温和应激(CUMS)刺激8周;刺激4周后根据行为学评估[包括强迫游泳实验(FST)、蔗糖水偏爱实验(SPT)、旷场实验(OFT)]及体质量将抑郁行为大鼠随机分为抑郁模型组和抑郁给药组,非应激组随机分为正常对照组和正常给药组,各组6只。第5周起给予两给药组艾司西酞普兰(10 mg/kg·d)腹腔注射4周。刺激及给药结束后对各组大鼠再次行为学评估并检测脑脊液、血清BDNF水平。结果:CUMS 4周后,与非应激组相比,应激组FST中不动时间显著延长,SPT显著降低,OFT中路程及站立次数显著减少,体质量显著降低(P均0.01);药物干预4周后,与抑郁模型组相比,抑郁给药组FST中不动时间显著缩短,SPT及OFT中总路程显著增加(P均0.05);脑脊液、血清BDNF水平抑郁模型组显著低于正常对照组,抑郁给药显著高于抑郁模型组(P0.05或P0.01)。结论:艾司西酞普兰可改善抑郁大鼠的抑郁行为,提高脑脊液及血清BDNF水平。     

丘脑底核深部电刺激对帕金森病患者抑郁及焦虑的影响

目的探讨丘脑底核(STN)深部电刺激(DBS)手术对帕金森病(PD)患者抑郁及焦虑的影响。方法41例接受STNDBS治疗的PD患者进行神经心理评估,分别于术前1周及术后12个月应用HY分期、统一PD评定量表运动检查部分(UPDRSⅢ)、医院焦虑和抑郁量表(HADS)及PD生活质量问卷(PDQ39)评价其病情、运动状况、情绪及生活质量,并进行统计学分析。结果术后患者UPDRSⅢ、HADS及PDQ39评分较术前极显著改善(均P<0.001),HY分期在“开”及“关”状态均明显改善(P<0.05,P<0.001);Spearman相关性检验提示HADS抑郁评分与PDQ39中情绪状态、羞耻感及总评分变化正相关(r分别为0.35、0.37、0.34,均P<0.05),与HY分期、UPDRSⅢ不相关。HADS焦虑评分与其均不相关。结论STNDBS能改善PD患者的情绪,特别是抑郁状态,进而改善其生活质量。     

脑深部电刺激治疗对帕金森病患者认知功能、抑郁和焦虑的影响

目的探讨双侧丘脑底核脑深部电刺激治疗(STN-DBS)对帕金森病(PD)患者认知功能和抑郁、焦虑状态的影响。方法连续收集16例拟行双侧STN-DBS的PD患者为实验组,在术前1周、术后1月和术后3月行认知功能、抑郁和焦虑状态评估。同期在门诊收集16例优化药物治疗的PD患者为对照组,在相同时间点行同样的神经心理量表评估。结果实验组患者的Mo CA评分与术前(20.69±4.33)相比,在术后1月(19.81±4.34)及术后3月(19.44±5.35)均有下降趋势,但差异无统计学意义(P0.05)。实验组患者的抑郁症状与术前(23.56±14.60)相比,在术后1月(11.94±6.16)及术后3月(7.38±5.18)有明显改善(P0.05)。实验组患者的焦虑症状与术前(22.13±6.11)相比,在术后1月(15.13±5.62)及术后3月(8.00±6.76)有明显改善(P0.05)。抑郁焦虑的改善在任何时期均与UPDRS-Ⅲ无相关性(P0.05)。结论双侧STN-DBS治疗在术后3月时并不影响PD患者的总体认知功能,但各个认知域的改变需要更为详细的神经心理量表评估;双侧STN-DBS治疗在短期内可以显著改善PD患者的抑郁和焦虑症状,且抑郁和焦虑症状的改善与STN-DBS治疗后运动症状的改善无关。     

帕金森病脑深部刺激治疗对认知和抑郁状态影响的队列研究

目的探讨帕金森病(PD)丘脑底核(STN)脑深部刺激治疗(DBS)对认知和抑郁状态的影响。方法连续的27例PD患者接受丘脑底核脑深部刺激治疗(STN-DBS)手术治疗,术前1周及术后6个月对认知和抑郁状态进行评估。结果术后6个月认知功能与术前认知、运动症状改善程度正相关。术后抑郁评分的改善程度与术前抑郁评分和运动症状改善程度正相关。结论在严格筛选手术适应证的前提下,STN-DBS可能对部分患者的认知功能有改善作用,并且不加重抑郁状态。