基于体素的形态学MRI观察未经药物治疗的强迫症患者脑灰质结构改变

目的 探查未经药物治疗的强迫症患者脑灰质结构存在异常的区域,并探讨脑灰质体积改变与临床症状之间的关系.方法 用基于体素的形态学方法(voxel-based morphometry,VBM),对比分析21例未经药物治疗的强迫症患者和21例年龄、性别及受教育程度相匹配的正常对照者脑灰质体积存在差异的脑区,并采用耶鲁-布郎量表(Y-BOCS)、汉密尔顿抑郁量表(HAMD)及汉密尔顿焦虑量表(HAMA)评估临床症状.结果 强迫症患者与正常对照者相比脑灰质结构存在明显萎缩的区域主要位于双侧眶额叶、前扣带回、右侧丘脑以及右侧小脑(P＜0.05,FDR校正),患者左侧眶额叶的灰质体积与耶鲁布朗量表评分之间存在负相关(r=-0.63,P＜0.01).结论“皮质-纹状体-丘脑-皮质”环路的结构异常在强迫症的发病机制中起着重要作用,同时表明环路外小脑等结构的异常也可能参与了强迫症的病理生理学进程.     

Cerebral blood flow and gray matter volume covariance patterns of cognition in aging

Advancing age results in altered cognitive and neuroimaging‐derived markers of neural integrity. Whether cognitive changes are the result of variations in brain measures remains unclear and relating the two across the lifespan poses a unique set of problems. It must be determined whether statistical associations between cognitive and brain measures truly exist and are not epiphenomenal due solely to their shared relationships with age. The purpose of this study was to determine whether cerebral blood flow (CBF) and gray matter volume (GMV) measures make unique and better predictions of cognition than age alone. Multivariate analyses identified brain‐wide covariance patterns from 35 healthy young and 23 healthy older adults using MRI‐derived measures of CBF and GMV related to three cognitive composite scores (i.e., memory, fluid ability, and speed/attention). These brain‐cognitive relationships were consistent across the age range, and not the result of epiphenomenal associations with age and each imaging modality provided its own unique information. The CBF and GMV patterns each accounted for unique aspects of cognition and accounted for nearly all the age‐related variance in the cognitive composite scores. The findings suggest that measures derived from multiple imaging modalities explain larger amounts of variance in cognition providing a more complete understanding of the aging brain. Hum Brain Mapp 34:3267–3279, 2013. © 2012 Wiley Periodicals, Inc.     

Differential distribution of parvalbumin- and calbindin-D28K-immunoreactive neurons in the rat periaqueductal gray matter and their colocalization with enzymes producing nitric oxide

The distribution, colocalization with enzymes producing nitric oxide (NO), and the synaptic organization of neurons containing two calcium-binding proteins (CaBPs) – parvalbumin (Parv) and calbindin-D28K (Calb) – were investigated in the rat periaqueductal gray matter (PAG). Parv-immunopositive (Parv_IP) neurons were detected in the mesencephalic nucleus and rarely in the PAG. Calb_IP neurons were found both in the dorsolateral (PAG-dl) and ventrolateral PAG (PAG-vl); their size ranged from 112.96 μm² (PAG-dl) to 125.13 μm² (PAG-vl). Ultrastructurally Parv and Calb immunoreactivity was mostly found in dendritic profiles. Axon terminals containing each of the two CaBPs formed symmetric synapses. Moreover both Parv and Calb were used to label a subpopulation of NO-producing neurons. Colocalization was investigated using two protocols: (i) a combination of Calb and Parv immunocytochemistry (Icc) with nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry (Hi) and (ii) neuronal NO synthase-Icc (nNOS) (immunofluorescence).Both techniques demonstrated a complete lack of colocalization of Parv and NADPH-d/nNOS in PAG neurons.Double-labeled (DL) neurons (Calb-NADPH-d; Calb-nNOS) were detected in PAG-dl. NADPH-d-Hi/Calb-Icc indicated that 41–47% of NADPH-d-positive neurons contained Calb, whereas 17–23% of Calb_IP cells contained NADPH-d. Two-color immunofluorescence revealed that 53–66% of nNOS_IP cells colocalized with Calb and 24–34% of Calb_IP neurons contained nNOS. DL neuron size was 104.44 μm²; neurons labeled only with NADPH-d or Calb measured 89.793 μm² and 113.48 μm², respectively.Together with previous findings (Barbaresi et al. [2012]) these data suggest that:

• (i) PAG-dl and PAG-vl contain fast CaBPs, (ii) a high degree of heterogeneity exists in PAG-dl, (iii) two subpopulations of NO-producing neurons containing distinct CaBPs are found in PAG-dl.

Therefore the important aspect of the PAG intrinsic organization emerging from this and previous double-labeling studies is the chemical diversity of NO-synthesizing neurons, which is likely related to the different functions in which these neurons are involved.     

Relaxin‐3 innervation of the intergeniculate leaflet of the rat thalamus – neuronal tract‐tracing and in vitro electrophysiological studies

Behavioural state is controlled by a range of neural systems that are sensitive to internal and external stimuli. The relaxin‐3 and relaxin family peptide receptor 3 (RXFP3) system has emerged as a putative ascending arousal network with putative involvement in regulation of stress responses, neuroendocrine control, feeding and metabolism, circadian activity and cognition. Relaxin‐3/γ‐aminobutyric acid neuron populations have been identified in the nucleus incertus, pontine raphe nucleus, periaqueductal grey (PAG) and an area dorsal to the substantia nigra. Relaxin‐3‐positive fibres/terminals densely innervate arousal‐related structures in the brainstem, hypothalamus and limbic forebrain, but the functional significance of the heterogeneous relaxin‐3 neuron distribution and its inputs to specific brain areas are unclear. Therefore, in this study, we used neuronal tract‐tracing and immunofluorescence staining to explore the source of the dense relaxin‐3 innervation of the intergeniculate leaflet (IGL) of the thalamus, a component of the neural circadian timing system. Confocal microscopy analysis revealed that relaxin‐3‐positive neurons retrogradely labelled from the IGL were predominantly present in the PAG and these neurons expressed corticotropin‐releasing factor receptor‐like immunoreactivity. Subsequently, whole‐cell patch‐clamp recordings revealed heterogeneous effects of RXFP3 activation in the IGL by the RXFP3 agonist, relaxin‐3 B‐chain/insulin‐like peptide‐5 A‐chain (R3/I5). Identified, neuropeptide Y‐positive IGL neurons, known to influence suprachiasmatic nucleus activity, were excited by R3/I5, whereas neurons of unidentified neurotransmitter content were either depolarized or displayed a decrease in action potential firing and/or membrane potential hyperpolarization. Our data identify a PAG to IGL relaxin‐3/RXFP3 pathway that might convey stress‐related information to key elements of the circadian system and influence behavioural state rhythmicity.     

A longitudinal study of age‐ and gender‐related annual rate of volume changes in regional gray matter in healthy adults

The aim of this study was to analyze correlations among the annual rate of gray matter volume change, age, gender, and cerebrovascular risk factors in 381 healthy community‐dwelling subjects with a large age range by applying a longitudinal design over 6 years using brain magnetic resonance images (MRIs). Brain MRI data were processed with voxel‐based morphometry using a custom template by applying diffeomorphic anatomical registration using the exponentiated lie algebra procedure. The annual rate of regional gray matter volume change showed significant positive correlations with age in several regions, including the bilateral temporal pole, caudate nucleus, ventral and dorsolateral prefrontal cortices, insula, hippocampus, and temporoparietal cortex, whereas significant negative correlations with age were observed in several regions including the bilateral cingulate gyri and anterior lobe of the cerebellum. Additionally, a significant age‐by‐gender interaction was found for the annual rate of regional gray matter volume change in the bilateral hippocampus. No significant correlations were observed between the annual rate of regional gray matter volume change and body mass index or systolic blood pressure. A significant positive correlation between the annual rate of gray matter volume change and age indicates that the region shows not linear but accelerated gray matter loss with age. Therefore, evaluating the annual rate of the gray matter volume change with age in healthy subjects is important in understanding how gray matter volume changes with aging in each brain region and in anticipating what cognitive functions are likely to show accelerated decline with aging. Hum Brain Mapp 34:2292–2301, 2013. © 2012 Wiley Periodicals, Inc.     

续断“发汗”前后HPLC指纹图谱与细胞增殖分化药效的谱效关系研究

目的研究续断"发汗"前后水煎液HPLC指纹图谱与促进大鼠成骨细胞、人成骨样MG-63细胞增殖药效的谱效关系,寻找续断发汗前后发挥药效的物质基础,为明确"发汗"对药效的影响提供依据。方法采用DAD检测器建立续断"发汗"前后水煎液的HPLC指纹图谱,采用灰色关联度分析法建立其谱效关系。结果 14和4号峰代表的化学成分与成骨细胞的增殖分化及MG-63细胞的增殖都具有较高的关联度,关联度均在0.7以上。与成骨细胞增殖、MG-63细胞增殖、碱性磷酸酶(ALP)活性3个药效指标关联度排序比较靠前的特征峰有14、4、6、16、13、11、5号峰。结合前期研究推断,这些峰可能为川续断皂苷VI、绿原酸、马钱苷、川续断皂苷IV同分异构体、川续断皂苷X、异绿原酸C、咖啡酸。结论川续断皂苷VI、绿原酸、马钱苷、川续断皂苷IV同分异构体、川续断皂苷X、异绿原酸C、咖啡酸可能是续断"发汗"前后影响细胞增殖分化作用的主要物质基础,进而影响其药效。     

The Role of Platelets and ε‐Aminocaproic Acid in Arthrogryposis,Renal Dysfunction,and Cholestasis (ARC) Syndrome Associated Hemorrhage

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is a rare disorder associated with platelet abnormalities resembling gray platelet syndrome. Affected patients have normal platelet numbers but abnormal morphology and function. Bleeding symptomatology ranges from postprocedural to spontaneous life‐threatening hemorrhage. We report a patient with ARC syndrome and compound heterozygous mutations in VPS33B (vacuolar protein sorting 33B) who presented with significant bleeding requiring numerous admissions and transfusions. She was treated with prophylactic platelet transfusions and ε‐aminocaproic acid. This was well‐tolerated and significantly decreased transfusion requirements and admissions for bleeding. Our experience provides support for consideration of prophylactic measures in these patients as well as the possibility of using prophylaxis in related disorders.     

Three-dimensional ultrasonographic placental volume in gestational diabetes mellitus

Objectives: We aimed to evaluate the placental volume and placental mean gray value in gestational diabetes mellitus (GDM) and healthy placentas using three-dimensional (3D) ultrasound and Virtual Organ Computer-aided AnaLysis (VOCAL).

Methods: This case-control prospective study consisted of 39 singleton pregnancies complicated by GDM and 42 healthy singleton pregnancies matched for gestational age, maternal age and parity. Placental volume and placental volumetric mean gray values were evaluated. The placental volume (cm³) was analyzed using the VOCAL imaging analysis program and 3D histogram was used to calculate the volumetric mean gray value (%).

Results: Placental volume was significantly larger in GDM (411.59?±?170.82 versus 343.86?±?128.94?cm³; p?=?0.046). There was no significant difference in mean gray value between GDM and healthy placentas (36.65?±?7.02 versus 38.71?±?7.91, respectively; p?=?0.277). Placental volume was significantly correlated with gestational week (r?=?0.219, p?=?0.035) and parity (r?=?0.228, p?=?0.048). There was negative significant relation between placental volume and umbilical artery systolic/diastolic ratio, pulsatility index and resistance index (r?=??0.278, p?=?0.007; r?=??0.315, p?=?0.002; r?=??0.322, p?=?0.001, respectively).

Conclusions: Placental volume increases significantly in GDM, whereas mean gray values do not alter significantly. These data may reflect the placental changes in GDM placentas that may help to understand the pathophysiology better.     

GABAergic processes in the mesencephalic tegmentum modulate the occurrence of active (rapid eye movement) sleep in guinea pigs

The ventrolateral subdivision of the periaqueductal gray (vlPAG) and the adjacent dorsal mesencephalic reticular formation (dMRF) are involved in the modulation of active (rapid eye movement) sleep (AS). In order to determine the effects on AS of the suppression of neuronal activity in these regions, muscimol, a GABA receptor A (GABA(A)) receptor agonist, and bicuculline, a GABA(A) receptor antagonist, were microinjected bilaterally in guinea pigs and the states of sleep and wakefulness were examined. The main effect of muscimol was an increase in AS; this increase occurred in conjunction with a reduction in the time spent in wakefulness. The powerful effect of muscimol was striking especially when considering the small amount of naturally-occurring AS that is present in this species. Additional observable effects that were induced by muscimol were: 1) long lasting episodes of hypotonia/atonia during wakefulness and quiet sleep that included a lack of extensor tone in the hind limbs, and 2) frequently occurring cortical spindles, similar to those observed during naturally-occurring quiet sleep (sleep spindles), that were present during wakefulness. Conversely, bilateral microinjections of bicuculline induced a prolonged state of wakefulness and blocked the effect of subsequent injections of muscimol. These data suggest that endogenous GABA acts on GABA(A) receptors within the vlPAG and dMRF to promote AS in the guinea pig.