Neuronal injury and brain-derived neurotrophic factor expression in a rat model of amygdala kindling seizures Differences in brain regions and kindling courses

BACKGROUND：Studies have demonstrated that brain-derived neurotrophic factor （BDNF） has a dual effect on epilepsy. However, the relationship between epilepsy-induced brain injury and BDNF remains poorly understood.OBJECTIVE：According to ultrastructural and molecular parameters, to detect the degree of neuronal injury and BDNF expression changes at different brain regions and different kindling times to determine the effects of BDNF on epilepsy-induced brain injury.DESIGN, TIME AND SETTING：A randomized, controlled, animal experiment based on neuropathology and molecular biology was performed at the Department of Physiology and Department of Pathology, Basic Medical College of Jilin University in 2003.MATERIALS：UltraSensitiveTM SP kit for immunohistochemistry （Fuzhou Maxim Biotechnology, China）, BDNF antibody （concentrated type, Wuhan Boster Biological Technology, China）, JEM-1000SX transmission electron microscopy （JEOL, Japan）, and BH-2 light microscope （Olympus, Japan） were used in the present study.METHODS：Wistar rats were randomly assigned to control （n = 6）, sham-surgery （n = 6）, and model （n = 60） groups. The control group rats were not treated; an electrode was embedded into the amygdala in rats from the sham-surgery and model groups; an amygdala kindling epilepsy model was established in the model group.MAIN OUTCOME MEASURES：Pathological changes in the temporal lobe and hippocampus were observed by light and electron microscopy at 1, 3, 7, 14, and 21 days following kindling, and BDNF expression in the various brain regions was determined by immunohistochemistry.RESULTS：In the model group, temporal lobe cortical and hippocampal neurons were swollen and the nuclei were laterally deviated. There were also some apoptotic neurons 3 days after kindling. The nucleoli disappeared and the nuclei appeared broken or lysed, as well as slight microglia hyperplasia, at 7 days. Electron microscopic observation displayed chromatin aggregation in the nuclei and slight mitochondrion swelling 3 days after kindling. Injury changes were aggravated at 7 days, characterized by broken cytoplasmic membrane and pyknosis. With the development of seizure, the number of BDNF-positive neurons in the hippocampus and temporal lobe increased and peaked at 7 days. Moreover, hippocampal and cortical temporal lobe injury continued. Following termination of electrical stimulation after 7 days of kindling, BDNF expression decreased, but continued to be expressed, up to 21 days of kindling. In addition, the number of temporal and hippocampal BDNF-positive neurons was greater than the control group.CONCLUSION：Brain injury and BDNF expression peaked at 7 days after kindling, and hippocampal changes were significant.

Susceptibility-weighted imaging is suitable for evaluating signal strength in different brain regions of a rabbit model of acute hemorrhagic anemia

Acute hemorrhagic anemia can decrease blood flow and oxygen supply to brain, and affect its physiological function. While detecting changes in brain function in patients with acute hemorrhagic anemia is helpful for preventing neurological complications and evaluating therapeutic effects, clinical changes in the nervous systems of these patients have not received much attention. In part, this is because current techniques can only indirectly detect changes in brain function following onset of anemia, which leads to lags between real changes in brain function and their detection.

Exploring the Abnormal Brain Regions and Abnormal Functional Connections in SZ by Multiple Hypothesis Testing Technique

Schizophrenia(SZ)is one of the most common mental diseases.Its main characteristics are abnormal social behavior and inability to correctly understand real things.In recent years,the magnetic resonance imaging(MRI)technique has been popularly utilized to study SZ.However,it is still a great challenge to reveal the essential information contained in the MRI data.In this paper,we proposed a biomarker selection approach based on the multiple hypothesis testing techniques to explore the difference between SZ and healthy controls by using both functional and structural MRI data,in which biomarkers represent both abnormal brain functional connectivity and abnormal brain regions.By implementing the biomarker selection approach,six abnormal brain regions and twenty-three abnormal functional connectivity in the brains of SZ are explored.It is discovered that compared with healthy controls,the significantly reduced gray matter volumes are mainly distributed in the limbic lobe and the basal ganglia,and the significantly increased gray matter volumes are distributed in the frontal gyrus.Meanwhile,it is revealed that the significantly strengthened connections are those between the middle frontal gyrus and the superior occipital gyrus,the superior occipital gyrus and the middle occipital gyrus as well as the middle occipital gyrus and the fusiform gyrus,and the rest connections are significantly weakened.

Chronic effect of olive oil on some neurotransmitter contents in different brain regions and physiological, histological structure of liver and kidney of male albino rats

Olive oil is an important source of mono-unsaturated fat and a prime component of the Mediterranean diet. The beneficial health effects of olive oil are due to both its high content of mono-unsaturated fatty acids and its high content of anti-oxidative substances. The objective of this study was to investigate the basis for the epidemiological information relating to the health benefits associated with the consumption of ex-tra-virgin olive oil (EVOO). The effect of olive oil on norepinephrine (NE), dopamine (DA), serotonin (5-HT) and gamm-aminobutyric acid (GABA) con-tents in different brain regions and histological structure of liver and kindey of male albino rats was studied. The chronic administration of olive oil (7.5 mg/kg body wt.) caused a significant increase in norepinephrine (NE), dopamine (DA) , serotonin (5-HT) and gamm-aminobutyric acid (GABA) con-tent in different brain regions (Cerebellum, striatum, cerebral cortex, hypothalamus, brain steam and hip-pocampus) of male albino rats. The increase in NE, DA, 5-HT, and GABA content in the different CNS areas of male albino rat may be due to the inhibition of Ca2+/calmodulin binding which plays an important role in the release of these neurotransmitters. The results, also, revealed that urea and creatinne con-centrations in rats with oral administration with olive oil were decreased. Meanwhile, the activities of the enzymes AsT, AlT and ALP were elevated. The pre-sent results indicated that there is no change in tis-sues of kidney after treated with virgin olive oil. Olive oil may potentially be safe for use as a sedative drug. improvement also led to the reductions in risk of Alzheimer’s and Parkinson’s diseases.

Identification of differential brain regions in MCI progression via clustering-evolutionary weighted SVM ensemble algorithm

Mild cognitive impairment(MCI)as the potential sign of serious cognitive decline could be divided into two stages,i.e.,late MCI(LMCI)and early MCI(EMCI).Although the different cognitive states in the MCI progression have been clinically defined,effective and accurate identification of differences in neuroimaging data between these stages still needs to be further studied.In this paper,a new method of clustering-evolutionary weighted support vector machine ensemble(CEWSVME)is presented to investigate the alterations from cognitively normal(CN)to EMCI to LMCI.The CEWSVME mainly includes two steps.The first step is to build multiple SVM classifiers by randomly selecting samples and features.The second step is to introduce the idea of clustering evolution to eliminate inefficient and highly similar SVMs,thereby improving the final classification performances.Additionally,we extracted the optimal features to detect the differential brain regions in MCI progression,and confirmed that these differential brain regions changed dynamically with the development of MCI.More exactly,this study found that some brain regions only have durative effects on MCI progression,such as parahippocampal gyrus,posterior cingulate gyrus and amygdala,while the superior temporal gyrus and the middle temporal gyrus have periodic effects on the progression.Our work contributes to understanding the pathogenesis of MCI and provide the guidance for its timely diagnosis.

Altered spontaneous brain activity patterns in hypertensive retinopathy using fractional amplitude of low-frequency fluctuations:a functional magnetic resonance imaging study

AIM:To study functional brain abnormalities in patients with hypertensive retinopathy(HR)and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations(fALFFs)method.METHODS:Twenty HR patients and 20 healthy controls(HCs)were respectively recruited.The age,gender,and educational background characteristics of the two groups were similar.After functional magnetic resonance imaging(fMRI)scanning,the subjects’spontaneous brain activity was evaluated with the fALFF method.Receiver operating characteristic(ROC)curve analysis was used to classify the data.Further,we used Pearson’s correlation analysis to explore the relationship between fALFF values in specific brain regions and clinical behaviors in patients with HR.RESULTS:The brain areas of the HR group with lower fALFF values than HCs were the right orbital part of the middle frontal gyrus(RO-MFG)and right lingual gyrus.In contrast,the values of fALFFs in the left middle temporal gyrus(MTG),left superior temporal pole(STP),left middle frontal gyrus(MFG),left superior marginal gyrus(SMG),left superior parietal lobule(SPL),and right supplementary motor area(SMA)were higher in the HR group.The results of a t-test showed that the average values of fALFFs were statistically significantly different in the HR group and HC group(P<0.001).The fALFF values of the left middle frontal gyrus in HR patients were positively correlated with anxiety scores(r=0.9232;P<0.0001)and depression scores(r=0.9682;P<0.0001).CONCLUSION:fALFF values in multiple brain regions of HR patients are abnormal,suggesting that these brain regions in HR patients may be dysfunctional,which may help to reveal the pathophysiological mechanisms of HR.

Functional connectivity of paired default mode network subregions in patients with eye trauma

AIM:To study functional brain abnormalities in patients with eye trauma(ET)and to discuss the pathophysiological mechanisms of ET.METHODS:Totally 31 ET patients and 31 healthy controls(HCs)were recruited.The age,gender,and educational background characteristics of the two groups were similar.After functional magnetic resonance imaging(fMRI)scanning,the subjects’spontaneous brain activity was evaluated with the functional connectivity(FC)method.Receiver operating characteristic(ROC)curve analysis was used to classify the data.Pearson’s correlation analysis was used to explore the relationship between FC values in specific brain regions and clinical behaviors in patients with ET.RESULTS:Significantly increased FC between several regions was identified including the medial prefrontal cortex(MPFC)and left hippocampus formations(HF),the MPFC and left inferior parietal lobule(IPL),the left IPL and left medial temporal lobe(MTL),the left IPL and right MTL,and the right IPL and left MTL.No decreased region-to-region connectivity was detected in default mode network(DMN)sub-regions in patients with ET.Compared with HCs,ET patients exhibited significantly increased FC between several paired DMN regions,as follows:posterior cingulate cortex(PCC)and right HF(HF.R,t=2.196,P=0.032),right inferior parietal cortices(IPC.R)and left MTL(MTL.L,t=2.243,P=0.029),and right MTL(MTL.R)and HF.R(t=2.236,P=0.029).CONCLUSION:FC values in multiple brain regions of ET patients are abnormal,suggesting that these brain regions in ET patients may be dysfunctional,which may help to reveal the pathophysiological mechanisms of ET.

Differential Neutrophil Infiltration Contributes to Regional Differences in Brain Infiammation in the Substantia Nigra Pars Compacta and Cortex

脑的炎症反应是神经退行性疾病的危险因素之一。有趣的是,黑质密部(SNpc)严重的炎性反应会加速帕金森病的发作和进展。本研究通过比较SNpc与皮质的炎性过程来检测SNpc严重炎性反应的潜在机制。在完整的脑组织中,SNpc和皮质的CD11b+小胶质细胞密度是相似的。但是,脂多糖注射可增加SNpc的CD11b+细胞数目,而不能增加皮质中的。以前作者曾报道内毒素注射之后,黑质密部有CD11b和MPO双阳性的中性粒细胞浸润(GLIA55:1577-1588)。值得注意的是,MPO+中性粒细胞数量在SNpc中显著增加,而在皮质中只有轻微提高。中性粒细胞浸润的范围与神经元损伤相关。作者证实,内毒素注射后,中性粒细胞减少大鼠的SNpc中的神经元丢失较正常大鼠显著减少。此外,完整的SNpc中的星形胶质细胞密度明显低于皮质。而且,内毒素注射后,SNpc的内皮细胞和星形胶质细胞的损害以及血脑屏障的通透性均有显著变化。这些结果都提示,过度的中性粒细胞浸润和环境因子,例如低星形胶质细胞浓度和高血脑屏障通透性,会导致SNpc的重度炎症和神经元死亡。

Regional homogeneity of intrinsic brain activity related to the main alexithymia dimensions

Background Alexithymia is a multidimensional personality construct.Objective This study aims to investigate the neuronal correlates of each alexithymia dimension by examining the regional homogeneity （ReHo） of intrinsic brain activity in a resting situation.Methods From university freshmen, students with alexithymia and non-alexithymia were recruited. Their alexithymic traits were assessed using the Toronto Alexithymia Scale-20. The ReHo was examined using a resting-state functional MRI approach.Results This study suggests signifcant group differences in ReHo in multiple brain regions distributed in the frontal lobe, parietal lobe, temporal lobe, occipital lobe and insular cortex. However, only the ReHo in the insula was positively associated with diffculty identifying feelings, a main dimension of alexithymia. The ReHo in the lingual gyrus, precentral gyrus and postcentral gyrus was？positively associated with diffculty describing feelings in？participants with？alexithymia. Lastly, the ReHo in the right dorsomedial prefrontal cortex （DMPFC_R） was negatively related to the externally oriented thinking style of participants with？alexithymia.Conclusion In conclusion, these results suggest that the main dimensions of alexithymia are correlated with specifc brain regions’ function, and the role of the insula, lingual gyrus, precentral gyrus, postcentral gyrus and DMPFC_R in the neuropathology of alexithymia should be further investigated.

Brain Localization and the Integrated Systems Hypothesis: Evidence from Broca’s Region

The human brain is a fascinatingly complex organ with specialized structures associated with distinct functions. Classical and recent studies on brain localization propose that Broca’s area underpin expressive language and this has been generalized to explain brain functional organization. However, recent neuroimaging studies have shown that the Broca’s area is an extended network that not only participate in its primary function-expressive language processing but in secondary functions-processing non-linguistic/nonverbal tasks as well. Also, there is hierarchical connectivity and interaction of Broca’s region and different brain areas in underlying related primary functions. For this review, I start with revisiting the classical description of brain localization. I then discuss the neuroanatomy of language production and the role of Broca’s region in language processing. I then highlight the participation of the Broca’s area in non-linguistic tasks and non-primary linguistic tasks. Ultimately, I propose a novel hypothesis called integrated systems hypothesis. The integrated systems hypothesis is useful for guiding research on the multimodal role of specific localized integrated systems of the brain especially the role of the Broca’s region in integrating linguistic and non-linguistic processing and how this facilitate language production.

Acupuncture inhibits cue-induced heroin craving and brain activation

Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point （ST36） without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving.

Activated and deactivated functional brain areas in the Deqi state: A functional MRI study

We compared the activities of functional regions of the brain in the Deqi versus non-Deqi state, as reported by physicians and subjects cludng acupuncture, Twelve healthy volunteers received sham and true needling at the Waiguan （TE5） acupoint. Real-time cerebral functional MRI showed that compared with non-sensation after sham needling, true needling activated Brodmann areas 3, 6, 8, 9, 10, 11, 13, 20, 21, 37, 39, 40, 43, and 47, the head of the caudate nucleus, the parahippocampal gyrus, thalamus and red nucleus. True needling also deactivated Brodmann areas 1,2, 3, 4, 5, 6, 7, 9. 10. 18.24.31.40 and 46.

Effect of glutathione on brain nitric oxide levels in an experimental epilepsy mouse model

BACKGROUND： Oxidative stress plays an important role in the pathophysiology of epilepsy. Glutathione, known as one of the compounds of antioxidant defense, has been shown to inhibit convulsions. Nitric oxide has a proconvulsant effect on a pentylenetetrazole-induced animal model. OBJECTIVE： To evaluate the effects of glutathione administration on nitric oxide levels in brain regions of convulsive and kindling pentylenetetrazole-induced seizure models. DESIGN, TIME, AND SETTING： A randomized, controlled, animal experiment. The study was performed at the Department of Physiology, Gaziantep University and Department of Chemistry-Biochemistry,Kahramamaras Sutcu Imam University in 2006. MATERIALS： Pentylenetetrazole and glutathione were purchased from Sigma, USA. METHODS： A total of 80 mice were assigned to 8 groups （n = 10）： normal control, saline control （1 mL normal saline）, convulsive pentylenetetrazole （single intraperitoneal administration of pentylenetetrazole, 60 mg/kg）, convulsive pentylenetrazole plus glutathione （single administration of 60 mg/kg pentylenetetrazole and 200 mg/kg glutathione）, five-dose glutathione （intraperitoneal injection of 200 mg/kg glutathione respectively at 1, 3, 5, 7, and 10 days）, single-dose glutathione （single administration of 200 mg/kg glutathione）, pentylenetetrazole kindling （intraperitoneal administration of pentylenetetrazole of 40 mg/kg at 1,3, 5, 7, and 10 days）, and pentylenetetrazole kindling plus glutathione group （intraperitoneal injection of 40 mg/kg pentylenetetrazole and 200 mg/kg glutathione respectively at 1, 3, 5, 7, and 10 days）. MAIN OUTCOME MEASURES： All mice were sacrificed 1 hour after the last administration. Brain nitric oxide levels were determined by spectrophotometry. RESULTS： There were no significant differences in nitric oxide levels between the normal control, saline control, five-dose glutathione, and single-dose glutathione groups （P 〉 0.05）. Nitric oxide levels in the cerebral hemisphere and cerebellum were significantly less in the convulsive pentylenetetrazole group, compared with the convulsive pentylenetetrazole plus glutathione group （P 〈 0.01）, and levels in the pentylenetetrazole kindling group were remarkably greater than the remaining groups （P 〈 0.01 ）. Brain nitric oxide levels in all groups gradually decreased from the right brain stem to the left brain stem, cerebellum, left cerebral hemisphere, and right cerebral hemisphere. CONCLUSION： Glutathione regulated nitric oxide levels in various brain regions of pentylenetetrazole-induced kindling models, and did not affect nitric oxide levels in the control mice. These results indicated that glutathione played a role when nitric oxide was over-produced. In addition, the brain stem exhibited the highest levels of nitric oxide in both control mice and pentylenetetrazole-induced kindling models.

Differential expression of glial cell line-derived neurotrophic factor splice variants in the mouse brain

Glial cell line-derived neurotrophic factor(GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain,α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neuroprotective effects on dopamine neurons. However, the expression of the GDNF splice variants in dopaminergic neurons in the brain remains unclear. Therefore, in this study, we investigated the mRNA and protein expression of α-and β-pro-GDNF in the mouse brain by real-time quantitative polymerase chain reaction, using splice variant-specific primers, and western blot analysis. At the mRNA level,β-pro-GDNF expression was significantly greater than that of α-pro-GDNF in the mouse brain. In contrast, at the protein level,α-pro-GDNF expression was markedly greater than that of β-pro-GDNF. To clarify the mechanism underlying this inverse relationship in mRNA and protein expression levels of the GDNF splice variants, we analyzed the expression of sorting protein-related receptor with A-type repeats(SorLA) by real-time quantitative polymerase chain reaction. At the mRNA level, SorLA was positively associated with β-pro-GDNF expression, but not with α-pro-GDNF expression. This suggests that the differential expression of α-and β-pro-GDNF in the mouse brain is related to SorLA expression. As a sorting protein, SorLA could contribute to the inverse relationship among the mRNA and protein levels of the GDNF isoforms. This study was approved by the Animal Ethics Committee of Xuzhou Medical University, China on July 14, 2016.

基于Partial New Causality的因果脑网络情绪识别

为了研究情绪产生过程中脑区以及通道之间的因果作用,在部分格兰杰与新型因果关系的基础上,提出一种用于研究时间序列之间因果关系的部分新型因果关系(PNC)方法。在不同情绪下选取脑区内的8个通道,用PNC计算脑区内通道之间的因果连接关系,根据连接关系构建因果网络;对因果网络中节点的信息流向和介数属性进行分析,将PNC因果网络和Granger因果网络节点之间的因果连接视为一种特征送入SVM中训练分类。实验结果表明,基于PNC因果网络和Granger因果网络的平均识别精度分别为76.4%和68.5%,PNC可用于计算时间序列之间的因果关系。

基于深层图卷积的EEG情绪识别方法研究

针对浅层图卷积提取的局部脑区空间关联信息对情感脑电表征不足的问题,本文提出了一种深层图卷积网络模型。该模型利用深层图卷积学习情绪脑电全局通道间的内在关系,在卷积传播过程中应用残差连接和权重自映射解决深层图卷积网络面临的节点特征收敛到固定空间无法学习到有效特征的问题,并在卷积层后加入PN正则化扩大不同情绪特征间的距离,提高情绪识别的性能。在SEED数据集上进行实验,与浅层图卷积网络相比准确率提高了0.7%,标准差下降了3.15。结果表明该模型提取的全局脑区空间关联信息对情绪识别的有效性。

Modified technique for volumetric brain tumor measurements

Quantitative measurements of tumor response rate in three dimensions (3D) become more re-alistic with the use of advanced technology im-aging during therapy, especially when the tumor morphological changes remain subtle, irregular and difficult to assess by clinical examination. These quantitative measurements depend strongly on the accuracy of the segmentations methods used. Improvements on such methods yield to increase the accuracy of the segmentation process. Recently, the essential modification in the Traditional Region Growing (T-RG) method has been developed and a “Modified Region Growing Method” (MRGM) has been presented and gives more accurate boundary detection and holes filling after segmentation. In this pa-per, the new automatic calculation of the volu-metric size of brain tumor has been imple-mented based on Modified Region Growing Method. A comparative study and statistical analysis performed in this work show that the modified method gives more accurate and better performance for 3D volume measurements. The method was tested by 7 fully investigated pa-tients of different tumor type and shape, and better accurate results were reported using MRGM.

带状疱疹后遗神经痛疼痛矩阵的研究进展

带状疱疹后遗神经痛(PHN)是一种典型的慢性神经性疼痛综合征,外周和中枢神经系统作用机制均被认为参与了PHN,但中枢神经系统相关脑网络结构和功能尚未完全阐明,限制了临床镇痛药物及其他干预策略的研究。近年来,疼痛矩阵相关脑网络的研究有助于揭示疼痛的中枢神经系统调节机制,但PHN疼痛矩阵的研究报道较少。现就近年关于PHN疼痛矩阵的研究进行综述,回顾性分析疼痛相关具体脑区的功能及结构变化,旨在为探索高效靶向的镇痛治疗提供新的思路。

Functional magnetic resonance imaging of regional homogeneity changes in parkinsonian resting tremor

Regional homogeneity analysis of low-frequency blood oxygenation level-dependent signals from neighboring voxels enables the analysis of local neuronal synchrony. Both structural magnetic resonance imaging and resting-state functional magnetic resonance imaging scans were collected from nine Parkinson＇s disease patients with right resting tremor, and from eight age-matched normal controls. Regional homogeneity was compared between Parkinson＇s disease patients and controls. The results revealed that regional homogeneity was increased in several brain regions, including the right precuneus, right superior parietal gyrus, left anterior cingulate cortex, right middle frontal gyrus and right inferior frontal gyrus. Conversely, regional homogeneity was decreased in the cerebellar vermis in Parkinson＇s disease patients compared with healthy controls.