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.

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.

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.

Neural stem cell-derived exosomes promote mitochondrial biogenesis and restore abnormal protein distribution in a mouse model of Alzheimer's disease

Mitochondrial dysfunction is a hallmark of Alzheimer’s disease.We previously showed that neural stem cell-derived extracellular vesicles improved mitochondrial function in the cortex of AP P/PS1 mice.Because Alzheimer’s disease affects the entire brain,further research is needed to elucidate alterations in mitochondrial metabolism in the brain as a whole.Here,we investigated the expression of several important mitochondrial biogenesis-related cytokines in multiple brain regions after treatment with neural stem cell-derived exosomes and used a combination of whole brain clearing,immunostaining,and lightsheet imaging to clarify their spatial distribution.Additionally,to clarify whether the sirtuin 1(SIRT1)-related pathway plays a regulatory role in neural stem cell-de rived exosomes interfering with mitochondrial functional changes,we generated a novel nervous system-SIRT1 conditional knoc kout AP P/PS1mouse model.Our findings demonstrate that neural stem cell-de rived exosomes significantly increase SIRT1 levels,enhance the production of mitochondrial biogenesis-related fa ctors,and inhibit astrocyte activation,but do not suppress amyloid-βproduction.Thus,neural stem cell-derived exosomes may be a useful therapeutic strategy for Alzheimer’s disease that activates the SIRT1-PGC1αsignaling pathway and increases NRF1 and COXIV synthesis to improve mitochondrial biogenesis.In addition,we showed that the spatial distribution of mitochondrial biogenesis-related factors is disrupted in Alzheimer’s disease,and that neural stem cell-derived exosome treatment can reverse this effect,indicating that neural stem cell-derived exosomes promote mitochondrial biogenesis.

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.

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.

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-alexlthymia 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 significant gro叩 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 difficulty identifying feelings, a main dimension of alexithymia. The ReHo in the lingual gyrus,precentral gyrus and postcentral gyrus was positively associated with difficulty 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 specific 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.

Increased activation of the caudate nucleus and parahippocampal gyrus in Parkinson's disease patients with dysphagia after repetitive transcranial magnetic stimulation:a case-control study

Repetitive transcranial magnetic stimulation(r TMS)has been shown to effectively improve impaired swallowing in Parkinson's disease(PD)patients with dysphagia.However,little is known about how r TMS affects the corresponding brain regions in this patient group.In this casecontrol study,we examined data from 38 PD patients with dysphagia who received treatment at Beijing Rehabilitation Medicine Academy,Capital Medical University.The patients received high-frequency r TMS of the motor cortex once per day for 10 successive days.Changes in brain activation were compared via functional magnetic resonance imaging in PD patients with dysphagia and healthy controls.The results revealed that before treatment,PD patients with dysphagia showed greater activation in the precentral gyrus,supplementary motor area,and cerebellum compared with healthy controls,and this enhanced activation was weakened after treatment.Furthermore,before treatment,PD patients with dysphagia exhibited decreased activation in the parahippocampal gyrus,caudate nucleus,and left thalamus compared with healthy controls,and this activation increased after treatment.In addition,PD patients with dysphagia reported improved subjective swallowing sensations after r TMS.These findings suggest that swallowing function in PD patients with dysphagia improved after r TMS of the motor cortex.This may have been due to enhanced activation of the caudate nucleus and parahippocampal gyrus.The study protocol was approved by the Ethics Committee of Beijing Rehabilitation Hospital of Capital Medical University(approval No.2018 bkky017)on March 6,2018 and was registered with Chinese Clinical Trial Registry(registration No.Chi CTR 1800017207)on July 18,2018.

Different types of drug abusers prefrontal cortex activation patterns and based on machine-learning classification

Drug addiction can cause abnormal brain activation changes,which are the root cause of drug craving and brain function errors.This study enrolled drug abusers to determine the effects of different drugs on brain activation.A functional near-infrared spectroscopy(fNIRS)device was used for the research.This study was designed with an experimental paradigm that included the induction of resting and drug addiction cravings.We collected the fNIRS data of 30 drug users,including 10 who used heroin,10 who used Methamphetamine,and 10 who used mixed drugs.First,using Statistical Analysis,the study analyzed the activations of eight functional areas of the left and right hemispheres of the prefrontal cortex of drug addicts who respectively used heroin,Methamphetamine,and mixed drugs,including Left/Right-Dorsolateral prefrontal cortex(L/R-DLPFC),Left/Right-Ventrolateral prefrontal cortex(L/R-VLPFC),Left/Right-Fronto-polar prefrontal cortex(L/R-FPC),and Left/Right Orbitofrontal Cortex(L/R-OFC).Second,referencing the degrees of activation of oxyhaemoglobin concentration(HbO2),the study made an analysis and got the specific activation patterns of each group of the addicts.Finally,after taking out data which are related to the addicts who recorded high degrees of activation among the three groups of addicts,and which had the same channel numbers,the paper classified the different drug abusers using the data as the input data for Convolutional Neural Networks(CNNs).The average three-class accuracy is 67.13%.It is of great significance for the analysis of brain function errors and personalized rehabilitation.

Evidence of cortical reorganization of language networks after stroke with subacute Broca's aphasia:a blood oxygenation level dependent-functional magnetic resonance imaging study

Aphasia is an acquired language disorder that is a common consequence of stroke.The pathogenesis of the disease is not fully understood,and as a result,current treatment options are not satisfactory.Here,we used blood oxygenation level-dependent functional magnetic resonance imaging to evaluate the activation of bilateral cortices in patients with Broca＇s aphasia 1 to 3 months after stroke.Our results showed that language expression was associated with multiple brain regions in which the right hemisphere participated in the generation of language.The activation areas in the left hemisphere of aphasia patients were significantly smaller compared with those in healthy adults.The activation frequency,volumes,and intensity in the regions related to language,such as the left inferior frontal gyrus（Broca＇s area）,the left superior temporal gyrus,and the right inferior frontal gyrus（the mirror region of Broca＇s area）,were lower in patients compared with healthy adults.In contrast,activation in the right superior temporal gyrus,the bilateral superior parietal lobule,and the left inferior temporal gyrus was stronger in patients compared with healthy controls.These results suggest that the right inferior frontal gyrus plays a role in the recovery of language function in the subacute stage of stroke-related aphasia by increasing the engagement of related brain areas.

Anovel multi-dimensional features fusion algorithm for the EEG signal recognition of brain’s sensorimotor region activated tasks

Purpose-Aiming at the shortcomings of EEG signals generated by brain’s sensorimotor region activated tasks,such as poor performance,low efficiency and weak robustness,this paper proposes an EEG signals classification method based on multi-dimensional fusion features.Design/methodology/approach-First,the improved Morlet wavelet is used to extract the spectrum feature maps from EEG signals.Then,the spatial-frequency features are extracted from the PSD maps by using the three-dimensional convolutional neural networks(3DCNNs)model.Finally,the spatial-frequency features are incorporated to the bidirectional gated recurrent units(Bi-GRUs)models to extract the spatial-frequencysequential multi-dimensional fusion features for recognition of brain’s sensorimotor region activated task.Findings-In the comparative experiments,the data sets of motor imagery(MI)/action observation(AO)/action execution(AE)tasks are selected to test the classification performance and robustness of the proposed algorithm.In addition,the impact of extracted features on the sensorimotor region and the impact on the classification processing are also analyzed by visualization during experiments.Originality/value-The experimental results show that the proposed algorithm extracts the corresponding brain activation features for different action related tasks,so as to achieve more stable classification performance in dealing with AO/MI/AE tasks,and has the best robustness on EEGsignals of different subjects.

Effects of methylphenidate on resting-state brain activity in normal adults: an fMRI study

Methylphenidate （MPH） is one of the most commonly used stimulants for the treatment of attention deficit hyperactivity disorder （ADHD）. Although several studies have evaluated the effects of MPH on human brain activation during specific cognitive tasks using functional magnetic resonance imaging （fMRI）, few studies have focused on spontaneous brain activity. In the current study, we investigated the effect of MPH on the intra-regional synchronization of spontaneous brain activity during the resting state in 18 normal adult males. A handedness questionnaire and the Wechsler Adult Intelligence Scale were applied before medication, and a resting-state fMRI scan was obtained 1 h after medication （20 mg MPH or placebo, order counterbalanced between participants）. We demonstrated that： （1） there were no significant differences in the performance of behavioral tasks between the MPH and placebo groups; （2） the left middle and superior temporal gyri had stronger MPH-related regional homogeneity （ReHo）; and （3） the left lingual gyrus had weaker MPH-related ReHo. Our findings showed that the ReHo in some brain areas changes with MPH compared to placebo in normal adults, even though there are no behavioral differences. This method can be applied to patients with mental illness who may be treated with MPH, and be used to compare the difference between patients taking MPH and normal participants, to help reveal the mechanism of how MPH works.

Deep learning-based large-scale named entity recognition for anatomical region of mammalian brain

Background:Images of anatomical regions and neuron type distribution,as well as their related literature are valuable assets for neuroscience research.They are vital evidence and vehicles in discovering new phenomena and knowledge refinement through image and text big data.The knowledge acquired from image data generally echoes with the literature accumulated over the years.The knowledge within the literature can provide a comprehensive context for a deeper understanding of the image data.However,it is quite a challenge to manually identify the related literature and summarize the neuroscience knowledge in the large-scale corpus.Thus,neuroscientists are in dire need of an automated method to extract neuroscience knowledge from large-scale literature.Methods:A proposed deep learning model named BioBERT-CRF extracts brain region entities from the WhiteText dataset.This model takes advantage of BioBERT and CRF to predict entity labels while training.Results:The proposed deep learning model demonstrated comparable performance against or even outperforms the previous models on the WhiteText dataset.The BioBERT-CRF model has achieved the best average precision,recall,and F1 score of 81.3%,84.0%,and 82.6%,respectively.We used the BioBERT-CRF model to predict brain region entities in a large-scale PubMed abstract dataset and used a rule-based method to normalize all brain region entities to three neuroscience dictionaries.Conclusions:Our work shows that the BioBERT-CRF model can be well-suited for brain region entity extraction.The rankings of different brain region entities by their appearance in the large-scale corpus indicate the anatomical regions that researchers are most concerned about.