Effects of traumatic brain injury on working memory-related brain activation in adolescents.

Eight adolescents (ages 13-18 years) who sustained traumatic brain injury (TBI) and eight gender- and age-matched typically developing (TD) adolescents underwent event-related functional MRI (fMRI) while performing a Sternberg letter recognition task. Encoding, maintenance, and retrieval were examined with memory loads of one or four items during imaging. Both groups performed above a 70% accuracy criterion and did not differ in performance. TD adolescents showed greater increase in frontal and parietal activation during high-load relative to low-load maintenance than the TBI group. The TBI patients showed greater increase in activation during high-load relative to low-load encoding and retrieval than the TD group. Results from this preliminary study suggest that the capability to differentially allocate neural resources according to memory load is disrupted by TBI for the maintenance subcomponent of working memory. The overrecruitment of frontal and extrafrontal regions during encoding and retrieval following TBI may represent a compensatory process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multi‐modal brain tumor image segmentation based on SDAE

Accurate tumor segmentation has the ability to provide doctors with a basis for surgical planning. Moreover, brain tumor segmentation needs to extract different tumor tissues (Edema, tumor, tumor enhancement, and necrosis) from normal tissues which is a big challenge because tumor structures vary considerably across patients in terms of size, extension, and localization. In this article, we evaluate a fully automated method for segmenting brain tumor images from multi‐modal magnetic resonance imaging volumes based on stacked de‐noising auto‐encoders (SDAEs). Specially, we adopted multi‐modality information from T1, T1c, T2, and Flair images, respectively. We extracted gray level patches from different modalities as the input of the SDAE. After trained by the SDAE, the raw network parameters will be obtained, which are adopted as a parameter of the feed forward neural network for classification. A simple post‐processing is implemented by threshold segmentation method to generate a mask to get the final segmentation result. By evaluating the proposed method on the BRATS 2015, it can be proven that our method obtains the better performance than other state‐of‐the‐art counterpart methods. And a preliminary dice score of 0.86 for whole tumor segmentation has been achieved.     

NKG2C+ NK Cells for Immunotherapy of Glioblastoma Multiforme

In glioblastoma, non-classical human leucocyte antigen E (HLA-E) and HLA-G are frequently overexpressed. HLA-E loaded with peptides derived from HLA class I and from HLA-G contributes to inhibition of natural killer (NK) cells with expression of the inhibitory receptor CD94/NKG2A. We investigated whether NK cells expressing the activating CD94/NKG2C receptor counterpart were able to exert anti-glioma effects. NKG2C+ subsets were preferentially expanded by a feeder cell line engineered to express an artificial disulfide-stabilized trimeric HLA-E ligand (HLA-E*spG). NK cells expanded by a feeder cell line, which facilitates outgrowth of conventional NKG2A+, and fresh NK cells, were included for comparison. Expansion via the HLA-E*spG feeder cells selectively increased the fraction of NKG2C+ NK cells, which displayed a higher frequency of KIR2DL2/L3/S2 and CD16 when compared to expanded NKG2A+ NK cells. NKG2C+ NK cells exhibited increased cytotoxicity against K562 and KIR:HLA-matched and -mismatched primary glioblastoma multiforme (GBM) cells when compared to NKG2A+ NK cells and corresponding fresh NK cells. Cytotoxic responses of NKG2C+ NK cells were even more pronounced when utilizing target cells engineered with HLA-E*spG. These findings support the notion that NKG2C+ NK cells have potential therapeutic value for treating gliomas.     

参与中文配对词语联想学习记忆的脑区和神经机制——脑功能磁共振的研究

通过脑功能磁共振技术,研究健康人参与语言的词语配对联想学习记忆任务的脑区和神经机制。对16名右利手健康志愿者进行一项词语配对联想学习记忆任务作业的同时,进行脑功能磁共振扫描。实验采用组块设计,实验任务（包括记忆编码相和记忆提取相）与对照任务（共两个相）交替进行;数据采用SPM99软件进行数据分析和脑功能区定位。结果表明：左侧额叶,特别是左侧额叶的额中下回和枕叶的18,19区在词语联想学习记忆的编码阶段中起重要作用;而左侧顶上小叶、缘上回和角回则在进行记忆提取阶段起重要作用;左侧纹状体边缘区参与了人脑词语联想学习记忆作业的编码阶段。揭示了人大脑完成语言联想学习记忆任务时,除额、顶、枕和颞叶的皮层结构参与外,还新发现有皮层下结构如纹状体参与了词语联想学习记忆。在配对词语的编码和提取阶段,激活的脑区有所变化,显示了这两个语言阶段的神经活动变化机制。     

基于EEG微状态方法的视觉想象识别研究

运动想象M I是基于想象的脑机交互BCI中常用的任务,但M I不易习得和控制,且存在"BCI盲"现象,使得该类BCI的实用化受限.针对较易习得和控制的视觉想象VI任务进行识别,旨在构建基于VI的BCI(VI-BCI).招募了15名被试者参加2种动态图像的视觉想象任务并采集脑电EEG数据;然后采用EEG微状态方法研究了这...     

ILB®, a Low Molecular Weight Dextran Sulphate,Restores Glutamate Homeostasis,Amino Acid Metabolism and Neurocognitive Functions in a Rat Model of Severe Traumatic Brain Injury

In a previous study, we found that administration of ILB^®, a new low molecular weight dextran sulphate, significantly improved mitochondrial functions and energy metabolism, as well as decreased oxidative/nitrosative stress, of brain tissue of rats exposed to severe traumatic brain injury (sTBI), induced by the closed-head weight-drop model of diffused TBI. Using aliquots of deproteinized brain tissue of the same animals of this former study, we here determined the concentrations of 24 amino acids of control rats, untreated sTBI rats (sacrificed at 2 and 7 days post-injury) and sTBI rats receiving a subcutaneous ILB^® administration (at the dose levels of 1, 5 and 15 mg/kg b.w.) 30 min post-impact (sacrificed at 2 and 7 days post-injury). Additionally, in a different set of experiments, new groups of control rats, untreated sTBI rats and ILB^®-treated rats (administered 30 min after sTBI at the dose levels of 1 or 5 mg/kg b.w.) were studied for their neurocognitive functions (anxiety, locomotor capacities, short- and long-term memory) at 7 days after the induction of sTBI. Compared to untreated sTBI animals, ILB^® significantly decreased whole brain glutamate (normalizing the glutamate/glutamine ratio), glycine, serine and γ-aminobutyric acid. Furthermore, ILB^® administration restored arginine metabolism (preventing nitrosative stress), levels of amino acids involved in methylation reactions (methionine, L-cystathionine, S-adenosylhomocysteine), and N-acetylaspartate homeostasis. The macroscopic evidences of the beneficial effects on brain metabolism induced by ILB^® were the relevant improvement in neurocognitive functions of the group of animals treated with ILB^® 5 mg/kg b.w., compared to the marked cognitive decline measured in untreated sTBI animals. These results demonstrate that ILB^® administration 30 min after sTBI prevents glutamate excitotoxicity and normalizes levels of amino acids involved in crucial brain metabolic functions. The ameliorations of amino acid metabolism, mitochondrial functions and energy metabolism in ILB^®-treated rats exposed to sTBI produced significant improvement in neurocognitive functions, reinforcing the concept that ILB^® is a new effective therapeutic tool for the treatment of sTBI, worth being tested in the clinical setting.     

跨模态融合的双注意力脑肿瘤分割算法

针对脑肿瘤多模态信息融合不充分以及肿瘤区域细节信息丢失等问题,提出了一种跨模态融合的双注意力脑肿瘤图像分割网络(CFDA-Net).在编码器-解码器的基础结构上,首先在编码器分支采用密集块与大内核注意力并行的新卷积块,可以使全局和局部信息有效融合且可以防止反向传播时梯度消失的问题;其次在编码器的第2、3和4层的左侧加入多模态深度融合模块,有效地利用不同模态间的互补信息;然后在解码器分支使用Shuffle Attention注意力将特征图分组处理后再聚合,其中分组的子特征一分为二地获取空间与通道的重要注意特征.最后使用二进制交叉熵(binary cross entropy, BCE)、Dice Loss与L2 Loss组成新的混合损失函数,缓解了脑肿瘤数据的类别不平衡问题,进一步提升分割性能.在BraTS2019脑肿瘤数据集上的实验结果表明,该模型在整体肿瘤区域、肿瘤核心区域和肿瘤增强区域的平均Dice系数值分别为0.887、0.892和0.815.与其他先进的分割方法 ADHDC-Net、SDS-MSA-Net等相比,该模型在肿瘤核心区域和增强区域具有更好的分割效果.     

I2-Imidazoline Ligand CR4056 Improves Memory,Increases ApoE Expression and Reduces BBB Leakage in 5xFAD Mice

Recent evidence suggests that I2-imidazoline ligands have neuroprotective properties in animal models of neurodegeneration, such as Alzheimer’s disease (AD). We recently demonstrated that the I2-ligand BU224 reversed memory impairments in AD transgenic mice and this effect was not because of reductions in amyloid-β (Aβ) deposition. In this study, our aim was to determine the therapeutic potential of the powerful analgesic I2-imidazoline ligand CR4056 in the 5xFAD model of AD, since this ligand has been proven to be safely tolerated in humans. Sub-chronic oral administration of CR4056 (30 mg/kg for 10 days) led to an improvement in recognition memory in 6-month-old 5xFAD mice, but not in wild-type littermates, without affecting Aβ levels or deposition. Our results also revealed a change in the profile of microglia by CR4056, resulting in a suppression of pro-inflammatory activated microglia, but increased the density of astrocytes and the expression of ApoE, which is mainly produced by these glial cells. In addition, CR4056 restored fibrinogen extravasation, affecting the distribution of markers of astrocytic end feet in blood vessels. Therefore, these results suggest that CR4056 protects against Aβ-mediated neuroinflammation and vascular damage, and offers therapeutic potential at any stage of AD.     

Melatonin and the Brain–Heart Crosstalk in Neurocritically Ill Patients—From Molecular Action to Clinical Practice

Brain injury, especially traumatic brain injury (TBI), may induce severe dysfunction of extracerebral organs. Cardiac dysfunction associated with TBI is common and well known as the brain–heart crosstalk, which broadly refers to different cardiac disorders such as cardiac arrhythmias, ischemia, hemodynamic insufficiency, and sudden cardiac death, which corresponds to acute disorders of brain function. TBI-related cardiac dysfunction can both worsen the brain damage and increase the risk of death. TBI-related cardiac disorders have been mainly treated symptomatically. However, the analysis of pathomechanisms of TBI-related cardiac dysfunction has highlighted an important role of melatonin in the prevention and treatment of such disorders. Melatonin is a neurohormone released by the pineal gland. It plays a crucial role in the coordination of the circadian rhythm. Additionally, melatonin possesses strong anti-inflammatory, antioxidative, and antiapoptotic properties and can modulate sympathetic and parasympathetic activities. Melatonin has a protective effect not only on the brain, by attenuating its injury, but on extracranial organs, including the heart. The aim of this study was to analyze the molecular activity of melatonin in terms of TBI-related cardiac disorders. Our article describes the benefits resulting from using melatonin as an adjuvant in protection and treatment of brain injury-induced cardiac dysfunction.     

Regulation and Release of Vasoactive Endoglin by Brain Endothelium in Response to Hypoxia/Reoxygenation in Stroke

In large vessel occlusion stroke, recanalization to restore cerebral perfusion is essential but not necessarily sufficient for a favorable outcome. Paradoxically, in some patients, reperfusion carries the risk of increased tissue damage and cerebral hemorrhage. Experimental and clinical data suggest that endothelial cells, representing the interface for detrimental platelet and leukocyte responses, likely play a crucial role in the phenomenon referred to as ischemia/reperfusion (I/R)-injury, but the mechanisms are unknown. We aimed to determine the role of endoglin in cerebral I/R-injury; endoglin is a membrane-bound protein abundantly expressed by endothelial cells that has previously been shown to be involved in the maintenance of vascular homeostasis. We investigated the expression of membranous endoglin (using Western blotting and RT-PCR) and the generation of soluble endoglin (using an enzyme-linked immunosorbent assay of cell culture supernatants) after hypoxia and subsequent reoxygenation in human non-immortalized brain endothelial cells. To validate these in vitro data, we additionally examined endoglin expression in an intraluminal monofilament model of permanent and transient middle cerebral artery occlusion in mice. Subsequently, the effects of recombinant human soluble endoglin were assessed by label-free impedance-based measurement of endothelial monolayer integrity (using the xCELLigence DP system) and immunocytochemistry. Endoglin expression is highly inducible by hypoxia in human brain endothelial monolayers in vitro, and subsequent reoxygenation induced its shedding. These findings were corroborated in mice during MCAO; an upregulation of endoglin was displayed in the infarcted hemispheres under occlusion, whereas endoglin expression was significantly diminished after transient MCAO, which is indicative of shedding. Of note is the finding that soluble endoglin induced an inflammatory phenotype in endothelial monolayers. The treatment of HBMEC with endoglin resulted in a decrease in transendothelial resistance and the downregulation of VE-cadherin. Our data establish a novel mechanism in which hypoxia triggers the initial endothelial upregulation of endoglin and subsequent reoxygenation triggers its release as a vasoactive mediator that, when rinsed into adjacent vascular beds after recanalization, can contribute to cerebral reperfusion injury.