发展性阅读障碍的脑机制——来自脑成像研究的证据

发展性阅读障碍是一种特殊的学习障碍,发展性阅读障碍的脑机制一直是研究者们关心的一个重要问题．随着脑成像技术的应用,人们在发展性阅读障碍的脑机制研究方面取得了重大进展．脑结构研究发现,发展性阅读障碍者在颞-顶叶、颞-枕叶、额下回、小脑等区域都存在一定的脑结构异常,这些脑结构异常要么表现在某个脑区的结构上,要么表现某个脑区结构的左右不对称性上．脑功能研究发现,发展性阅读障碍者出现脑结构异常的区域也大多表现出脑功能的异常．脑功能连接的研究发现,发展性阅读障碍者脑功能连接的异常不仅涉及到同侧脑区前后部分的连接,还涉及双侧脑区相应部分的连接．另外,中文发展性阅读障碍的研究发现了与拼音文字发展性阅读障碍不同的脑机制．这些研究成果为进一步揭示发展性阅读障碍的脑机制以及拓展中文发展性阅读障碍的研究提供了借鉴．     

Administration of Myo-inositol Plus Ethanolamine Elevates Phosphatidylethanolamine Plasmalogen in the Rat Cerebellum

Plasmalogens are ether-linked phospholipids highly abundant in nervous tissue. Previously we demonstrated that acute administration of myo-inositol (myo-Ins) + [2-¹³C] ethanolamine ([2-¹³C]Etn) significantly elevated phosphatidylethanolamine plasmalogen (PlsEtn) in rat whole brain. Current experiments investigated the effects of acute myo-Ins+[2-¹³C]Etn administration on [PlsEtn] and the biosynthesis of new Etn lipids using NMR spectroscopy in rat cerebral cortex, hippocampus, brainstem, midbrain and cerebellum. Treated rats received a single dose of myo-Ins+[2-¹³C]Etn and controls received saline rather than myo-Ins. Data reveal that the cerebellum is the brain region most affected by treatment, which resulted in a 22% increase in [PlsEtn] and 89% increase in newly synthesized Etn lipids relative to controls (P 0.05). Furthermore, the cerebellar PlsEtn/phosphatidylethanolamine ratio and molar percentage of PlsEtn were significantly elevated by 12% and 8%, respectively (P 0.05). These data suggest that myo-Ins influences Etn lipid metabolism in brain, particularly in the cerebellum where there is a stimulation in the biosynthesis of new Etn lipids with a preference towards PlsEtn.     

编者按: 脑与认知科学研究的现状与前沿

研究和揭示大脑在生理和病理状态下的工作机制,一直是脑与认知科学的重要研究内容和目标.虽然脑与认知科学领域已经取得了一系列重要的研究成果,但仍然面临巨大的挑战.因此,各国都在加大投入,推动技术创新,开展多学科交叉、多层次的脑与认知科学研究.2013年美国启动脑科学     

脑机接口：现状，问题与展望

本文综述现有脑机接口技术的最新发展，并讨论这些脑机接口技术的局限和存在的问题，如高估人类个体大脑的功能、对大脑信息存储方式缺乏了解等. 基于大脑信息存储的“二维码”模型，我们认为目前的脑机接口技术方案仅适用于一些简单的应用场景，如了解受测者的情绪变化、生命活动的状态，以及控制体外器械等，而无法通过脑机接口技术获取脑内诸如记忆与思考等信息的精准细节. 我们也提出，向大脑输入信息的脑机接口技术有较大的发展空间，比如发展具有多种调控效果、物理和生化技术结合的深脑刺激装置，有可能广泛应用于抑郁症、癫痫等脑疾病的治疗，以及应用于短期脑力的增强. 本文对于目前的脑机接口研究领域具有一定的警示和启发意义.     

花粉制剂对脑衰老动物各脑区的SOD和NO水平的影响

采用 D-半乳糖建立脑衰老动物模型 ,观察服用花粉制剂前后对脑衰老模型动物不同脑区组织中超氧化物歧化酶 ( SOD)活性、一氧化氮 ( NO)水平的影响。结果表明花粉制剂能明显升高脑衰老动物某些脑区 SOD活性和降低脑衰老动物某些脑区 NO水平。研究结果提示花粉制剂具有延缓衰老和增强记忆力等作用 ,其机制可能与其促进自由基的清除及减少 NO释放有关。     

Trophic factors and cell therapy to stimulate brain repair after ischaemic stroke

Brain repair involves a compendium of natural mechanisms that are activated following stroke. From a therapeutic viewpoint, reparative therapies that encourage cerebral plasticity are needed. In the last years, it has been demonstrated that modulatory treatments for brain repair such as trophic factor- and stem cell-based therapies can promote neurogenesis, gliogenesis, oligodendrogenesis, synaptogenesis and angiogenesis, all of which having a beneficial impact on infarct volume, cell death and, finally, and most importantly, on the functional recovery. However, even when promising results have been obtained in a wide range of experimental animal models and conditions these preliminary results have not yet demonstrated their clinical efficacy. Here, we focus on brain repair modulatory treatments for ischaemic stroke, that use trophic factors, drugs with trophic effects and stem cell therapy. Important and still unanswered questions for translational research ranging from experimental animal models to recent and ongoing clinical trials are reviewed here.     

Alteration of Protease Levels in Different Brain Areas of Suicide Victims

Numerous recent studies found that proteases play a major role in brain function. In addition to their role in protein turnover, they have modulatory functions and an important role in apoptosis, pathological changes, and other mechanisms. To explore possible differences in brain protein metabolism of suicide victims, we examined the activity of two proteases, cathepsin D and calpain (I and II combined), in eleven discrete areas of postmortem brain tissue of 21 victims of suicide and of 31 age- and sex-matched control subjects without a history of psychiatric or neurological disease. The levels of functionally important amino acids in five of these areas were also measured. Cathepsin D activity was found to be lower in two of eleven regions of brains of suicide victims, the parahippocampal cortex and the medial hypothalamus, by 26% and 27%, respectively. Calpain activity was lower in two different areas tested, 29% in the medulla oblongata and 26% in the lateral prefrontal cortex, and was 18% higher in the midbrain. There were no significant differences in the other areas (globus pallidus, hippocampus, amygdala, caudate nucleus, ventral tegmental area, and nucleus accumbens). Protease distribution was regionally heterogeneous—the levels in the globus pallidus were low, and in the hippocampus high, with about a two-fold difference. The length of the postmortem period for obtaining tissue, the storage time of the frozen tissue, and the age of the subject had no apparent influence on the results obtained. Although there was a tendency toward higher levels of aspartate and glycine in brain areas from suicide victims, the difference was not significant. The variations among individual brains were greater in amino acid levels than in protease levels. The findings indicate the possible role of protein metabolism in depressive or suicidal behavior.     

Problems of ontogeny and phylogeny in brain-size evolution

Fundamental ambiguities in the interpretation of brain/body allometric trends can only be resolved by analyzing relationships between ontogenetic brain/body growth processes in different groups. The ambiguous concept of adult encephalization confuses at least three distinct types of transformation of a common mammalian growth curve: scalar magnification, total curve didplacement, and changes in proportions of the pre- and postnatal phases of the curve. The conservative ratio between pre- and postnatal growth phases determines the apparent linearity of comparative brain/body allometry and can be explained by assuming that embyological neurogenetic processes ultimately determine both target brain and body size—the first directly and the second indirectly via neurohormonal regulation of somatic growth. Uneven taxonomic distribution of different ontogenetic growth patterns may explain many differences in the allometric trends at different taxonomic levels of analysis. The human brain grows exactly as if it was in a giant ape body; however, because of decoupled growth in different brain regions, it regulates body growth as though it were the size of a chimpanzee brain. Human encephalization exhibits an ontogenetic transformation not found in other mammalian groups.     

Astrocytes in injury states rapidly produce anti-inflammatory factors and attenuate microglial inflammatory responses

Microglia are known to be a primary inflammatory cell type in the brain. However, microglial inflammatory responses are attenuated in the injured brain compared to those in cultured pure microglia. In the present study, we found that astrocytes challenged by oxygen-glucose deprivation (OGD) or H(2) O(2) released soluble factor(s) and attenuated microglial inflammatory responses. Conditioned medium prepared from astrocytes treated with OGD (OGD-ACM) or H(2) O(2) (H(2) O(2) -ACM) significantly reduced the levels of interferon-γ (IFN-γ)-induced microglial inflammatory mediators, including inducible nitric oxide synthase, at both the mRNA and protein levels. The anti-inflammatory effect of astrocytes appeared very rapidly (within 5min), but was not closely correlated with the extent of astrocyte damage. Both OGD-ACM and H(2) O(2) -ACM inhibited STAT nuclear signaling, as evidenced by a reduction in both STAT-1/3 binding to the IFN-γ-activated site and IFN-γ-activated site promoter activity. However, both phosphorylation and nuclear translocation of STAT-1/3 was unchanged in IFN-γ-treated microglia. The active component(s) in OGD-ACM were smaller than 3kDa, and displayed anti-inflammatory effects independent of protein synthesis. These results suggest that, in the injured brain, astrocytes may act as a controller to rapidly suppress microglial activation.     

Evolution of brain region volumes during artificial selection for relative brain size

The vertebrate brain shows an extremely conserved layout across taxa. Still, the relative sizes of separate brain regions vary markedly between species. One interesting pattern is that larger brains seem associated with increased relative sizes only of certain brain regions, for instance telencephalon and cerebellum. Till now, the evolutionary association between separate brain regions and overall brain size is based on comparative evidence and remains experimentally untested. Here, we test the evolutionary response of brain regions to directional selection on brain size in guppies (Poecilia reticulata) selected for large and small relative brain size. In these animals, artificial selection led to a fast response in relative brain size, while body size remained unchanged. We use microcomputer tomography to investigate how the volumes of 11 main brain regions respond to selection for larger versus smaller brains. We found no differences in relative brain region volumes between large‐ and small‐brained animals and only minor sex‐specific variation. Also, selection did not change allometric scaling between brain and brain region sizes. Our results suggest that brain regions respond similarly to strong directional selection on relative brain size, which indicates that brain anatomy variation in contemporary species most likely stem from direct selection on key regions.     

On the mechanism of cerebral accumulation of cholestanol in patients with cerebrotendinous xanthomatosis

The most serious consequence of sterol 27-hydroxylase deficiency in humans [cerebrotendinous xanthomatosis (CTX)] is the development of cholestanol-containing brain xanthomas. The cholestanol in the brain may be derived from the circulation or from 7alpha-hydroxylated intermediates in bile acid synthesis, present at 50- to 250-fold increased levels in plasma. Here, we demonstrate a transfer of 7alpha-hydroxy-4-cholesten-3-one across cultured porcine brain endothelial cells (a model for the blood-brain barrier) that is approximately 100-fold more efficient than the transfer of cholestanol. Furthermore, there was an efficient conversion of 7alpha-hydroxy-4-cholesten-3-one to cholestanol in cultured neuronal and glial cells as well as in monocyte-derived macrophages of human origin. It is concluded that the continuous intracellular production of cholestanol from a bile acid precursor capable of rapidly passing biomembranes, including the blood-brain barrier, is likely to be of major importance for the accumulation of cholestanol in patients with CTX. Such a mechanism also fits well with the observation that treatment with chenodeoxycholic acid, which normalizes the level of the bile acid precursor, results in a reduction of cholestanol-containing xanthomas even in the brain.     

血红素氧合酶-1在脑损伤过程中的作用的研究进展

来源于出血后血红蛋白或衰老细胞释放的血红素能够诱导血红素氧合酶-1（HO-1,HSP-1）的表达。血红素氧合酶-1催化血红素生成气体介质一氧化碳,铁和胆绿素。胆绿素和它的代谢产物胆红素都是有效的抗氧化剂;同时铁诱导的铁蛋白和CO也发挥着各自的保护作用。因此,HO-1的表达被看作一种重要的保护机制。在各种不同的脑病理改变发生后,如蛛网膜下腔出血,脑梗死,创伤性脑损伤及神经变性疾病,HO-1明显表达于小胶质细胞,星形细胞和神经元细胞,从而发挥其重要脑保护作用。     

牛磺酸对脑创伤大鼠的脑保护作用

目的:探讨牛磺酸(Tau)预处理对弥漫性脑创伤(TBI)大鼠脑皮层超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量、脑含水量(BWC)和脑皮层水孔通道蛋白4(AQP4)表达的影响。方法:复制大鼠TBI模型,分为假手术组(S组)、TBI组(T组)、低剂量Tau组(L组)和高剂量Tau组(H组),用比色法测定脑皮层匀浆液中SOD活力和MDA含量;干/湿法测定BWC;免疫组织化学检测脑皮层AQP4的表达。结果:T组大鼠脑皮层SOD活力显著低于S组,T组MDA含量、BWC和脑皮层AQP4的表达显著高于S组;H、L组脑皮层SOD活力显著高于T组,H、L组MDA含量、BWC和脑皮层AQP4的表达显著低于T组;H、L组之间差异无显著性。结论:Tau可能通过清除TBI后产生的的氧自由基、下调TBI大鼠脑皮层AQP4的表达减轻脑水肿,发挥其脑保护作用。     

Cerebral cartography and connectomics

Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics.     

Somatostatin Binding Sites in Human and Monkey Brain: Localization and Characterization

A radioiodinated analogue of somatostatin 28, 125I [Leu8,D-Trp22,Tyr25] SS-28, was used to localize and characterize somatostatin binding sites in both human and monkey brain. High-affinity binding sites (approximately 1 nM) were found in cerebral cortex. The highest binding was in cerebral cortex with intermediate binding found in hippocampus, striatum, and amygdala and low binding in hypothalamus and brainstem. There was a rough correlation between somatostatin receptor binding and concentrations of somatostatin-like immunoreactivity (SLI) in human brain. Somatostatin receptors were stable for up to 24 h in an animal model simulating human autopsy conditions and there was no correlation between postmortem interval and receptor binding in human brain. Pharmacologic characterization in human cortex showed that there was a correlation between the inhibition of receptor binding by somatostatin analogues and their known abilities to inhibit growth hormone secretion. These findings demonstrate that a highly specific membrane-associated receptor for somatostatin is present in both monkey and human brain. Examination of somatostatin receptor binding in Alzheimer's disease and Huntington's disease may improve understanding of the role of somatostatin in both these illnesses.     

血红素氧合酶-1 在脑损伤过程中的作用的研究进展

来源于出血后血红蛋白或衰老细胞释放的血红素能够诱导血红素氧合酶-1(HO-1,HSP-1)的表达。血红素氧合酶-1催化血红素生成气体介质一氧化碳,铁和胆绿素。胆绿素和它的代谢产物胆红素都是有效的抗氧化剂;同时铁诱导的铁蛋白和CO也发挥着各自的保护作用。因此,HO-1的表达被看作一种重要的保护机制。在各种不同的脑病理改变发生后,如蛛网膜下腔出血,脑梗死,创伤性脑损伤及神经变性疾病,HO-1明显表达于小胶质细胞,星形细胞和神经元细胞,从而发挥其重要脑保护作用。     

Influence of acclimation and determination temperature on the oxygen consumption of the brain in two species of anurans

1. 1. The effects of sudden changes by increasing or decreasing the measurement temperature on the oxygen consumption of the brains of Bufo arenarum and Leptodactylus ocellatus were determined.

2. 2. The experiments were carried at in vitro at temperatures which range from 4 to 37°C. The brain was oxygenated and stabilized for 20 min at each of the temperatures to which it was subjected before oxygen consumption measurements were made.

3. 3. A theoretical curve representing the variation of oxygen consumption with temperature was calculated according to the following exponential relationship; for Leptodactylus ocellatus y = 0.408 × 1.07^x and for Bufo arenarum y = 0.389 × 1.065^x.

4. 4. These results were compared with the brain oxygen consumption of animals acclimated to different temperatures, whose oxygen consumption was measured at a fixed temperature. Only Leptodactylus ocellatus had a significantly lower oxygen consumption in a high range of temperatures, indicating thermal compensation, probably to save metabolic reserves.

5. 5. No deterioration of the brain tissue was observed, as several passages from high to low temperatures in the range of 20°–30°C, showed a reversible oxygen consumption in acclimated and non-acclimated Bufo arenarum and Leptodactylus ocellatus.

What can dolphins tell us about primate evolution?

Fifty-five million years ago, a furry, hoofed mammal about the size of a dog ventured into the shallow brackish remnant of the Tethys Sea and set its descendants on a path that would lead to their complete abandonment of the land. These early ancestors of cetaceans (dolphins, porpoises, and whales) thereafter set on an evolutionary course that is arguably the most unusual of any mammal that ever lived. Primates and cetaceans, because of their adaptation to exclusively different physical environments, have had essentially nothing to do with each other throughout their evolution as distinct orders. In fact, the closest phylogenetic relatives of cetaceans are even-toed ungulates.     

Application of PIXE analysis to the study of the regional distribution of trace elements in normal human brain

A particle-induced X-ray emission (PIXE) analysis method is presented, which allows measurement of eight elements (i.e., K, Ca, Mn, Fe, Cu, Zn, Se, and Rb) in human brain samples of only a few mg dry weight. The precision and accuracy of the method were investigated by analyzing animal brain matter with both PIXE and instrumental neutron activation analysis (INAA). The method was applied to measure the 8 elements in 46 different regions of 3 human brains. The sections analyzed originated from either the left or the right cerebral hemisphere, brain stem, and cerebellum. For one of the brains, sections were also analyzed from 26 corresponding regions of both hemispheres. For all elements, similar concentrations were found in the corresponding areas of the left and right sides of the brain. The concentrations (in μg/g dry weight) of the elements K, Fe, Cu, Zn, Se, and Rb were consistently higher in cortical structures than in white matter. Deep nuclei and brain stem, which have a mixed composition, showed intermediate values for K, Zn, Se, and Rb. A hierarchical cluster analysis indicated that the various brain regions clustered into two large groups, one comprising gray and mixed matter regions and the other, white and mixed matter brain areas.