Expression of Nogo-A mRNA after injury of the rat central nervous system

BACKGROUND： Nogo protein has been identified as an inhibitor of axonal growth, which was highly expressed in central nervous system; however, there are only a few studies on changes of Nogo-A expression following central nervous system injury. OBJECTIVE： To investigate the dynamic expression of Nogo-A mRNA after rat central nervous system injury. DESIGN： Randomized controlled animal study. MATERIALS： Thirty-five rats were randomly divided into two groups, normal animal group （n = 5） and model group （n = 30）. The model group was then divided into six subgroups at six time points： 12, 24 hours and 3, 9, 15, and 21 days post-injury, with five rats in each subgroup. METHODS： The left parietal lobe of rats was contused by free-fall strike, and total RNA was extracted from the entire brain tissue. Semi-quantitative RT-PCR was used to detect Nogo-A mRNA expression, and the ratio between expression of the target gene and glyceraldehyde phosphate dehydrogenase was used to determine the relative expression level. MAIN OUTCOME MEASURES： To determine whether Nogo-A mRNA expression was higher than usual following brain injury. RESULTS： The level of Nogo-A mRNA started to increase 12 hours after injury （P 〈 0.05） and decreased slightly by 24 hours post-injury. Expression increased again on day 3 and reached a peak on day 9. Nogo-A mRNA expression started to decrease on day 15, and then decreased to normal levels at days 21 （P 〉 0.05）. CONCLUSION： After injury of the central nervous system, Nogo-A may play a pivotal role in obstructing regeneration of the nerve.

Role of nuclear factor kappa B in central nervous system regeneration

Activation of nuclear factor kappa B （NF-κB） is a hallmark of various central nervous system （CNS） pathologies. Neuron-specific inhibition of its transcriptional activator subunit RelA, also referred to as p65, promotes neuronal survival under a range of conditions, i.e., for ischemic or excitotoxic insults. In macro- and microglial cells, post-lesional activation of NF-κB triggers a growth-permissive program which contributes to neural tissue inflammation, scar formation, and the expression of axonal growth inhibitors. Intriguingly, inhibition of such inducible NF-~B in the neuro-glial compartment, i.e., by genetic ablation of RelA or overexpression of a trans- dominant negative mutant of its upstream regulator IκBa, significantly enhances functional recovery and promotes axonal regeneration in the mature CNS. By contrast, depletion of the NF-κB subunit p50, which lacks transcriptional activator function and acts as a transcriptional repressor on its own, causes precocious neuronal loss and exacerbates axonal degeneration in the lesioned brain. Collectively, the data imply that NF-κB orchestrates a multicellular pro- gram in which κB-dependent gene expression establishes a growth-repulsive terrain within the post-lesioned brain that limits structural regeneration of neuronal circuits. Considering these subunit-specific functions, interference with the NF-κB pathway might hold clinical potentials to improve functional restoration following traumatic CNS injury.

MicroRNAs of microglia： wrestling with central nervous system disease

Microglia serve as brain-resident myeloid cells that affect cerebral development, ischemia, neurodegeneration, and neuro-viral infection. MicroRNAs play a key role in central nervous system disease through post-transcriptional regulation. Indeed, evidence shows that microRNAs are one of the most important regulators mediating microglial activation, polarization, and autophagy, and subsequently affecting neuroinflammation and the outcome of central nervous system disease. In this review, we provide insight into the function of microRNAs, which may be an attractive strategy and influential treatment for microglia-related central nervous system dysfunction. Moreover, we comprehensively describe how microglia fight against central nervous system disease via multiple functional microRNAs.

Modelling the impact of climate change on rangeland forage production using a generalized regression neural network:a case study in Isfahan Province,Central Iran

Monitoring of rangeland forage production at specified spatial and temporal scales is necessary for grazing management and also for implementation of rehabilitation projects in rangelands. This study focused on the capability of a generalized regression neural network（GRNN） model combined with GIS techniques to explore the impact of climate change on rangeland forage production. Specifically, a dataset of 115 monitored records of forage production were collected from 16 rangeland sites during the period 1998–2007 in Isfahan Province, Central Iran. Neural network models were designed using the monitored forage production values and available environmental data（including climate and topography data）, and the performance of each network model was assessed using the mean estimation error（MEE）, model efficiency factor（MEF）, and correlation coefficient（r）. The best neural network model was then selected and further applied to predict the forage production of rangelands in the future（in 2030 and 2080） under A1 B climate change scenario using Hadley Centre coupled model. The present and future forage production maps were also produced. Rangeland forage production exhibited strong correlations with environmental factors, such as slope, elevation, aspect and annual temperature. The present forage production in the study area varied from 25.6 to 574.1 kg/hm^2. Under climate change scenario, the annual temperature was predicted to increase and the annual precipitation was predicted to decrease. The prediction maps of forage production in the future indicated that the area with low level of forage production（0–100 kg/hm^2） will increase while the areas with moderate, moderately high and high levels of forage production（≥100 kg/hm^2） will decrease both in 2030 and in 2080, which may be attributable to the increasing annual temperature and decreasing annual precipitation. It was predicted that forage production of rangelands will decrease in the next couple of decades, especially in the western and southern parts of Isfahan Province. These changes are more pronounced in elevations between 2200 and 2900 m. Therefore, rangeland managers have to cope with these changes by holistic management approaches through mitigation and human adaptations.

The role of the Rho/ROCK signaling pathway in inhibiting axonal regeneration in the central nervous system

The Rho/Rho-associated coiled-coil containing protein kinase（Rho/ROCK） pathway is a major signaling pathway in the central nervous system, transducing inhibitory signals to block regeneration. After central nervous system damage, the main cause of impaired regeneration is the presence of factors that strongly inhibit regeneration in the surrounding microenvironment. These factors signal through the Rho/ROCK signaling pathway to inhibit regeneration. Therefore, a thorough understanding of the Rho/ROCK signaling pathway is crucial for advancing studies on regeneration and repair of the injured central nervous system.

Taking central nervous system regenerative therapies to the clinic: curing rodents versus nonhuman primates versus humans

The central nervous system is known to have limited regenerative capacity.Not only does this halt the human body’s reparative processes after central nervous system lesions,but it also impedes the establishment of effective and safe therapeutic options for such patients.Despite the high prevalence of stroke and spinal cord injury in the general population,these conditions remain incurable and place a heavy burden on patients’families and on society more broadly.Neuroregeneration and neural engineering are diverse biomedical fields that attempt reparative treatments,utilizing stem cells-based strategies,biologically active molecules,nanotechnology,exosomes and highly tunable biodegradable systems(e.g.,certain hydrogels).Although there are studies demonstrating promising preclinical results,safe clinical translation has not yet been accomplished.A key gap in clinical translation is the absence of an ideal animal or ex vivo model that can perfectly simulate the human microenvironment,and also correspond to all the complex pathophysiological and neuroanatomical factors that affect functional outcomes in humans after central nervous system injury.Such an ideal model does not currently exist,but it seems that the nonhuman primate model is uniquely qualified for this role,given its close resemblance to humans.This review considers some regenerative therapies for central nervous system repair that hold promise for future clinical translation.In addition,it attempts to uncover some of the main reasons why clinical translation might fail without the implementation of nonhuman primate models in the research pipeline.

Mild hypothermia as a treatment for central nervous system injuries Positive or negative effects?

Besides local neuronal damage caused by the primary insult, central nervous system injuries may secondarily cause a progressive cascade of related events including brain edema, ischemia, oxida- tive stress, excitotoxicity, and dysregulation of calcium homeostasis. Hypothermia is a beneficial strategy in a variety of acute central nervous system injuries. Mild hypothermia can treat high in- tracranial pressure following traumatic brain injuries in adults. It is a new treatment that increases survival and quality of life for patients suffering from ischemic insults such as cardiac arrest, stroke, and neurogenic fever following brain trauma. Therapeutic hypothermia decreases free radical pro- duction, inflammation, excitotoxicity and intracranial pressure, and improves cerebral metabolism after traumatic brain injury and cerebral ischemia, thus protecting against central nervous system damage. Although a series of pathological and physiological changes as well as potential side ef- fects are observed during hypothermia treatment, it remains a potential therapeutic strategy for central nervous system injuries and deserves further study.

Regeneration of the central nervous system-principles from brain regeneration in adult zebrafish

Poor recovery of neuronal functions is one of the most common healthcare challenges for patients with different types of brain injuries and/or neurodegenerative diseases.Therapeutic interventions face two major challenges:(1)How to generate neurons de novo to replenish the neuronal loss caused by injuries or neurodegeneration(restorative neurogenesis)and(2)How to prevent or limit the secondary tissue damage caused by long-term accumulation of glial cells,including microglia,at injury site(glial scar).In contrast to mammals,zebrafish have extensive regenerative capacity in numerous vital organs,including the brain,thus making them a valuable model to improve the existing therapeutic approaches for human brain repair.In response to injuries to the central nervous system(CNS),zebrafish have developed specific mechanisms to promote the recovery of the lost tissue architecture and functionality of the damaged CNS.These mechanisms include the activation of a restorative neurogenic program in a specific set of glial cells(ependymoglia)and the resolution of both the glial scar and inflammation,thus enabling proper neuronal specification and survival.In this review,we discuss the cellular and molecular mechanisms underlying the regenerative ability in the adult zebrafish brain and conclude with the potential applicability of these mechanisms in repair of the mammalian CNS.

The Olig family affects central nervous system development and disease

Neural cell differentiation and maturation is a critical step during central nervous system devel-opment. The oligodendrocyte transcription family （Olig family） is known to be an important factor in regulating neural cell differentiation. Because of this, the Olig family also affects acute and chronic central nervous system diseases, including brain injury, multiple sclerosis, and even gliomas. Improved understanding about the functions of the Olig family in central nervous system development and disease will greatly aid novel breakthroughs in central nervous system diseases. This review investigates the role of the Olig family in central nervous system develop- ment and related diseases.

涡北煤矿地面集中式降温控制系统设计与应用

针对涡北煤矿降温项目设计一套集“管”“控”为一体的集中控制系统,重点分析了该系统的网络架构、硬件组成及软件应用,详细描述了该系统实现的主要功能。提出基于BP神经网络PID控制算法对系统优化,以实现二次冷量的精准分配,达到节能减排的效果。在人机交互界面中引入3D建模技术,为矿方提供更加简洁、功能齐全、友好的人机交互界面,通过通信技术将整个降温系统的子系统全部纳入集中监控系统,提高了降温系统的生产效率,达到减员增效的效果,并预留与矿井调度通信接口,为矿井综合自动化系统提供相关基础数据。

Distribution of paired immunoglobulin-like receptor B in the nervous system related to regeneration difficulties after unilateral lumbar spinal cord injury

Paired immunoglobulin-like receptor B（Pir B） is a functional receptor of myelin-associated inhibitors for axonal regeneration and synaptic plasticity in the central nervous system, and thus suppresses nerve regeneration. The regulatory effect of Pir B on injured nerves has received a lot of attention. To better understand nerve regeneration inability after spinal cord injury, this study aimed to investigate the distribution of Pir B（via immunofluorescence） in the central nervous system and peripheral nervous system 10 days after injury. Immunoreactivity for Pir B increased in the dorsal root ganglia, sciatic nerves, and spinal cord segments. In the dorsal root ganglia and sciatic nerves, Pir B was mainly distributed along neuronal and axonal membranes. Pir B was found to exhibit a diffuse, intricate distribution in the dorsal and ventral regions. Immunoreactivity for Pir B was enhanced in some cortical neurons located in the bilateral precentral gyri. Overall, the findings suggest a pattern of Pir B immunoreactivity in the nervous system after unilateral spinal transection injury, and also indicate that Pir B may suppress repair after injury.

Central projections and connections of lumbar primary afferent fibers in adult rats:effectively revealed using Texas red-dextran amine tracing

Signals from lumbar primary afferent fibers are important for modulating locomotion of the hind-limbs.However,silver impregnation techniques,autoradiography,wheat germ agglutinin-horseradish peroxidase and cholera toxin B subunit-horseradish peroxidase cannot image the central projections and connections of the dorsal root in detail.Thus,we injected 3-k Da Texas red-dextran amine into the proximal trunks of L4 dorsal roots in adult rats.Confocal microscopy results revealed that numerous labeled arborizations and varicosities extended to the dorsal horn from T12–S4,to Clarke＇s column from T10–L2,and to the ventral horn from L1–5.The labeled varicosities at the L4 cord level were very dense,particularly in laminae I–Ⅲ,and the density decreased gradually in more rostral and caudal segments.In addition,they were predominately distributed in laminae I–IV,moderately in laminae V–VⅡ and sparsely in laminae VⅢ–X.Furthermore,direct contacts of lumbar afferent fibers with propriospinal neurons were widespread in gray matter.In conclusion,the projection and connection patterns of L4 afferents were illustrated in detail by Texas red-dextran amine-dorsal root tracing.

Neural differentiation of choroid plexus epithelial cells:role of human traumatic cerebrospinal fluid

As the key producer of cerebrospinal fluid（CSF）,the choroid plexus（CP） provides a unique protective system in the central nervous system.CSF components are not invariable and they can change based on the pathological conditions of the central nervous system.The purpose of the present study was to assess the effects of non-traumatic and traumatic CSF on the differentiation of multipotent stem-like cells of CP into the neural and/or glial cells.CP epithelial cells were isolated from adult male rats and treated with human non-traumatic and traumatic CSF.Alterations in m RNA expression of Nestin and microtubule-associated protein（MAP2）,as the specific markers of neurogenesis,and astrocyte marker glial fibrillary acidic protein（GFAP） in cultured CP epithelial cells were evaluated using quantitative real-time PCR.The data revealed that treatment with CSF（non-traumatic and traumatic） led to increase in m RNA expression levels of MAP2 and GFAP.Moreover,the expression of Nestin decreased in CP epithelial cells treated with non-traumatic CSF,while treatment with traumatic CSF significantly increased its m RNA level compared to the cells cultured only in DMEM/F12 as control.It seems that CP epithelial cells contain multipotent stem-like cells which are inducible under pathological conditions including exposure to traumatic CSF because of its compositions.

Neural regeneration by regionally induced stem cells within poststroke brains: Novel therapy perspectives for stroke patients

Ischemic stroke is a critical disease which causes serious neurological functional loss such as paresis. Hope for novel therapies is based on the increasing evidence of the presence of stem cell populations in the central nervous system (CNS) and the development of stem-cell-based therapies for stroke patients. Although mesenchymal stem cells (MSCs) represented initially a promising cell source, only a few transplanted MSCs were present near the injured areas of the CNS. Thus, regional stem cells that are present and/or induced in the CNS may be ideal when considering a treatment following ischemic stroke. In this context, we have recently showed that injury/ischemia-induced neural stem/progenitor cells (iNSPCs) and injury/ischemia-induced multipotent stem cells (iSCs) are present within post-stroke human brains and post-stroke mouse brains. This indicates that iNSPCs/iSCs could be developed for clinical applications treating patients with stroke. The present study introduces the traits of mouse and human iNSPCs, with a focus on the future perspective for CNS regenerative therapies using novel iNSPCs/iSCs.

Growth and differentiation of neural stem cells in a three-dimensional collagen gel scaffold

Collagen protein is an ideal scaffold material for the transplantation of neural stem cells. In this study rat neural stern cells were seeded into a three-dimensional collagen gel scaffold, with suspension cultured neural stem cells being used as a control group. Neural stem cells, which were cultured in medium containing epidermal growth factor and basic fibroblast growth factor, actively expanded and formed neurospheres in both culture groups. In serum-free medium conditions, the processes extended from neurospheres in the collagen gel group were much longer than those in the suspension culture group. Immunofluorescence staining showed that neurespheres cultured in collagen gels were stained positive for nestin and differentiated cells were stained positive for the neuronal marker βIII-tubulin, the astrocytic marker glial fibrillary acidic protein and the oligodendrocytic marker 2＇,3＇-cyclic nucleotide 3＇-phosphodiesterase. Compared with neurospheres cultured in suspension, the differentiation potential of neural stem cells cultured in collagen gels increased, with the formation of neurons at an early stage. Our results show that the three-dimensional collagen gel culture system is superior to suspension culture in the proliferation, differentiation and process outgrowth of neural stem cells.

中枢神经环路调节骨代谢

骨重塑是维持骨稳态(bone homeostasis)的重要过程,人们通常认为骨重塑主要接受内分泌激素调节。近年来,越来越多的证据表明,中枢神经系统通过传出神经直接参与骨稳态调节。虽然,大脑和骨骼组织之间已被证实存在明确的神经连接,但这些神经联系在大脑调节骨稳态中的作用还不十分清楚。本文将关注骨与脑之间的神经联系,分别从中枢神经系统和神经环路(neural circuit)、自主神经系统以及感觉神经系统对骨稳态的调控等方面介绍大脑调控骨代谢(bone metabolism)领域的最新进展。

星形胶质细胞来源细胞外囊泡促进大鼠神经干细胞向神经元的分化

背景:神经干细胞具有向神经元分化的潜能,已有报道表示星形胶质细胞与神经元存在密切联系,而有关星形胶质细胞来源细胞外囊泡是否具有促进神经干细胞向神经元高效分化的作用,仍未见相关报道。目的:探索星形胶质细胞来源细胞外囊泡诱导促进神经干细胞向神经元分化的可能性。方法:(1)体外培养大鼠神经干细胞及星形胶质细胞,行细胞形态及免疫荧光鉴定,进一步提取星形胶质细胞来源细胞外囊泡,并通过透射电镜、粒径分析、Western blot等方法进行鉴定;(2)将第3代神经干细胞分2组,分别加入同体积的PBS、星形胶质细胞来源细胞外囊泡(质量浓度为1 mg/mL)干预6 d;(3)通过免疫荧光、qRT-PCR和Western blot检测星形胶质细胞来源细胞外囊泡干预后神经元标志物的表达水平。结果与结论:(1)显微镜下神经干细胞形态为球形,以细胞团状分布,免疫荧光示特征性标志物CD133、Nestin呈高表达水平;(2)显微镜下星形胶质细胞形态为不规则星状,且免疫荧光示特征性标志物胶质纤维酸性蛋白呈高表达水平;(3)星形胶质细胞来源细胞外囊泡形态近似圆形或椭圆形杯状,动态光粒子散射仪显示直径在10-200 nm之间,Western blot示细胞外囊泡相关标志物CD63及TSG101表达阳性;(4)相比PBS组,星形胶质细胞来源细胞外囊泡组可见神经干细胞大量贴壁分化,分化细胞胞体饱满,有明显突起,主要呈神经元样,且微管蛋白β3及神经丝蛋白200呈高表达(P<0.05);(5)以上结果提示,星形胶质细胞来源细胞外囊泡可促进神经干细胞向神经元分化。

胚胎大鼠脑和脊髓神经干细胞的分离和培养

研究采用显微解剖、无血清细胞培养和免疫荧光细胞化学染色等实验技术 ,成功地建立了胚胎大鼠脑和脊髓神经干细胞 (NSCs)的分离和培养方法。结果显示 ,( 1)在含成纤维细胞生长因子 2 (FGF 2 )和表皮生长因子(EGF)的无血清培养液中 ,两种来源的NSCs经体外培养 8- 10代后 ,其细胞数呈指数级增加 ,其中脑来源的NSCs数由原代培养时的 1× 10 6 增加至 1× 10 12 ,脊髓来源的NSCs数从 1× 10 6 增加至 1× 10 11。增殖的细胞表达神经上皮干细胞蛋白 (nestin) ;( 2 )在含 1%胎牛血清 (FBS)的培养条件下 ,它们都能被诱导分化为神经元、少突胶质细胞和星型胶质细胞。但其分化比例可随细胞传代次数的增加而改变 ,其中 ,大脑来源的NSCs分化为神经元的比例从第二代 (P2 )的 11 95± 2 5 %下降至第五代 (P5)的 1 97± 1 16% (P <0 0 1) ,而少突胶质细胞的分化比例则基本保持不变 ,这一分化格局同样可在脊髓来源的NSCs中发现。结果表明 ,我们所分离和培养的细胞在体外经多次传代后仍具有很强的增殖能力和多向分化潜能 ,它们都表达nestin 。

“数字人脑”模型与信息处理机制研究

本文阐述了数字人脑与数字人体的关系及国内外研究概况 ,讨论了数字人脑的主要研究内容和关键科学问题 ,提出数字人脑的研究目标 ,并给出数字人脑研究的总体方案。

中枢神经系统感染性疾病的病原学研究

目的 :探讨中枢神经系统感染性疾病的病原学特点。方法 :分别用双抗体夹心ELISA法和传统的细菌及真菌培养等方法检测患者血清IgM ,IgG抗体和脑脊髓液中病原体。结果 :82 3例中枢神经系统急症患者中有 12 6例 (15 .3%)单纯疱疹病毒IgM和 /或IgG阳性 ,其中 10岁以下年龄为高峰。 10 (1.2 %)例巨细胞病毒特异性IgM和 /或IgG阳性 ;8(0 .97%)例水痘 带状疱疹病毒特异性IgM和 /或IgG阳性 ;7(0 .85 %)例为结核性脑膜炎 ;6 (0 .72 %)例为新生隐球菌性脑膜炎 ;1(0 .12 %)例为脑膜炎球菌性脑膜炎。结论 :病毒 ,特别是单纯疱疹病毒 ,是中枢神经系统感染性疾病的常见病原 ;结核杆菌和新生隐球菌感染也占一定比例。