Objective To investigate the difference in tumor conventional imaging findings and texture features on T2 weighted images between glioblastoma and primary central neural system(CNS) lymphoma. Methods The pre-operative...Objective To investigate the difference in tumor conventional imaging findings and texture features on T2 weighted images between glioblastoma and primary central neural system(CNS) lymphoma. Methods The pre-operative MRI data of 81 patients with glioblastoma and 28 patients with primary CNS lymphoma admitted to the Chinese PLA General Hospital and Hainan Hospital of Chinese PLA General Hospital were retrospectively collected. All patients underwent plain MR imaging and enhanced T1 weighted imaging to visualize imaging features of lesions. Texture analysis of T2 weighted imaging(T2 WI) was performed by use of GLCM texture plugin of ImageJ software, and the texture parameters including Angular Second Moment(ASM), Contrast, Correlation, Inverse Difference Moment(IDM), and Entropy were measured. Independent sample t-test and Mann-Whitney U test were performed for the between-group comparisons, regression model was established by Binary Logistic regression analysis, and receiver operating characteristic(ROC) curve was plotted to compare the diagnostic efficacy. Results The conventional imaging features including cystic and necrosis changes(P = 0.000), ‘Rosette' changes(P = 0.000) and ‘incision sign'(P = 0.000), except ‘flame-like edema'(P = 0.635), presented significantly statistical difference between glioblastoma and primary CNS lymphoma. The texture features, ASM, Contrast, Correlation, IDM and Entropy, showed significant differences between glioblastoma and primary CNS lympoma(P = 0.006,0.000, 0.002, 0.000, and 0.015 respectively). The area under the ROC curve was 0.671, 0.752, 0.695, 0.720 and 0.646 respectively, and the area under the ROC curve was 0.917 for the combined texture variables(Contrast, cystic and necrosis, ‘Rosette' changes, and ‘incision sign') in the model of Logistic regression. Binary Logistic regression analysis demonstrated that cystic and necrosis changes, ‘Rosette' changes and ‘incision sign' and texture Contrast could be considered as the specific texture variables for the differential diagnosis of glioblastoma and primary CNS lymphoma. Conclusion The texture features of T2 WI and conventional imaging findings may be used to distinguish glioblastoma from primary CNS lymphoma.展开更多
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 cen...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.展开更多
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, p...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.展开更多
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-transc...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.展开更多
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 ca...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.展开更多
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 ...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.展开更多
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 ef...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.展开更多
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, excitotoxi...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.展开更多
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 challe...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.展开更多
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 neura...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.展开更多
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 pathologi...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.展开更多
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 cen...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.展开更多
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 regenera...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.展开更多
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 tox...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.展开更多
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 ne...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.展开更多
文摘Objective To investigate the difference in tumor conventional imaging findings and texture features on T2 weighted images between glioblastoma and primary central neural system(CNS) lymphoma. Methods The pre-operative MRI data of 81 patients with glioblastoma and 28 patients with primary CNS lymphoma admitted to the Chinese PLA General Hospital and Hainan Hospital of Chinese PLA General Hospital were retrospectively collected. All patients underwent plain MR imaging and enhanced T1 weighted imaging to visualize imaging features of lesions. Texture analysis of T2 weighted imaging(T2 WI) was performed by use of GLCM texture plugin of ImageJ software, and the texture parameters including Angular Second Moment(ASM), Contrast, Correlation, Inverse Difference Moment(IDM), and Entropy were measured. Independent sample t-test and Mann-Whitney U test were performed for the between-group comparisons, regression model was established by Binary Logistic regression analysis, and receiver operating characteristic(ROC) curve was plotted to compare the diagnostic efficacy. Results The conventional imaging features including cystic and necrosis changes(P = 0.000), ‘Rosette' changes(P = 0.000) and ‘incision sign'(P = 0.000), except ‘flame-like edema'(P = 0.635), presented significantly statistical difference between glioblastoma and primary CNS lymphoma. The texture features, ASM, Contrast, Correlation, IDM and Entropy, showed significant differences between glioblastoma and primary CNS lympoma(P = 0.006,0.000, 0.002, 0.000, and 0.015 respectively). The area under the ROC curve was 0.671, 0.752, 0.695, 0.720 and 0.646 respectively, and the area under the ROC curve was 0.917 for the combined texture variables(Contrast, cystic and necrosis, ‘Rosette' changes, and ‘incision sign') in the model of Logistic regression. Binary Logistic regression analysis demonstrated that cystic and necrosis changes, ‘Rosette' changes and ‘incision sign' and texture Contrast could be considered as the specific texture variables for the differential diagnosis of glioblastoma and primary CNS lymphoma. Conclusion The texture features of T2 WI and conventional imaging findings may be used to distinguish glioblastoma from primary CNS lymphoma.
基金the Medical Research Foundation of Guangdong Province, No.A2005707
文摘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.
基金supported by the Leibniz Association,Germany,and the VELUX Foundation,Switzerland
文摘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.
基金supported by the National Natural Science Foundation of China,No.81401084(to XHW)Beijing Municipal Administration of Hospital Ascent Plan,No.DFL20150802(to TLW)+2 种基金Beijing 215 High Level Healthcare Talent Plan Academic Leader,No.008-0027(to TLW)Beijing Municipal Commission of Health and Family Planning,No.PXM2017_026283_000002(to TLW)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding,No.ZYLX201706(to TLW)
文摘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.
文摘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.
基金supported by a grant from the National Natural Science Foundation of ChinaNo.8147108781170577
文摘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.
基金supported by Onassis Foundation(to MT)the National Center for Complementary and Integrative Health(NCCIH),No.R21AT008865(to NM)National Institute of Aging(NIA)/National Institute of Mental Health(NIMH),No.R01AG042512(to NM)
文摘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.
文摘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.
基金Supported by the German Research foundation(DFG),No.SFB 870
文摘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.
基金the National Natural Science Foundation of China,No.81171859the Natural Science Foundation of Chongqing,No.cstc2012jjA10058the Chongqing Health Bureau Project,No.2011-2-172
文摘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.
文摘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.
基金Supported by Japan Society for the Promotion of Science(JSPS)KAKENHI,No.15K06723 and No.18K07380
文摘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.
基金supported by the National Natural Science Foundation of China,No.81171178the Natural Science Foundation of Shanxi Province in China,No.2012011036-3the Research Project of Shanxi Scholarship Council of China,No.2012-047
文摘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.
基金supported by the Medical Sciences Foundation of China,No.14CXZ007
文摘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.
文摘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.