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Differential expression of glial cell line-derived neurotrophic factor splice variants in the mouse brain 预览
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作者 Xiao-He Gu Heng Li +4 位作者 Lin Zhang Tao He Xiang Chai He Wei Dian-Shuai Gao 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期270-276,共7页
Glial cell line-derived neurotrophic factor(GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain,α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neu... Glial cell line-derived neurotrophic factor(GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain,α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neuroprotective effects on dopamine neurons. However, the expression of the GDNF splice variants in dopaminergic neurons in the brain remains unclear. Therefore, in this study, we investigated the mRNA and protein expression of α-and β-pro-GDNF in the mouse brain by real-time quantitative polymerase chain reaction, using splice variant-specific primers, and western blot analysis. At the mRNA level,β-pro-GDNF expression was significantly greater than that of α-pro-GDNF in the mouse brain. In contrast, at the protein level,α-pro-GDNF expression was markedly greater than that of β-pro-GDNF. To clarify the mechanism underlying this inverse relationship in mRNA and protein expression levels of the GDNF splice variants, we analyzed the expression of sorting protein-related receptor with A-type repeats(SorLA) by real-time quantitative polymerase chain reaction. At the mRNA level, SorLA was positively associated with β-pro-GDNF expression, but not with α-pro-GDNF expression. This suggests that the differential expression of α-and β-pro-GDNF in the mouse brain is related to SorLA expression. As a sorting protein, SorLA could contribute to the inverse relationship among the mRNA and protein levels of the GDNF isoforms. This study was approved by the Animal Ethics Committee of Xuzhou Medical University, China on July 14, 2016. 展开更多
关键词 Δ78 locus BRAIN region dopaminergic neurons glial cell line-derived NEUROTROPHIC factor mouse BRAIN precursor protein α-pro-GDNF β-pro-GDNF sorting protein-related receptor with A-TYPE REPEATS splice variants
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Microglial cathepsin B as a key driver of inflammatory brain diseases and brain aging 预览
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作者 Hiroshi Nakanishi 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第1期25-29,共5页
Interleukin-1βis a potent proinflammatory cytokine that plays a key role in the pathogenesis of the brain aging and diverse range of neurological diseases including Alzheimer’s disease,Parkinson’s disease,stroke an... Interleukin-1βis a potent proinflammatory cytokine that plays a key role in the pathogenesis of the brain aging and diverse range of neurological diseases including Alzheimer’s disease,Parkinson’s disease,stroke and persistent pain.Activated microglia are the main cellular source of interleukin-1βin the brain.Cathepsin B is associated with the production and secretion of interleukin-1βthrough pyrin domain-containing protein 3 inflammasome-independent processing of procaspase-3 in the phagolysosomes.The leakage of cathepsin B from the endosomal-lysosomal system during aging is associated with the proteolytic degradation of mitochondrial transcription factor A,which can stabilize mitochondrial DNA.Therefore,microglial cathepsin B could function as a major driver for inflammatory brain diseases and brain aging.Orally active and blood-brain barrier-permeable specific inhibitors for cathepsin B can be potentially effective new pharmaceutical interventions against inflammatory brain diseases and brain aging. 展开更多
关键词 BRAIN aging caspase-1 CATHEPSIN B INFLAMMATORY BRAIN diseases INTERLEUKIN-1Β microglia mitochondrial transcription FACTOR A neuroinflammation nuclear factor-κB oxidative stress
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Brain activation induced by different strengths of hand grasp:a functional magnetic resonance imaging study 预览
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作者 Hyeok Gyu Kwon Ju Sang Kim Mi Young Lee 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第5期875-879,共5页
Mirror neuron system can be activated by observation and execution of an action.It has an important function of action understanding.We investigated brain activations in humans by observing the strength of a hand gras... Mirror neuron system can be activated by observation and execution of an action.It has an important function of action understanding.We investigated brain activations in humans by observing the strength of a hand grasp using functional magnetic resonance imaging.Twenty right-handed healthy individuals,consisting of 10 males and 10 females,aged 22.40 ± 2.04 years,were recruited into this study from September to November 2017 via posters.Light hand grasp task video showed a hand lightly grasping and releasing a ball repeatedly.Powerful hand grasp task video showed a hand tightly grasping and releasing a ball repeatedly.Functional magnetic resonance imaging block design paradigm comprised five stimulation blocks alternating with five baseline blocks.Stimulation blocks were presented with two stimulus tasks,consisting of a light grasp and a powerful grasp.Region of interest was defined around the inferior parietal lobule,inferior frontal gyrus,and superior temporal sulcus which have been called mirror neuron system.The inferior parietal lobule,fusiform,postcentral,occipital,temporal,and frontal gyri were activated during light and powerful grasp tasks.The BOLD signal response of a powerful grasp was stronger than that of a light grasp.These results suggest that brain activation of the inferior parietal lobule,which is the core brain region of the mirror neuron system,was stronger in the powerful grasp task than in the light grasp task.We believe that our results might be helpful for instructing rehabilitation of brain injury.This study was approved by the Institutional Review Board of Daegu Oriental Hospital of Daegu Haany University on September 8,2017 (approval No.DHUMC-D-17020-PRO-01). 展开更多
关键词 BRAIN activation fMRI human BRAIN INFERIOR PARIETAL lobule light GRASP mirror NEURON system POWERFUL GRASP
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Osmotic pressure of serum and cerebrospinal fluid in patients with suspected neurological conditions 预览
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作者 Tetsuya Akaishi Toshiyuki Takahashi +3 位作者 Ichiro Nakashima Michiaki Abe Masashi Aoki Tadashi Ishii 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第5期944-947,共4页
Interstitial fluid movement in the brain parenchyma has been suggested to contribute to sustaining the metabolism in brain parenchyma and maintaining the function of neurons and glial cells.The pulsatile hydrostatic p... Interstitial fluid movement in the brain parenchyma has been suggested to contribute to sustaining the metabolism in brain parenchyma and maintaining the function of neurons and glial cells.The pulsatile hydrostatic pressure gradient may be one of the driving forces of this bulk flow.However,osmotic pressure- related factors have not been studied until now.In this prospective observational study,to elucidate the relationship between osmolality (mOsm/kg) in the serum and that in the cerebrospinal fluid (CSF),we simultaneously measured the serum and CSF osmolality of 179 subjects with suspected neurological conditions.Serum osmolality was 283.6 ± 6.5 mOsm/kg and CSF osmolality was 289.5 ± 6.6 mOsm/kg.Because the specific gravity of serum and CSF is known to be 1.024–1.028 and 1.004–1.007,respectively,the estimated average of osmolarity (mOsm/L) in the serum and CSF covered exactly the same range (i.e.,290.5–291.5 mOsm/L).There was strong correlation between CSF osmolality and serum osmolality,but the difference in osmolality between serum and CSF was not correlated with serum osmolality,serum electrolyte levels,protein levels,or quotient of albumin.In conclusion,CSF osmolarity was suggested to be equal to serum osmolarity.Osmolarity is not one of the driving forces of this bulk flow.Other factors such as hydrostatic pressure gradient should be used to explain the mechanism of bulk flow in the brain parenchyma.This study was approved by the Institutional Review Board of the Tohoku University Hospital (approval No.IRB No.2015-1-257) on July 29,2015. 展开更多
关键词 brain PARENCHYMA bulk flow CEREBROSPINAL FLUID hydrostatic PRESSURE interstitial FLUID OSMOLARITY OSMOTIC PRESSURE
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Evidence and explanation for the involvement of the nucleus accumbens in pain processing 预览
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作者 Haley N.Harris Yuan B.Peng 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期597-605,共9页
The nucleus accumbens(NAc)is a subcortical brain structure known primarily for its roles in pleasure,reward,and addiction.Despite less focus on the NAc in pain research,it also plays a large role in the mediation of p... The nucleus accumbens(NAc)is a subcortical brain structure known primarily for its roles in pleasure,reward,and addiction.Despite less focus on the NAc in pain research,it also plays a large role in the mediation of pain and is effective as a source of analgesia.Evidence for this involvement lies in the NAc’s cortical connections,functions,pharmacology,and therapeutic targeting.The NAc projects to and receives information from notable pain structures,such as the prefrontal cortex,anterior cingulate cortex,periaqueductal gray,habenula,thalamus,etc.Additionally,the NAc and other pain-modulating structures share functions involving opioid regulation and motivational and emotional processing,which each work beyond simply the rewarding experience of pain offset.Pharmacologically speaking,the NAc responds heavily to painful stimuli,due to its high density ofμopioid receptors and the activation of several different neurotransmitter systems in the NAc,such as opioids,dopamine,calcitonin gene-related peptide,γ-aminobutyric acid,glutamate,and substance P,each of which have been shown to elicit analgesic effects.In both preclinical and clinical models,deep brain stimulation of the NAc has elicited successful analgesia.The multi-functional NAc is important in motivational behavior,and the motivation for avoiding pain is just as important to survival as the motivation for seeking pleasure.It is possible,then,that the NAc must be involved in both pleasure and pain in order to help determine the motivational salience of positive and negative events. 展开更多
关键词 analgesia CIRCUITRY deep brain stimulation NOCICEPTION nucleus ACCUMBENS PAIN PAIN relief PAIN signaling REWARD STRIATUM
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Relationship between MRI perfusion and clinical severity in multiple sclerosis 预览
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作者 Maria Marcella Laganà Laura Pelizzari Francesca Baglio 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期646-652,共7页
Perfusion alterations within several brain regions have been shown in multiple sclerosis patients using different magnetic resonance imaging(MRI)techniques.Furthermore,MRI-derived brain perfusion metrics have been inv... Perfusion alterations within several brain regions have been shown in multiple sclerosis patients using different magnetic resonance imaging(MRI)techniques.Furthermore,MRI-derived brain perfusion metrics have been investigated in association with multiple sclerosis phenotypes,physical disability,and cognitive impairment.However,a review focused on these aspects is still missing.Our aim was to review all the studies investigating the relationship between perfusion MRI and clinical severity during the last fifteen years to understand the clinical relevance of these findings.Perfusion differences among phenotypes were observed both with 1.5T and 3T scanners,with progressive multiple sclerosis presenting with lower perfusion values than relapsing-remitting multiple sclerosis patients.However,only 3T scanners showed a statistically significant distinction.Controversial results about the association between MRI-derived perfusion metrics and physical disability scores were found.However,the majority of the studies showed that lower brain perfusion and longer transit time are associated with more severe physical disability and worse cognitive performances. 展开更多
关键词 brain PERFUSION cerebral blood flow COGNITION DISABILITY magnetic resonance imaging MRI multiple SCLEROSIS PHENOTYPES progressive relapsing remitting
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Inhibiting endogenous tissue plasminogen activator enhanced neuronal apoptosis and axonal injury after traumatic brain injury 预览
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作者 Jun-Jie Zhao Zun-Wei Liu +4 位作者 Bo Wang Ting-Qin Huang Dan Guo Yong-Lin Zhao Jin-Ning Song 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期667-675,共9页
Tissue plasminogen activator is usually used for the treatment of acute ischemic stroke,but the role of endogenous tissue plasminogen activator in traumatic brain injury has been rarely reported.A rat model of traumat... Tissue plasminogen activator is usually used for the treatment of acute ischemic stroke,but the role of endogenous tissue plasminogen activator in traumatic brain injury has been rarely reported.A rat model of traumatic brain injury was established by weight-drop method.The tissue plasminogen activator inhibitor neuroserpin(5μL,0.25 mg/mL)was injected into the lateral ventricle.Neurological function was assessed by neurological severity score.Neuronal and axonal injuries were assessed by hematoxylin-eosin staining and Bielschowsky silver staining.Protein level of endogenous tissue plasminogen activator was analyzed by western blot assay.Apoptotic marker cleaved caspase-3,neuronal marker neurofilament light chain,astrocyte marker glial fibrillary acidic protein and microglial marker Iba-1 were analyzed by immunohistochemical staining.Apoptotic cell types were detected by immunofluorescence double labeling.Apoptotic cells in the damaged cortex were detected by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling staining.Degenerating neurons in the damaged cortex were detected by Fluoro-Jade B staining.Expression of tissue plasminogen activator was increased at 6 hours,and peaked at 3 days after traumatic brain injury.Neuronal apoptosis and axonal injury were detected after traumatic brain injury.Moreover,neuroserpin enhanced neuronal apoptosis,neuronal injury and axonal injury,and activated microglia and astrocytes.Neuroserpin further deteriorated neurobehavioral function in rats with traumatic brain injury.Our findings confirm that inhibition of endogenous tissue plasminogen activator aggravates neuronal apoptosis and axonal injury after traumatic brain injury,and activates microglia and astrocytes.This study was approved by the Biomedical Ethics Committee of Animal Experiments of Shaanxi Province of China in June 2015. 展开更多
关键词 apoptosis ASTROCYTES AXONAL INJURY inflammation microglia nerve REGENERATION neural REGENERATION neuronal INJURY neurons NEUROSERPIN tissue PLASMINOGEN activator traumatic brain INJURY
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Inflammation-related gene expression profiles of salivary extracellular vesicles in patients with head trauma 预览
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作者 Yan Cheng Mandy Pereira +10 位作者 Neha P.Raukar John L.Reagan Mathew Quesenberry Laura Goldberg Theodor Borgovan W Curt LaFrance Jr Mark Dooner Maria Deregibus Giovanni Camussi Bharat Ramratnam Peter Quesenberry 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第4期676-681,共6页
At present,there is no reliable biomarker for the diagnosis of traumatic brain injury(TBI).Studies have shown that extracellular vesicles released by damaged cells into biological fluids can be used as potential bioma... At present,there is no reliable biomarker for the diagnosis of traumatic brain injury(TBI).Studies have shown that extracellular vesicles released by damaged cells into biological fluids can be used as potential biomarkers for diagnosis of TBI and evaluation of TBI severity.We hypothesize that the genetic profile of salivary extracellular vesicles in patients with head trauma differs from that in uninjured subjects.Findings from this hypothesis would help investigate the severity of TBI.This study included 19 subjects,consisting of seven healthy controls who denied history of head trauma,six patients diagnosed with concussion injury from an outpatient concussion clinic,and six patients with TBI who received treatment in the emergency department within 24 hours after injury.Real-time PCR analysis of salivary extracellular vesicles in participants was performed using TaqMan Human Inflammation array.Gene expression analysis revealed nine upregulated genes in emergency department patients(LOX5,ANXA3,CASP1,IL2RG,ITGAM,ITGB2,LTA4H,MAPK14,and TNFRSF1A)and 13 upregulated genes in concussion clinic patients compared with healthy participants(ADRB1,ADRB2,BDKRB1,HRH1,HRH2,LTB4R2,LTB4R,PTAFR,CYSLTR1,CES1,KLK1,MC2R,and PTGER3).Each patient group had a unique profile.Comparison between groups showed that 15 inflammation-related genes had significant expression change.Our results indicate that inflammation biomarkers can be used for diagnosis of TBI and evaluation of disease severity.This study was approved by the Institutional Review Board on December 18,2015(approval No.0078-12)and on June 9,2016(approval No.4093-16). 展开更多
关键词 chronic TRAUMATIC encephalopathy emergency department extracellular vesicles INFLAMMATION OUTPATIENT CONCUSSION clinic real-time PCR analysis SALIVA TRAUMATIC brain injury
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Bone marrow-derived mesenchymal stem cell transplantation attenuates overexpression of inflammatory mediators in rat brain after cardiopulmonary resuscitation 预览
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作者 Qing-Ming Lin Xia-Hong Tang +2 位作者 Shi-Rong Lin Ben-Dun Chen Feng Chen 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期324-331,共8页
Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation;however, the precise mechanisms remain un... Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation;however, the precise mechanisms remain unclear. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cell treatment on expression profiles of multiple cytokines in the brain after cardiac arrest and cardiopulmonary resuscitation. Cardiac arrest was induced in rats by asphyxia and cardiopulmonary resuscitation was initiated 6 minutes after cardiac arrest. One hour after successful cardiopulmonary resuscitation, rats were injected with either phosphate-buffered saline(control) or 1 × 10~6 bone marrow-derived mesenchymal stem cells via the tail vein. Serum S100 B levels were measured by enzyme-linked immunosorbent assay and neurological deficit scores were evaluated to assess brain damage at 3 days after cardiopulmonary resuscitation. Serum S100 B levels were remarkably decreased and neurological deficit scores were obviously improved in the mesenchymal stem cell group compared with the phosphate-buffered saline group. Brains were isolated from the rats and expression levels of 90 proteins were determined using a RayBio Rat Antibody Array, to investigate the cytokine profiles. Brain levels of the inflammatory mediators tumor necrosis factor-α, interferon-γ, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, macrophage inflammatory protein-3α, macrophage-derived chemokine, and matrix metalloproteinase-2 were decreased ≥ 1.5-fold, while levels of the anti-inflammatory factor interleukin-10 were increased ≥ 1.5-fold in the mesenchymal stem cell group compared with the control group. Donor mesenchymal stem cells were detected by immunofluorescence to determine their distribution in the damaged brain, and were primarily observed in the cerebral cortex. These results indicate that bone marrow-derived mesenchymal stem cell transplantation attenuates brain damage induced by cardiac arrest and 展开更多
关键词 antibody array ASPHYXIA brain damage cardiac arrest CARDIOPULMONARY RESUSCITATION global cerebral ischemia inflammatory mediator mesenchymal stem cell NEUROLOGICAL DEFICIT score S100B
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Adult neurogenesis from reprogrammed astrocytes 预览
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作者 Brian B.Griffiths Anvee Bhutani Creed MStary 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第6期973-979,共7页
The details of adult neurogenesis,including environmental triggers,region specificity,and species homology remain an area of intense investigation.Slowing or halting age-related cognitive dysfunction,or restoring neur... The details of adult neurogenesis,including environmental triggers,region specificity,and species homology remain an area of intense investigation.Slowing or halting age-related cognitive dysfunction,or restoring neurons lost to disease or injury represent just a fraction of potential therapeutic applications.New neurons can derive from stem cells,pluripotent neural progenitor cells,or non-neuronal glial cells,such as astrocytes.Astrocytes must be epigenetically"reprogrammed"to become neurons,which can occur both naturally in vivo,and via artificial exogenous treatments.While neural progenitor cells are localized to a few neurogenic zones in the adult brain,astrocytes populate almost every brain structure.In this review,we will summarize recent research into neurogenesis that arises from conversion of post-mitotic astrocytes,detail the genetic and epigenetic pathways that regulate this process,and discuss the possible clinical relevance in supplementing stem-cell neurogenic therapies. 展开更多
关键词 ASTROCYTE brain DEDIFFERENTIATION development disease GLIA INJURY NEUROGENESIS
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Hydrogels for neuroprotection and functional rewiring:a new era for brain engineering 预览
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作者 Rocío Fernández-Serra Rebeca Gallego +1 位作者 Paloma Lozano Daniel González-Nieto 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第5期783-789,共7页
The neurological devastation of neurodegenerative and cerebrovascular diseases reinforces our perseverance to find advanced treatments to deal with these fatal pathologies.High-performance preclinical results have fai... The neurological devastation of neurodegenerative and cerebrovascular diseases reinforces our perseverance to find advanced treatments to deal with these fatal pathologies.High-performance preclinical results have failed at clinical level,as it has been the case for a wide variety of neuroprotective agents and cell-based therapies employed to treat high prevalent brain pathologies such as stroke,Alzheimer’s and Parkinson’s diseases.An unquestionable reality is the current absence of effective therapies to neuroprotect the brain,to arrest neurodegeneration and rewire the impaired brain circuits.Part of the problem might arise from the lack of adequate in vitro and in vivo models and that most of the underlying pathophysiological mechanisms are not yet clarified.Another contributing factor is the lack of efficient systems to sustain drug release at therapeutic concentrations and enhance the survival and function of grafted cells in transplantation procedures.For medical applications the use of biomaterials of different compositions and formats has experienced a boom in the last decades.Although the greater complexity of central nervous system has probably conditioned their extensive use with respect to other organs,the number of biomaterials-based applications to treat the injured brain or in the process of being damaged has grown exponentially.Hydrogel-based biomaterials have constituted a turning point in the treatment of cerebral disorders using a new form of advanced therapy.Hydrogels show mechanical properties in the range of cerebral tissue resulting very suitable for local implantation of drugs and cells.It is also possible to fabricate three-dimensional hydrogel constructs with adaptable mesh size to facilitate axonal guidance and elongation.Along this article,we review the current trends in this area highlighting the positive impact of hydrogel-based biomaterials over the exhaustive control of drug delivery,cell engraftment and axonal reinnervation in brain pathologies. 展开更多
关键词 advanced therapies Alzheimer’s DISEASE biomaterials BRAIN HYDROGELS NEUROLOGICAL diseases Parkinson’s DISEASE polymers stroke
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Circular RNAs in early brain development and their influence and clinical significance in neuropsychiatric disorders 预览
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作者 Chuan-Jun Zhuo Wei-Hong Hou +5 位作者 De-Guo Jiang Hong-Jun Tian Li-Na Wang Feng Jia Chun-Hua Zhou Jing-Jing Zhu 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第5期817-823,共7页
Neuropsychiatric disorders represent a set of severe and complex mental illnesses,and the exact etiologies of which are unknown.It has been well documented that impairments in the early development of the brain contri... Neuropsychiatric disorders represent a set of severe and complex mental illnesses,and the exact etiologies of which are unknown.It has been well documented that impairments in the early development of the brain contribute to the pathogenesis of many neuropsychiatric disorders.Currently,the diagnosis of neuropsychiatric disorders largely relies on subjective cognitive assessment,because there are no widely accepted biochemical or genetic biomarkers for diagnosing mental illness.Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA (ncRNA) with a closed-loop structure.In recent years,there have been tremendous advances in our understanding of the expression profiles and biological roles of circRNAs.In the brain,circRNAs are particularly enriched and are expressed more abundantly in contrast to linear counterpart transcripts.They are highly active at neuronal synapses.These features make circRNAs uniquely crucial for understanding brain health,disease,and neuropsychiatric disorders.This review focuses on the role of circRNAs in early brain development and other brain-related processes that have been associated with the development of neuropsychiatric disorders.In addition,we discuss the potential for blood or cerebrospinal fluid circRNAs to be used as novel biomarkers in the early diagnosis of neuropsychiatric disorders.The findings reviewed here may provide new insight into the pathological mechanisms underlying the onset and progression of neuropsychiatric disorders. 展开更多
关键词 AUTISM spectrum DISORDERS bipolar disorder brain exosomal circRNAs microRNAs nerve regeneration NON-CODING RNAS OBSESSIVE-COMPULSIVE DISORDERS SCHIZOPHRENIA
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Dietary habits,lifestyle factors and neurodegenerative diseases 预览
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作者 Aurel Popa-Wagner Dinu Iuliu Dumitrascu +4 位作者 Bogdan Capitanescu Eugen Bogdan Petcu Roxana Surugiu Wen-Hui Fang Danut-Adrian Dumbrava 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第3期394-400,共7页
Worldwide stroke is increasing in parallel with modernization,changes in lifestyle,and the growing elderly population.Our review is focused on the link between diet,as part of‘modern lifestyle’,and health in the con... Worldwide stroke is increasing in parallel with modernization,changes in lifestyle,and the growing elderly population.Our review is focused on the link between diet,as part of‘modern lifestyle’,and health in the context of genetic predisposition of individuals to‘unhealthy’metabolic pathway activity.It is concluded that lifestyle including high sugar diets,alcohol and tobacco addiction or high fat diets as well as ageing,brain injury,oxidative stress and neuroinflammation,negatively influence the onset,severity and duration of neurodegenerative diseases.Fortunately,there are several healthy dietary components such as polyunsaturated fatty acids and the anti-oxidants curcumin,resveratrol,blueberry polyphenols,sulphoraphane,salvionic acid as well as caloric restriction and physical activity,which may counteract ageing and associated neurodegenerative diseases via increased autophagy or increased neurogenesis in the adult brain. 展开更多
关键词 brain injury DIETARY HABITS LIFESTYLE metaflammation NEURODEGENERATION OXIDATIVE stress type 2 diabetes MELLITUS
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RIP3/MLKL-mediated neuronal necroptosis induced by methamphetamine at 39℃ 预览
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作者 Li-Min Guo Zhen Wang +8 位作者 Shi-Ping Li Mi Wang Wei-Tao Yan Feng-Xia Liu Chu-Dong Wang Xu-Dong Zhang Dan Chen Jie Yan Kun Xiong 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第5期865-874,共10页
Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism under... Methamphetamine is one of the most prevalent drugs abused in the world.Methamphetamine abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric symptoms.However,the detailed mechanism underlying its neurotoxic action remains elusive.This study investigated the effects of methamphetamine + 39℃ on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats.Primary cortex neurons were exposed to 1 mM methamphetamine + 39℃.Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39℃ triggered obvious necrosis-like death in cultured primary cortical neurons,which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially.Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39℃ for 3 hours.After pre-treatment with RIP3 inhibitor GSK’872,propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased;RIP3 and MLKL protein expression significantly decreased.Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse.Taken together,the above results suggest that methamphetamine + 39℃ can induce RIP3/MLKL regulated necroptosis,thereby resulting in neurotoxicity.The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University,China (approval numbers: 2017-S026 and 2017-S033) on March 7,2017. 展开更多
关键词 GSK'872 human brain tissue hyperpyrexia METHAMPHETAMINE mixed LINEAGE kinase domain-like protein necrostatin-1 NECROPTOSIS nerve REGENERATION neural REGENERATION rat CORTICAL neurons receptor-interacting protein-3 synergistic effect
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Selective brain hypothermia-induced neuroprotection against focal cerebral ischemia/reperfusion injury is associated with Fis1 inhibition 预览
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作者 Ya-Nan Tang Gao-Feng Zhang +6 位作者 Huai-Long Chen Xiao-Peng Sun Wei-Wei Qin Fei Shi Li-Xin Sun Xiao-Na Xu Ming-Shan Wang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第5期903-911,共9页
Selective brain hypothermia is considered an effective treatment for neuronal injury after stroke,and avoids the complications of general hypothermia.However,the mechanisms by which selective brain hypothermia affects... Selective brain hypothermia is considered an effective treatment for neuronal injury after stroke,and avoids the complications of general hypothermia.However,the mechanisms by which selective brain hypothermia affects mitochondrial fission remain unknown.In this study,we investigated the effect of selective brain hypothermia on the expression of fission 1 (Fis1) protein,a key factor in the mitochondrial fission system,during focal cerebral ischemia/reperfusion injury.Sprague-Dawley rats were divided into four groups.In the sham group,the carotid arteries were exposed only.In the other three groups,middle cerebral artery occlusion was performed using the intraluminal filament technique.After 2 hours of occlusion,the filament was slowly removed to allow blood reperfusion in the ischemia/reperfusion group.Saline,at 4℃ and 37℃,were perfused through the carotid artery in the hypothermia and normothermia groups,respectively,followed by restoration of blood flow.Neurological function was assessed with the Zea Longa 5-point scoring method.Cerebral infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride staining,and apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining.Fis1 and cytosolic cytochrome c levels were assessed by western blot assay.Fis1 mRNA expression was assessed by quantitative reverse transcription-polymerase chain reaction.Mitochondrial ultrastructure was evaluated by transmission electron microscopy.Compared with the sham group,apoptosis,Fis1 protein and mRNA expression and cytosolic cytochrome c levels in the cortical ischemic penumbra and cerebral infarct volume were increased after reperfusion in the other three groups.These changes caused by cerebral ischemia/reperfusion were inhibited in the hypothermia group compared with the normothermia group.These findings show that selective brain hypothermia inhibits Fis1 expression and reduces apoptosis,thereby ameliorating focal cerebral ischemia/reperfusion injury in rats.Experiments were auth 展开更多
关键词 apoptosis Fis1 HYPOTHERMIA ISCHEMIA/REPERFUSION injury mitochondria MITOCHONDRIAL fission MITOCHONDRIAL ultrastructure NEUROPROTECTION SELECTIVE BRAIN HYPOTHERMIA stroke
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Hypoxia-ischemia in the immature rodent brain impairs serotonergic neuronal function in certain dorsal raphénuclei 预览
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作者 Hanna EReinebrant Julie A.Wixey Kathryn M.Buller 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第3期457-463,共7页
Neonatal hypoxia-ischemia(HI)results in losses of serotonergic neurons in specific dorsal raphe nuclei.However,not all serotonergic raphe neurons are lost and it is therefore important to assess the function of remain... Neonatal hypoxia-ischemia(HI)results in losses of serotonergic neurons in specific dorsal raphe nuclei.However,not all serotonergic raphe neurons are lost and it is therefore important to assess the function of remaining neurons in order to understand their potential to contribute to neurological disorders in the HI-affected neonate.The main objective of this study was to determine how serotonergic neurons,remaining in the dorsal raphe nuclei after neonatal HI,respond to an external stimulus(restraint stress).On postnatal day 3(P3),male rat pups were randomly allocated to one of the following groups:(i)control+no restraint(n=5),(ii)control+restraint(n=6),(iii)P3 HI+no restraint(n=5)or(iv)P3 HI+restraint(n=7).In the two HI groups,rat pups underwent surgery to ligate the common carotid artery and were then exposed to 6%O2 for 30 minutes.Six weeks after P3 HI,on P45,rats were subjected to restraint stress for 30 minutes.Using dual immunolabeling for Fos protein,a marker for neuronal activity,and serotonin(5-hydroxytrypamine;5-HT),numbers of Fos-positive 5-HT neurons were determined in five dorsal raphe nuclei.We found that restraint stress alone increased numbers of Fos-positive 5-HT neurons in all five dorsal raphe nuclei compared to control animals.However,following P3 HI,the number of stress-induced Fos-positive 5-HT neurons was decreased significantly in the dorsal raphe ventrolateral,interfascicular and ventral nuclei compared with control animals exposed to restraint stress.In contrast,numbers of stress-induced Fos-positive 5-HT neurons in the dorsal raphe dorsal and caudal nuclei were not affected by P3 HI.These data indicate that not only are dorsal raphe serotonergic neurons lost after neonatal HI,but also remaining dorsal raphe serotonergic neurons have reduced differential functional viability in response to an external stimulus.Procedures were approved by the University of Queensland Animal Ethics Committee(UQCCR958/08/NHMRC)on February 27,2009. 展开更多
关键词 DORSAL RAPHE NUCLEI Fos HYPOXIA-ISCHEMIA neonate newborn BRAIN injury preterm restraint stress serotonin
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Transfer of mitochondria from mesenchymal stem cells derived from induced pluripotent stem cells attenuates hypoxia-ischemia-induced mitochondrial dysfunction in PC12 cells 预览
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作者 Yan Yang Gen Ye +5 位作者 Yue-Lin Zhang Hai-Wei He Bao-Qi Yu Yi-Mei Hong Wei You Xin Li 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第3期464-472,共9页
Mitochondrial dysfunction in neurons has been implicated in hypoxia-ischemia-induced brain injury.Although mesenchymal stem cell therapy has emerged as a novel treatment for this pathology,the mechanisms are not fully... Mitochondrial dysfunction in neurons has been implicated in hypoxia-ischemia-induced brain injury.Although mesenchymal stem cell therapy has emerged as a novel treatment for this pathology,the mechanisms are not fully understood.To address this issue,we first co-cultured 1.5×10^5 PC12 cells with mesenchymal stem cells that were derived from induced pluripotent stem cells at a ratio of 1:1,and then intervened with cobalt chloride(CoCl2)for 24 hours.Reactive oxygen species in PC12 cells was measured by Mito-sox.Mitochondrial membrane potential(ΔΨm)in PC12 cells was determined by JC-1 staining.Apoptosis of PC12 cells was detected by terminal deoxynucleotidal transferase-mediated dUTP nick end-labeling staining.Mitochondrial morphology in PC12 cells was examined by transmission electron microscopy.Transfer of mitochondria from the mesenchymal stem cells derived from induced pluripotent stem cells to damaged PC12 cells was measured by flow cytometry.Mesenchymal stem cells were induced from pluripotent stem cells by lentivirus infection containing green fluorescent protein in mitochondria.Then they were co-cultured with PC12 cells in Transwell chambers and treated with CoCl2 for 24 hours to detect adenosine triphosphate level in PC12 cells.CoCl2-induced PC12 cell damage was dose-dependent.Co-culture with mesenchymal stem cells significantly reduced apoptosis and restoredΔΨm in the injured PC12 cells under CoCl2 challenge.Co-culture with mesenchymal stem cells ameliorated mitochondrial swelling,the disappearance of cristae,and chromatin margination in the injured PC12 cells.After direct co-culture,mitochondrial transfer from the mesenchymal stem cells stem cells to PC12 cells was detected via formed tunneling nanotubes between these two types of cells.The transfer efficiency was greatly enhanced in the presence of CoCl2.More importantly,inhibition of tunneling nanotubes partially abrogated the beneficial effects of mesenchymal stem cells on CoCl2-induced PC12 cell injury.Mesenchymal stem cells reduced CoCl2-induced 展开更多
关键词 apoptosis brain injury HYPOXIA-ISCHEMIA INDUCED pluripotent STEM CELLS mesenchymal STEM CELLS MITOCHONDRIAL membrane potential MITOCHONDRIAL TRANSFER PC12 CELLS tunneling nanotubes
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Human Brain Slice Culture: A Useful Tool to Study Brain Disorders and Potential Therapeutic Compounds
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作者 Xin-Rui Qi Ronald W.H.Verwer +4 位作者 Ai-Min Bao Rawien A.Balesar Sabina Luchetti Jiang-Ning Zhou Dick F.Swaab 《神经科学通报:英文版》 SCIE CAS CSCD 2019年第2期244-252,共9页
Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary... Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary cell cultures may provide useful tools to study certain aspects of brain disorders. However, discrepancies among these studies or unsuccessful translation from animal/cell studies to human/clinical studies often occur, because these models generally represent only some symptoms of a neuropsychiatric disorder rather than the complete disorder. Human brain slice cultures from postmortem tissue or resected tissue from operations have shown that, in vitro, neurons and glia can stay alive for long periods of time, while their morphological and physiological characteristics, and their ability to respond to experimental manipulations are maintained. Human brain slices can thus provide a close representation of neuronal networks in vivo, be a valuable tool for investigation of the basis of neuropsychiatric disorders, and provide a platform for the evaluation of novel pharmacological treatments of human brain diseases.A brain bank needs to provide the necessary infrastructure to bring together donors, hospitals, and researchers who want to investigate human brain slices in cultures of clinically and neuropathologically well-documented material. 展开更多
关键词 Alzheimer’s disease BRAIN bank Brain-derived neurotrophic factor Depression Electrical activity HUMAN BRAIN slice CULTURE Neuropsychiatric disorders ORGANOTYPIC CULTURE POSTMORTEM HUMAN BRAIN TISSUE Resected HUMAN BRAIN TISSUE
Brain Banking for Research into Neurodegenerative Disorders and Ageing
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作者 Claire E.Shepherd Holly Alvendia Glenda M.Halliday 《神经科学通报:英文版》 SCIE CAS CSCD 2019年第2期283-288,共6页
Advances in cellular and molecular biology underpin most current therapeutic advances in medicine.Such advances for neurological and neurodegenerative diseases are hindered by the lack of similar specimens. It is beco... Advances in cellular and molecular biology underpin most current therapeutic advances in medicine.Such advances for neurological and neurodegenerative diseases are hindered by the lack of similar specimens. It is becoming increasingly evident that greater access to human brain tissue is necessary to understand both the cellular biology of these diseases and their variation. Research in these areas is vital to the development of viable therapeutic options for these currently untreatable diseases. The development and coordination of human brain specimen collection through brain banks is evolving. This perspective article from the Sydney Brain Bank reviews data concerning the best ways to collect and store material for different research purposes. 展开更多
关键词 BRAIN BANKING BRAIN DONATION NEURODEGENERATIVE DISEASES Human BRAIN TISSUE processing
脑科学研究——生命科学最大的挑战 预览
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作者 孙涛 李信晓 《宁夏医科大学学报》 2019年第1期1-6,共6页
随着社会、经济的发展及人们认知的提高,脑科学研究已成为全世界科学研究的热点之一。新兴技术的出现极大促进了脑科学研究,为揭示大脑功能、运作机制和治疗脑疾病方面起到了重要作用。通过脑科学的基础研究、临床研究和基于脑研究大数... 随着社会、经济的发展及人们认知的提高,脑科学研究已成为全世界科学研究的热点之一。新兴技术的出现极大促进了脑科学研究,为揭示大脑功能、运作机制和治疗脑疾病方面起到了重要作用。通过脑科学的基础研究、临床研究和基于脑研究大数据信息的挖掘,为类脑研究项目的开展奠定了基础。同时,脑的发育与衰老、学习与记忆、认知与情绪、意识与精神及各脑区的结构功能研究成为人类不断认识世界、认识自我、超越自我的最终挑战。脑科学研究被称为生命科学最后的疆域,是现代认知科学乃至整个生命科学面临的最大挑战,因此,脑科学研究对提高人们的健康水平、生活质量和创新能力具有重要的现实意义。 展开更多
关键词 大脑 人类脑计划 脑区 人工智能
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