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| 1 | Neuronal autophagy aggravates microglial inflammatory injury by downregulating CX3CL1/fractalkine after ischemic stroke显示文摘Ischemic stroke often induces excessive neuronal autophagy, resulting in brain damage; meanwhile, inflammatory responses stimulated by ischemia exacerbate neural injury. However, interactions between neuronal autophagy and microglial inflammation following ischemic stroke are poorly understood. CX3CL1/fractalkine, a membrane-bound chemokine expressed on neurons, can suppress microglial inflammation by binding to its receptor CX3CR1 on microglia. In the present study, to investigate whether autophagy could alter CX3CL1 expression on neurons and consequently change microglial inflammatory activity, middle cerebral artery occlusion(MCAO) was established in Sprague-Dawley rats to model ischemic stroke, and tissues from the ischemic penumbra were obtained to evaluate autophagy level and microglial inflammatory activity. MCAO rats were administered 3-methyladenine(autophagy inhibitor) or Tat-Beclin 1(autophagy inducer). Western blot assays were conducted to quantify expression of Beclin-1, nuclear factor kappa Bp65(NF-κB), light chain 3B(LC3B), and CX3CL1 in ischemic penumbra. Moreover, immunofluorescence staining was performed to quantify numbers of LC3B-, CX3CL1-, and Iba-1-positive cells in ischemic penumbra. In addition, enzyme linked immunosorbent assays were utilized to analyze concentrations of tumor necrosis factor alpha(TNF-α), interleukin 6(IL-6), interleukin 1 beta(IL-1β), and prostaglandin E2(PGE2). A dry/wet weight method was used to detect brain water content, while 2,3,5,-triphenyltetrazolium chloride staining was utilized to measure infarct volume. The results demonstrated that autophagy signaling(Beclin-1 and LC3B expression) in penumbra was prominently activated by MCAO, while CX3CL1 expression on autophagic neurons was significantly reduced and microglial inflammation was markedly activated. However, after inhibition of autophagy signaling with 3-methyladenine, CX3CL1 expression on neurons was obviously increased, whereas Iba-1 and NF-κB expression was downregulated; TNF-α, IL-6, IL-1β, and PGE2 levels were decreased; and cerebral edema was obviously mitigated. In contrast, after treatment with the autophagy inducer Tat-Beclin 1, CX3CL1 expression on neurons was further reduced; Iba-1 and NF-κB expression was increased; TNF-α, IL-6, IL-1β, and PGE2 levels were enhanced; and cerebral edema was aggravated. Our study suggests that ischemia-induced neuronal autophagy facilitates microglial inflammatory injury after ischemic stroke, and the efficacy of this process may be associated with downregulated CX3CL1 expression on autophagic neurons. | Hong-Yun He Lu Ren Tao Guo Yi-Hao Deng | 2019 | Neural Regeneration Research2019，14，2： | 25 |
| 2 | Interplay between inflammation,immune system and neuronal pathways:Effect on gastrointestinal motility显示文摘Sepsis is a systemic inflammatory response representing the leading cause of death in critically ill patients,mostly due to multiple organ failure.The gastrointestinal tract plays a pivotal role in the pathogenesis of sepsisinduced multiple organ failure through intestinal barrier dysfunction,bacterial translocation and ileus.In this review we address the role of the gastrointestinal tract,the mediators,cell types and transduction pathways involved,based on experimental data obtained from models of inflammation-induced ileus and (preliminary) clinical data.The complex interplay within the gastrointestinal wall between mast cells,residential macrophages and glial cells on the one hand,and neurons and smooth muscle cells on the other hand,involves intracellular signaling pathways,Toll-like receptors and a plethora of neuroactive substances such as nitric oxide,prostaglandins,cytokines,chemokines,growth factors,tryptases and hormones.Multidirectional signaling between the different components in the gastrointestinal wall,the spinal cord and central nervous system impacts inflammation and its consequences.We propose that novel therapeutic strategies should target inflammation on the one hand and gastrointestinal motility,gas-trointestinal sensitivity and even pain signaling on the other hand,for instance by impeding afferent neuronal signaling,by activation of the vagal anti-inflammatory pathway or by the use of pharmacological agents such as ghrelin and ghrelin agonists or drugs interfering with the endocannabinoid system. | Benedicte Y De Winter Joris G De Man | 2010 | World Journal of Gastroenterology2010，16，44： | 23 |
| 3 | Structural and functional damage to the hippocampal neurovascular unit in diabetes-related depression显示文摘Previous studies have shown that models of depression exhibit structural and functional changes to the neurovascular unit. Thus, we hypothesized that diabetes-related depression might be associated with damage to the hippocampal neurovascular unit. To test this hypothesis, neurons, astrocytes and endothelial cells were isolated from the brain tissues of rat embryos and newborn rats. Hippocampal neurovascular unit co-cultures were produced using the Transwell chamber co-culture system. A model of diabetes-related depression was generated by adding 150 mM glucose and 200 μM corticosterone to the culture system and compared with the neuron + astrocyte and astrocyte + endothelial cell co-culture systems. Western blot assay was used to measure levels of structural proteins in the hippocampal neurovascular unit co-culture system. Levels of basic fibroblast growth factor, angiogenic factor 1, glial cell line–derived neurotrophic factor, transforming growth factor β1, leukemia inhibitory factor and 5-hydroxytryptamine in the hippocampal neurovascular unit co-culture system were measured by enzyme-linked immunosorbent assay. Flow cytometry and terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick end labeling staining was used to assess neuronal apoptosis in the hippocampal neurovascular unit. The neurovascular unit triple cell co-culture system had better barrier function and higher levels of structural and secretory proteins than the double cell co-culture systems. In comparison, in the model of diabetes-related depression, the neurovascular unit was damaged with decreased barrier function, poor structural integrity and impaired secretory function. Moreover, neuronal apoptosis was markedly increased, and 5-hydroxytryptamine levels were reduced. These results suggest that diabetes-related depression is associated with structural and functional damage to the neurovascular unit. Our findings provide a foundation for further studies on the pathogenesis of diabetes-related depression. | Jian Liu Yu-Hong Wang Wei Li Lin Liu Hui Yang Pan Meng Yuan-Shan Han | 2019 | Neural Regeneration Research2019，14，2： | 20 |
| 4 | Roles of neural stem cells in the repair of peripheral nerve injury显示文摘Currently, researchers are using neural stem cell transplantation to promote regeneration after peripheral nerve injury, as neural stem cells play an important role in peripheral nerve injury repair. This article reviews recent research progress of the role of neural stem cells in the repair of peripheral nerve injury. Neural stem cells can not only differentiate into neurons, astrocytes and oligodendrocytes, but can also differentiate into Schwann-like cells, which promote neurite outgrowth around the injury. Transplanted neural stem cells can differentiate into motor neurons that innervate muscles and promote the recovery of neurological function. To promote the repair of peripheral nerve injury, neural stem cells secrete various neurotrophic factors, including brain-derived neurotrophic factor, fibroblast growth factor, nerve growth factor, insulin-like growth factor and hepatocyte growth factor. In addition, neural stem cells also promote regeneration of the axonal myelin sheath, angiogenesis, and immune regulation. It can be concluded that neural stem cells promote the repair of peripheral nerve injury through a variety of ways. | Chong Wang Chang-feng Lu Jiang Peng Cheng-dong Hu Yu Wang | 2017 | Neural Regeneration Research2017，12，12： | 20 |
| 5 | Exosomes as mediators of neuron-glia communication in neuroinflammation显示文摘In recent years,a type of extracellular vesicles named exosomes has emerged that play an important role in intercellular communication under physiological and pathological conditions.These nanovesicles (30–150 nm) contain proteins,RNAs and lipids,and their internalization by bystander cells could alter their normal functions.This review focuses on recent knowledge about exosomes as messengers of neuron-glia communication and their participation in the physiological and pathological functions in the central nervous system.Special emphasis is placed on the role of exosomes under toxic or pathological stimuli within the brain,in which the glial exosomes containing inflammatory molecules are able to communicate with neurons and contribute to the pathogenesis of neuroinflammation and neurodegenerative disorders.Given the small size and characteristics of exosomes,they can cross the blood-brain barrier and be used as biomarkers and diagnosis for brain disorders and neuropathologies.Finally,although the application potential of exosome is still limited,current studies indicate that exosomes represent a promising strategy to gain pathogenic information to identify therapeutically targets and biomarkers for neurological disorders and neuroinflammation. | María Pascual Francesc Ibánez Consuelo Guerri | 2020 | Neural Regeneration Research2020，15，5： | 14 |
| 6 | Nerve growth factor pretreatment against glutamate-induced hippocampal neuronal injury Action mechanism of phosphatase and tensin homologue deleted on chromosome 10显示文摘BACKGROUND: Nerve growth factor (NGF) attenuates glutamate-induced injury to hippocampal neurons, and the human tumor suppressor gene phosphatase and tensin homologue deleted on chromosome 10 (PTEN) promotes neuronal apoptosis. However, effects of PTEN in NGF-mediated neuroprotection against glutamate excitotoxicity remain poorly understood. OBJECTIVE: To investigate the relationship between NGF inhibition of glutamate-induced injury and PTEN. DESIGN, TIME AND SETTING: The randomized, controlled, in vitro study was performed at the Department of Pathophysiology, Medical School of Nantong University, China from October 2007 to March 2008. MATERIALS: Glutamate, NGF, 4, 6-diamidino-2-phenyl-indolediacetate, 3-[4, 5-dimethylthiazol-2-yl]- 2, 5-diphenyl tetrazoliumbromide (MTT), and lactate dehydrogenase kit (Sigma, USA), fluorescence microscope and inverted phase contrast microscope (Olympus, Japan) were used in this study. METHODS: Hippocampal neurons were obtained from newborn (< 24 hours) Sprague Dawley rats and cultured for 7 days. The control group was not treated with any intervention factor, the glutamate group was treated with glutamate (0.2 mmol/L), and NGF groups were treated with NGF (10, 50, 100, and 200 μg/L, respectively) prior to glutamate treatment. MAIN OUTCOME MEASURES: The MTT and lactate dehydrogenase assays were applied to evaluate viability of hippocampal neurons. Morphological changes in hippocampal neurons were observed using an inverted phase-contrast microscope, and neuronal apoptosis was detected by 4, 6-diamidino-2-phenyl-indolediacetate staining. PTEN mRNA and protein expression were measured by reverse transcription-polymerase chain reaction and Western blot analysis, respectively. RESULTS: Glutamate (0.2 mmol/L) induced significantly decreased neuronal viability and greater lactate dehydrogenase efflux compared with the control group (P < 0.01). However, compared with the glutamate group, cell viability significantly increased and lactate dehydrogenase efflux decreased in the NGF group with increasing NGF concentrations (P < 0.05 or P < 0.01). The apoptotic ratio and PTEN mRNA and protein expression decreased in the NGF group compared with the glutamate group (P < 0.01). CONCLUSION: Pretreatment with NGF exerted neuroprotective effects against glutamate-induced injury, partially through inhibition of PTEN expression and neuronal apoptosis. | Yae Hu Jiahui Mao Yan Zhu Ailing Zhou | 2010 | Neural Regeneration Research2010，5，1： | 12 |
| 7 | Diabetes-related alterations in the enteric nervous system and its microenvironment显示文摘Gastric intestinal symptoms common among diabetic patients are often caused by intestinal motility abnormalities related to enteric neuropathy. It has recently been demonstrated that the nitrergic subpopulation of myenteric neurons are especially susceptible to the development of diabetic neuropathy. Additionally, different susceptibility of nitrergic neurons located in different intestinal segments to diabetic damage and their different levels of responsiveness to insulin treatment have been revealed. These findings indicate the importance of the neuronal microenvironment in the pathogenesis of diabetic nitrergic neuropathy. The main focus of this review therefore was to summarize recent advances related to the diabetes-related selective nitrergic neuropathy and associated motility disturbances. Special attention was given to the findings on capillary endothelium and enteric glial cells. Growing evidence indicates that capillary endothelium adjacent to the myenteric ganglia and enteric glial cells surrounding them are determinative in establishing the ganglionic microenvironment. Additionally, recent advances in the development of new strategies to improve glycemic control in type 1 and type 2 diabetes mellitus are also considered in this review. Finally, looking to the future, the recent and promising results of metagenomics for the characterization of the gut microbiome in health and disease such as diabetes are highlighted. | Mária Bagyánszki Nikolett Bódi | 2012 | World Journal of Diabetes2012，3，5： | 11 |
| 8 | Neuroprotective mechanism of Kai Xin San: upregulation of hippocampal insulin-degrading enzyme protein expression and acceleration of amyloid-beta degradation显示文摘Kai Xin San is a Chinese herbal formula composed of Radix Ginseng, Poria, Radix Polygalae and Acorus Tatarinowii Rhizome. It has been used in China for many years for treating amnesia. Kai Xin San ameliorates amyloid-β(Aβ)-induced cognitive dysfunction and is neuroprotective in vivo, but its precise mechanism remains unclear. Expression of insulin-degrading enzyme(IDE), which degrades Aβ, is strongly correlated with cognitive function. Here, we injected rats with exogenous Aβ42(200 μM, 5 μL) into the hippocampus and subsequently administered Kai Xin San(0.54 or 1.08 g/kg/d) intragastrically for 21 consecutive days. Hematoxylin-eosin and Nissl staining revealed that Kai Xin San protected neurons against Aβ-induced damage. Furthermore, enzyme-linked immunosorbent assay, western blot and polymerase chain reaction results showed that Kai Xin San decreased Aβ42 protein levels and increased expression of IDE protein, but not m RNA, in the hippocampus. Our findings reveal that Kai Xin San facilitates hippocampal Aβ degradation and increases IDE expression, which leads, at least in part, to the alleviation of hippocampal neuron injury in rats. | Na Wang Yong-ming Jia Bo Zhang Di Xue Maharjan Reeju Yan Li Shu-ming Huang Xue-wei Liu | 2017 | Neural Regeneration Research2017，12，4： | 11 |
| 9 | Inhibiting endogenous tissue plasminogen activator enhanced neuronal apoptosis and axonal injury after traumatic brain injury显示文摘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. | Jun-Jie Zhao Zun-Wei Liu Bo Wang Ting-Qin Huang Dan Guo Yong-Lin Zhao Jin-Ning Song | 2020 | Neural Regeneration Research2020，15，4： | 10 |
| 10 | Migration of bone marrow progenitor cells in the adult brain of rats and rabbits显示文摘Neurogenesis takes place in the adult mammalian brain in three areas:Subgranular zone of the dentate gyrus(DG);subventricular zone of the lateral ventricle;olfactory bulb.Different molecular markers can be used to characterizethe cells involved in adult neurogenesis.It has been recently suggested that a population of bone marrow(BM)progenitor cells may migrate to the brain and differentiate into neuronal lineage.To explore this hypothesis,we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells.Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells,then after several months in mature neurons and microglial cells,and thus without central nervous system(CNS)lesion.Most of transgene-expressing cells expressed NeuN,a marker of mature neurons.Thus,BM-derived cells may function as progenitors of CNS cells in adult animals.The mechanism by which the cells from the BM come to be neurons remains to be determined.Although the observed gradual increase in transgene-expressing neurons over 16mo suggests that the pathway involved differentiation of BM-resident cells into neurons,cell fusion as the principal route cannot be totally ruled out.Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons.Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector.In addition to cells expressing markers of mature neurons,transgene-positive cells were also positive for nestin and doublecortin,molecules expressed by developing neuronal cells.These cells were actively proliferating,as shown by short term BrdU incorporation studies.Inducing seizures by using kainic acid increased the number of BM progenitor cells transduced by SV40vectors migrating to the hippocampus,and these cells were seen at earlier time points in the DG.We show that the cell membrane chemokine receptor,CCR5,and its ligands,enhance CNS inflammation and seizure activity in a model of neuronal excitotoxicity.SV40-based gene delivery of RNAi targeting CCR5 to the BM results in downregulating CCR5 in circulating cells,suggesting that CCR5 plays an important role in regulating traffic of BM-derived cells into the CNS,both in the basal state and in response to injury.Furthermore,reduction in CCR5 expression incirculating cells provides profound neuroprotection from excitotoxic neuronal injury,reduces neuroinflammation,and increases neuronal regeneration following this type of insult.These results suggest that BM-derived,transgeneexpressing,cells can migrate to the brain and that they become neurons,at least in part,by differentiating into neuron precursors and subsequently developing into mature neurons. | Donnahue Dennie Jean-Pierre Louboutin David S Strayer | 2016 | World Journal of Stem Cells2016，8，4： | 9 |
| 11 | Neuroprotective effect of deferoxamine on erastin-induced ferroptosis in primary cortical neurons显示文摘The iron chelator deferoxamine has been shown to inhibit ferroptosis in spinal cord injury.However,it is unclear whether deferoxamine directly protects neurons from ferroptotic cell death.By comparing the survival rate and morphology of primary neurons and SH-SY5Y cells exposed to erastin,it was found that these cell types respond differentially to the duration and concentration of erastin treatment.Therefore,we studied the mechanisms of ferroptosis using primary cortical neurons from E16 mouse embryos.After treatment with 50μM erastin for 48 hours,reactive oxygen species levels increased,and the expression of the cystine/glutamate antiporter system light chain and glutathione peroxidase 4 decreased.Pretreatment with deferoxamine for 12 hours inhibited these changes,reduced cell death,and ameliorated cellular morphology.Pretreatment with the apoptosis inhibitor Z-DEVD-FMK or the necroptosis inhibitor necrostain-1 for 12 hours did not protect against erastin-induced ferroptosis.Only deferoxamine protected the primary cortical neurons from ferroptosis induced by erastin,confirming the specificity of the in vitro ferroptosis model.This study was approved by the Animal Ethics Committee at the Institute of Radiation Medicine of the Chinese Academy of Medical Sciences,China(approval No.DWLL-20180913)on September 13,2018. | Yan Zhang Bao-You Fan Yi-Lin Pang Wen-Yuan Shen Xu Wang Chen-Xi Zhao Wen-Xiang Li Chang Liu Xiao-Hong Kong Guang-Zhi Ning Shi-Qing Feng Xue Yao | 2020 | Neural Regeneration Research2020，15，8： | 9 |
| 12 | Neural differentiation from embryonic stem cells in vitro : An overview of the signaling pathways显示文摘Neurons derived from embryonic stem cells(ESCs) have gained great merit in both basic research and regenerative medicine. Here we review and summarize the signaling pathways that have been reported to be involved in the neuronal differentiation of ESCs,particularly those associated with in vitro differentiation. The inducers and pathways explored include retinoic acid, Wnt/b-catenin, transforming growth factor/bone morphogenetic protein, Notch, fibroblast growth factor, cytokine, Hedgehog, c-Jun N-terminal kinase/mitogen-activated protein kinase and others. Some other miscellaneous molecular factors that have been reported in the literature are also summarized and discussed. These include calcium, calcium receptor, calcineurin, estrogen receptor, Hox protein, ceramide, glycosaminioglycan, ginsenoside Rg1, opioids, two pore channel 2, nitric oxide, chemically defined medium, cellcell interactions, and physical stimuli. The interaction or crosstalk between these signaling pathways and factors will be explored. Elucidating these signals in detail should make a significant contribution to future progress in stem cell biology and allow, for example, better comparisons to be made between differentiation in vivo and in vitro. Of equal importance, a comprehensive understanding of the pathways that are involved in the development of neurons from ESCs in vitro will also accelerate their application as part of translational medicine. | Jen-Hua Chuang Li-Chu Tung Yenshou Lin | 2015 | World Journal of Stem Cells2015，7，2： | 9 |
| 13 | Cellular and molecular basis of chronic constipation: Taking the functional/idiopathic label out显示文摘In recent years, the improvement of technology and the increase in knowledge have shifted several strongly held paradigms. This is particularly true in gastroenterology, and specifically in the field of the so-called 'functional' or 'idiopathic' disease, where conditions thought for decades to be based mainly on alterations of visceral perception or aberrant psychosomatic mechanisms have, in fact, be reconducted to an organic basis (or, at the very least, have shown one or more demonstrable abnormalities). This is particularly true, for instance, for irritable bowel syndrome, the prototype entity of 'functional' gastrointestinal disorders, where low-grade inflammation of both mucosa and myenteric plexus has been repeatedly demonstrated. Thus, researchers have also investigated other functional/idiopathic gastrointestinal disorders, and found that some organic ground is present, such as abnormal neurotransmission and myenteric plexitis in esophageal achalasia and mucosal immune activation and mild eosinophilia in functional dyspepsia. Here we show evidence, based on our own and other authors' work, that chronic constipation has several abnormalities reconductable to alterations in the enteric nervous system, abnormalities mainly characterized by a constant decrease of enteric glial cells and interstitial cells of Cajal (and, sometimes, of enteric neurons). Thus, we feel that (at least some forms of) chronic constipation should no more be considered as a functional/idiopathic gastrointestinal disorder, but instead as a true enteric neuropathic abnormality. | Gabrio Bassotti Vincenzo Villanacci Dragos Cretoiu Sanda Maria Cretoiu Gabriel Becheanu | 2013 | World Journal of Gastroenterology2013，19，26： | 9 |
| 14 | Propofol decreases the excitability of cholinergic neurons in mouse basal forebrain via GABAa receptors显示文摘Propofol is an intravenous anesthetic that can active y-aminobutyric acid A (GABAa) receptors and generate sedative-hypnotic effects. Propofol has been widely applied clinically to achieve sedation comparable to sleep in humans. The basal forebrain (BF) is a brain region that plays an important role in sleep-wake regulation. Previous studies suggest that propofol affects the sleep-wake circuit via the BF;however, the mechanism remains elusive. In the current study we investigated the effects of propofol on the inherent properties of cholinergic neurons and their ability to convert excitatory inputs into spikes in mouse BF slices using wholecell patch clamp recordings. Bath application of propofol (10μM) significantly elevated the threshold potentials (Vts), decreased the number of spikes in response to a depolarizing current injection, and augmented the inter-spike intervals (ISIs), energy barrier (Vts- Vrs), and absolute refractory periods (ARPs). These effects were eliminated by co-application of a GABAa receptor antagonist picrotoxin (50μM). Altogether, our results reveal that propofol decreases the excitability of cholinergic neurons in mouse BF via GABAa receptors. | Lei Chen Zhi-lai Yang Juan Cheng Ping-ping Zhang Le-sha Zhang Xue-sheng Liu Lie-cheng Wang | 2019 | Acta Pharmacologica Sinica2019，40，6： | 7 |
| 15 | Effects of primary microglia and astrocytes on neural stem cells in in vitro and in vivo models of ischemic stroke显示文摘Transplantation of neural stem cells(NSCs) can protect neurons in animal stroke models;however, their low rates of survival and neuronal differentiation limit their clinical application. Glial niches, an important location of neural stem cells, regulate survival, proliferation and differentiation of neural stem cells. However, the effects of activated glial cells on neural stem cells remain unclear. In the present study, we explored the effects of activated astrocytes and microglia on neural stem cells in vitro stroke models. We also investigated the effects of combined transplantation of neural stem cells and glial cells after stroke in rats. In a Transwell co-culture system, primary cultured astrocytes, microglia or mixed glial cells were exposed to glutamate or H_2O_2 and then seeded in the upper inserts, while primary neural stem cells were seeded in the lower uncoated wells and cultured for 7 days. Our results showed that microglia were conducive to neurosphere formation and had no effects on apoptosis within neurospheres, while astrocytes and mixed glial cells were conducive to neurosphere differentiation and reduced apoptosis within neurospheres, regardless of their pretreatment. In contrast, microglia and astrocytes induced neuronal differentiation of neural stem cells in differentiation medium, regardless of their pretreatment, with an exception of astrocytes pretreated with H_2O_2. Rat models of ischemic stroke were established by occlusion of the middle cerebral artery. Three days later, 5 × 10~5 neural stem cells with microglia or astrocytes were injected into the right lateral ventricle. Neural stem cell/astrocyte-treated rats displayed better improvement of neurological deficits than neural stem cell only-treated rats at 4 days after cell transplantation. Moreover, neural stem cell/microglia-, and neural stem cell/astrocyte-treated rats showed a significant decrease in ischemic volume compared with neural stem celltreated rats. These findings indicate that microglia and astrocytes exert different effects on neural stem cells, and that co-transplantation of neural stem cells and astrocytes is more conducive to the recovery of neurological impairment in rats with ischemic stroke. The study was approved by the Animal Ethics Committee of Tongji University School of Medicine, China(approval No. 2010-TJAA08220401) in 2010. | Sheng-Jun Wen Xi-Min Zheng Li-Fen Liu Na-Na Li Hai-An Mao Liang Huang Qiong-Lan Yuan | 2021 | Neural Regeneration Research2021，16，9： | 7 |
| 16 | Real-time Microwave Exposure Induces Calcium Efflux in Primary Hippocampal Neurons and Primary Cardiomyocytes显示文摘Objective To detect the effects of microwave on calcium levels in primary hippocampal neurons and primary cardiomyocytes by the real-time microwave exposure combined with laser scanning confocal microscopy. Methods The primary hippocampal neurons and primary cardiomyocytes were cultured and labeled with probes, including Fluo-4 AM, Mag-Fluo-AM, and Rhod-2, to reflect the levels of whole calcium [Ca^(2+)], endoplasmic reticulum calcium [Ca^(2+)]ER, and mitochondrial calcium [Ca^(2+)]MIT, respectively. Then, the cells were exposed to a pulsed microwave of 2.856 GHz with specific absorption rate(SAR) values of 0, 4, and 40 W/kg for 6 min to observe the changes in calcium levels. Results The results showed that the 4 and 40 W/kg microwave radiation caused a significant decrease in the levels of [Ca^(2+)], [Ca^(2+)]ER, and [Ca^(2+)]MIT in primary hippocampal neurons. In the primary cardiomyocytes, only the 40 W/kg microwave radiation caused the decrease in the levels of [Ca^(2+)], [Ca^(2+)]ER, and [Ca^(2+)]MIT. Primary hippocampal neurons were more sensitive to microwave exposure than primary cardiomyocytes. The mitochondria were more sensitive to microwave exposure than the endoplasmic reticulum. Conclusion The calcium efflux was occurred during microwave exposure in primary hippocampal neurons and primary cardiomyocytes. Additionally, neurons and mitochondria were sensitive cells and organelle respectively. | WANG Hui ZHANG Jing HU Shao Hua TAN Sheng Zhi ZHANG Bo ZHOU Hong Mei PENG Rui Yun | 2018 | Biomedical and Environmental Sciences2018，31，8： | 7 |
| 17 | Cytoprotective Mechanism of the Novel Gastric Peptide BPC157 in Gastrointestinal Tract and Cultured Enteric Neurons and Glial Cells显示文摘Dear Editor,Body protection compound (BPC) 157 is a stable gastric pentadecapeptide. Predrag Sikiric’s team has carried out many investigations of its cytoprotective effects in different organs and tissues (1, 2)Their evidence indicates that BPC157 has potent cytoprotection in neural injury and gastrointestinal (GI) ulcers. Nevertheless. | Xi-Yu Wang Meihua Qu Rui Duan Dengping Shi Ling Jin Jinping Gao Jackie D.Wood Junhua Li Guo-Du Wang | 2019 | Neuroscience Bulletin2019，35，1： | 6 |
| 18 | Material basis for inhibition of Dragon's Blood on evoked discharges of wide dynamic range neurons in spinal dorsal horn of rats显示文摘In vivo experiments were designed to verify the analgesic effect of Dragon’s Blood and the material basis for this effect. Extracellular microelectrode recordings were used to observe the effects of Dragon’s Blood and various combinations of the three components (cochinchinenin A, cochinchinenin B, and loureirin B) extracted from Dragon’s Blood on the discharge activities of wide dynamic range (WDR) neurons in spinal dorsal horn (SDH) of intact male Wistar rats evoked by electric stimulation at sciatic nerve. When the Hill's coefficients describing the dose-response relations of drugs were dif-ferent, based on the concept of dose equivalence, the equations of additivity surfaces which can be applied to assess the interaction between three drugs were derived. Adopting the equations and Tal-larida's isobole equations used to assess the interaction between two drugs with dissimilar dose-response relations, the effects produced by various combinations of the three components in modulating the evoked discharge activities of WDR neurons were evaluated. Results showed that Dragon’s Blood and its three components could inhibit the evoked discharge frequencies of WDR neurons in a concentration-dependent way. The Hill's coefficients describing dose-response relations of three components were different. Only the combined effect of cochinchinenin A, cochinchinenin B and loureirin B was similar to that of Dragons Blood. Furthermore, the combined effect was synergistic. This investigation demonstrated that through the synergistic interaction of the three components Dragon’s Blood could interfere with the transmission and processing of pain signals in spinal dorsal horn. All these further proved that the combination of cochinchinenin A, cochinchinenin B, and loureirin B was the material basis for the analgesic effect of Dragon’s Blood. | GUO Min, CHEN Su & LIU XiangMing Department of Biological & Medical Engineering, South-Central University for Nationalities, Wuhan 430074, China | 2008 | Science China(Life Sciences)2008，51，11： | 6 |
| 19 | Effect of lentiviral vector-mediated overexpression of hypoxia-inducible factor 1 alpha delivered by pluronic F-127 hydrogel on brachial plexus avulsion in rats显示文摘Brachial plexus avulsion often results in massive motor neuron death and severe functional deficits of target muscles. However, no satisfactory treatment is currently available. Hypoxia-inducible factor 1α is a critical molecule targeting several genes associated with ischemia-hypoxia damage and angiogenesis. In this study, a rat model of brachial plexus avulsion-reimplantation was established, in which C5–7 ventral nerve roots were avulsed and only the C6 root reimplanted. Different implants were immediately injected using a microsyringe into the avulsion-reimplantation site of the C6 root post-brachial plexus avulsion. Rats were randomly divided into five groups: phosphate-buffered saline, negative control of lentivirus, hypoxia-inducible factor 1α(hypoxia-inducible factor 1α overexpression lentivirus), gel(pluronic F-127 hydrogel), and gel + hypoxia-inducible factor 1α(pluronic F-127 hydrogel + hypoxia-inducible factor 1α overexpression lentivirus). The Terzis grooming test was performed to assess recovery of motor function. Scores were higher in the hypoxia-inducible factor 1α and gel +hypoxia-inducible factor 1α groups(in particular the gel + hypoxia-inducible factor 1α group) compared with the phosphate-buffered saline group. Electrophysiology, fluorogold retrograde tracing, and immunofluorescent staining were further performed to investigate neural pathway reconstruction and changes of neurons, motor endplates, and angiogenesis. Compared with the phosphate-buffered saline group, action potential latency of musculocutaneous nerves was markedly shortened in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor1α groups. Meanwhile, the number of fluorogold-positive cells and ChAT-positive neurons, neovascular area(labeled by CD31 around av ulsed sites in ipsilateral spinal cord segments), and the number of motor endplates in biceps brachii(identified by α-bungarotoxin) were all visibly increased, as well as the morphology of motor endplate in biceps brachil was clear in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor 1α groups. Taken together, delivery of hypoxia-inducible factor 1α overexpression lentiviral vectors mediated by pluronic F-127 effectively promotes spinal root regeneration and functional recovery post-brachial plexus avulsion. All animal procedures were approved by the Institutional Animal Care and Use Committee of Guangdong Medical University, China. | Tao Wang Li-Ni Zeng Zhe Zhu Yu-Hui Wang Lu Ding Wei-Bin Luo Xiao-Min Zhang Zhi-Wei He Hong-Fu Wu | 2019 | Neural Regeneration Research2019，14，6： | 5 |
| 20 | Stem cell therapy for Parkinson’s disease: safety and modeling显示文摘For decades,clinicians have developed medications and therapies to alleviate the symptoms of Parkinson’s disease,but no treatment currently can slow or even stop the progression of this localized neurodegeneration.Fortunately,sparked by the genetic revolution,stem cell reprogramming research and the advancing capabilities of personalization in medicine enable forward-thinking to unprecedented patient-specific modeling and cell therapies for Parkinson’s disease using induced pluripotent stem cells(iPSCs).In addition to modeling Parkinson’s disease more accurately than chemically-induced animal models,patient-specific stem cell lines can be created,elucidating the effects of genetic susceptibility and sub-populations’differing responses to in vitro treatments.Sourcing cell therapy with iPSC lines provides ethical advantages because these stem cell lines do not require the sacrifice of human zygotes and genetically-specific drug trails can be tested in vitro without lasting damage to patients.In hopes of finally slowing the progression of Parkinson’s disease or re-establishing function,iPSC lines can ultimately be corrected with gene therapy and used as cell sources for neural transplantation for Parkinson’s disease.With relatively localized neural degeneration,similar to spinal column injury,Parkinson’s disease presents a better candidacy for cell therapy when compared to other diffuse degeneration found in Alzheimer’s or Huntington’s Disease.Neurosurgical implantation of pluripotent cells poses the risk of an innate immune response and tumorigenesis.Precautions,therefore,must be taken to ensure cell line quality before transplantation.While cell quality can be quantified using a number of assays,a yielding a high percentage of therapeutically relevant dopaminergic neurons,minimal de novo genetic mutations,and standard chromosomal structure is of the utmost importance.Current techniques focus on iPSCs because they can be matched with donors using human leukocyte antigens,thereby reducing the severity and risk of immune rejection.In August of 2018,researchers in Kyoto,Japan embarked on the first human clinical trial using iPSC cell therapy transplantation for patients with moderate Parkinson’s disease.Transplantation of many cell sources has already proven to reduce Parkinson’s disease symptoms in mouse and primate models.Here we discuss the history and implications for cell therapy for Parkinson’s disease,as well as the necessary safety standards needed for using iPSC transplantation to slow or halt the progression of Parkinson’s disease. | Theo Stoddard-Bennett Renee Reijo Pera | 2020 | Neural Regeneration Research2020，15，1： | 5 |
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