Neovascularization and angiogenesis in the brain are important physiological processes for normal brain development and repair/regeneration following insults. Integrins are cell surface adhesion receptors mediating im...Neovascularization and angiogenesis in the brain are important physiological processes for normal brain development and repair/regeneration following insults. Integrins are cell surface adhesion receptors mediating important function of cells such as survival, growth and development during tissue organization, differentiation and organogenesis. In this study, we used an integrin-binding array platform to identify the important types of integrins and their binding peptides that facilitate adhesion, growth, development, and vascular-like network formation of rat primary brain microvascular endothelial cells. Brain microvascular endothelial cells were isolated from rat brain on post-natal day 7. Cells were cultured in a custom-designed integrin array system containing short synthetic peptides binding to 16 types of integrins commonly expressed on cells in vertebrates. After 7 days of culture, the brain microvascular endothelial cells were processed for immunostaining with markers for endothelial cells including von Willibrand factor and platelet endothelial cell adhesion molecule. 5-Bromo-2′-dexoyuridine was added to the culture at 48 hours prior to fixation to assess cell proliferation. Among 16 integrins tested, we found that α5β1, αvβ5 and αvβ8 greatly promoted proliferation of endothelial cells in culture. To investigate the effect of integrin-binding peptides in promoting neovascularization and angiogenesis, the binding peptides to the above three types of integrins were immobilized to our custom-designed hydrogel in three-dimensional(3 D) culture of brain microvascular endothelial cells with the addition of vascular endothelial growth factor. Following a 7-day 3 D culture, the culture was fixed and processed for double labeling of phalloidin with von Willibrand factor or platelet endothelial cell adhesion molecule and assessed under confocal microscopy. In the 3 D culture in hydrogels conjugated with the integrin-binding peptide, brain microvascular endothelial cells formed interconnected vascular-like network with clearly discernable lumens, which is reminiscent of brain microvascular network in vivo. With the novel integrin-binding array system, we identified the specific types of integrins on brain microvascular endothelial cells that mediate cell adhesion and growth followed by functionalizing a 3 D hydrogel culture system using the binding peptides that specifically bind to the identified integrins, leading to robust growth and lumenized microvascular-like network formation of brain microvascular endothelial cells in 3 D culture. This technology can be used for in vitro and in vivo vascularization of transplants or brain lesions to promote brain tissue regeneration following neurological insults.展开更多
Objective:The integration of training in theory and practice across the medical education spectrum is being encouraged to increase student understanding and skills in the sciences.This study aimed to determine the dec...Objective:The integration of training in theory and practice across the medical education spectrum is being encouraged to increase student understanding and skills in the sciences.This study aimed to determine the deciding factors that drive students'perceived advantages in class to improve precision education and the teaching model.Methods:A mixed strategy of an existing flipped classroom(FC)and a case-based learning(CBL)model was conducted in a medical morphology curriculum for 575 postgraduate students.The subjective learning evaluation of the individuals(learning time,engagement,study interest and concentration,and professional integration)was collected and analyzed after FC-CBL model learning.Results:The results from the general evaluation showed promising results of the medical morphology in the FC-CBL model.Students felt more engaged by instructors in person and benefited in terms of time-saving,flexible arrangements,and professional improvement.Our study contributed to the FC-CBL model in Research Design in postgraduate training in 4 categories:1)advancing a guideline of precision teaching according to individual characteristics;2)revealing whether a learning background is needed for a Research Design course to guide setting up a preliminary course;3)understanding the perceived advantages and their interfaces;and 4)barriers and/or improvement to implement the FC-CBL model in the Research Design class,such as a richer description of e-learning and hands-on practice.Conclusion:Undertaking a FC-CBL combined model could be a useful addition to pedagogy for medical morphology learning in postgraduate training.展开更多
Epilepsy is a neurological disorder characterized by high morbidity,high recurrence,and drug resistance.Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy.Meta...Epilepsy is a neurological disorder characterized by high morbidity,high recurrence,and drug resistance.Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy.Metabotropic glutamate receptors(mGluRs)are G protein-coupled receptors activated by glutamate and are key regulators of neuronal and synaptic plasticity.Dysregulated mGluR signaling has been associated with various neurological disorders,and numerous studies have shown a close relationship between mGluRs expression/activity and the development of epilepsy.In this review,we first introduce the three groups of mGluRs and their associated signaling pathways.Then,we detail how these receptors influence epilepsy by describing the signaling cascades triggered by their activation and their neuroprotective or detrimental roles in epileptogenesis.In addition,strategies for pharmacological manipulation of these receptors during the treatment of epilepsy in experimental studies is also summarized.We hope that this review will provide a foundation for future studies on the development of mGluR-targeted antiepileptic drugs.展开更多
Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019)...Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019).Although the only FDA-approved effective medication is tissue plasminogen activator(tPA),it should be administrated within 4.5 hours of ischemic stroke.Furthermore,tPA has been an integral part of managing acute ischemic stro ke.展开更多
In this editorial,we offer our perspective on the groundbreaking study entitled“Hypoxia and inflammatory factor preconditioning enhances the immunosup-pressive properties of human umbilical cord mesenchymal stem cell...In this editorial,we offer our perspective on the groundbreaking study entitled“Hypoxia and inflammatory factor preconditioning enhances the immunosup-pressive properties of human umbilical cord mesenchymal stem cells”,recently published in World Journal of Stem Cells.Despite over three decades of research on the clinical application of mesenchymal stem cells(MSCs),only a few therapeutic products have made it to clinical use,due to multiple preclinical and clinical challenges yet to be addressed.The study proved the hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics,which revealed the combination of inflammatory factors and hypoxic preconditioning offers a promising approach to enhance the function of MSCs.As we delve deeper into the intricacies of pretreat-ment methodologies,we anticipate a transformative shift in the landscape of MSC-based therapies,ultimately contributing to improved patient outcomes and advancing the field as a whole.展开更多
The efficacy of electroacupuncture in the treatment of peripheral facial paralysis is known, but the specific mechanism has not been clarified. Glial cell-derived neurotrophic factor(GDNF) has been shown to protect ne...The efficacy of electroacupuncture in the treatment of peripheral facial paralysis is known, but the specific mechanism has not been clarified. Glial cell-derived neurotrophic factor(GDNF) has been shown to protect neurons by binding to N-cadherin. Our previous results have shown that electroacupuncture could increase the expression of N-cadherin mRNA in facial neurons and promote facial nerve regeneration. In this study, the potential mechanisms by which electroacupuncture promotes nerve regeneration were elucidated through assessing the effects of electroacupuncture on GDNF and N-cadherin expression in facial motoneurons of rabbits with peripheral facial nerve crush injury. New Zealand rabbits were randomly divided into a normal group(normal control, n = 21), injury group(n = 45) and electroacupuncture group(n = 45). Model rabbits underwent facial nerve crush injury only. Rabbits in the electroacupuncture group received facial nerve injury, and then underwent electroacupuncture at Yifeng(TE17), Jiache(ST6), Sibai(ST2), Dicang(ST4), Yangbai(GB14), Quanliao(SI18), and Hegu(LI4; only acupuncture, no electrical stimulation). The results showed that in behavioral assessments, the total scores of blink reflex, vibrissae movement, and position of apex nasi, were markedly lower in the EA group than those in the injury group. Hematoxylin-eosin staining of the right buccinator muscle of each group showed that the cross-sectional area of buccinator was larger in the electroacupuncture group than in the injury group on days 1, 14 and 21 post-surgery. Toluidine blue staining of the right facial nerve tissue of each group revealed that on day 14 post-surgery, there was less axonal demyelination and fewer inflammatory cells in the electroacupuncture group compared with the injury group. Quantitative real time-polymerase chain reaction showed that compared with the injury group, N-cadherin mRNA levels on days 4, 7, 14 and 21 and GDNF mRNA levels on days 4, 7 and 14 were significantly higher in the electroacupuncture group. Western blot assay displayed that compared with the injury group, the expression of GDNF protein levels on days 7, 14 and 21 were significantly upregulated in the electroacupuncture group. The histology with hematoxylin-eosin staining and Nissl staining of brainstem tissues containing facial neurons in the middle and lower part of the pons exhibited that on day 7 post-surgery, there were significantly fewer apoptotic neurons in the electroacupuncture group than in the injury group. By day 21, there was no significantly difference in the number of neurons between the electroacupuncture and normal groups. Taken together, these results have confirmed that electroacupuncture promotes regeneration of peripheral facial nerve injury in rabbits, inhibits neuronal apoptosis, and reduces peripheral inflammatory response, resulting in the recovery of facial muscle function. This is achieved by up-regulating the expression of GDNF and N-cadherin in central facial neurons.展开更多
Nicotiflorin is a flavonoid extracted from Carthamus tinctorius.Previous studies have shown its cerebral protective effect,but the mechanism is undefined.In this study,we aimed to determine whether nicotiflorin protec...Nicotiflorin is a flavonoid extracted from Carthamus tinctorius.Previous studies have shown its cerebral protective effect,but the mechanism is undefined.In this study,we aimed to determine whether nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis through the JAK2/STAT3 pathway.The cerebral ischemia/reperfusion injury model was established by middle cerebral artery occlusion/reperfusion.Nicotiflorin(10 mg/kg) was administered by tail vein injection.Cell apoptosis in the ischemic cerebral cortex was examined by hematoxylin-eosin staining and terminal deoxynucleotidyl transferase d UTP nick end labeling assay.Bcl-2 and Bax expression levels in ischemic cerebral cortex were examined by immunohistochemial staining.Additionally,p-JAK2,p-STAT3,Bcl-2,Bax,and caspase-3 levels in ischemic cerebral cortex were examined by western blot assay.Nicotiflorin altered the shape and structure of injured neurons,decreased the number of apoptotic cells,down-regulates expression of p-JAK2,p-STAT3,caspase-3,and Bax,decreased Bax immunoredactivity,and increased Bcl-2 protein expression and immunoreactivity.These results suggest that nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis via the JAK2/STAT3 pathway.展开更多
Ginsenoside Rb1 has been reported to exert anti-aging and anti-neurodegenerative effects. In the present study, we investigate whether ginsenoside Rb1 is involved in neurite outgrowth and neuroprotection against damag...Ginsenoside Rb1 has been reported to exert anti-aging and anti-neurodegenerative effects. In the present study, we investigate whether ginsenoside Rb1 is involved in neurite outgrowth and neuroprotection against damage induced by amyloid beta(25–35) in cultured hippocampal neurons, and explore the underlying mechanisms. Ginsenoside Rb1 significantly increased neurite outgrowth in hippocampal neurons, and increased the expression of phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2. These effects were abrogated by API-2 and PD98059, inhibitors of the signaling proteins Akt and MEK. Additionally, cultured hippocampal neurons were exposed to amyloid beta(25–35) for 30 minutes; ginsenoside Rb1 prevented apoptosis induced by amyloid beta(25–35), and this effect was blocked by API-2 and PD98059. Furthermore, ginsenoside Rb1 significantly reversed the reduction in phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2 levels induced by amyloid beta(25–35), and API-2 neutralized the effect of ginsenoside Rb1. The present results indicate that ginsenoside Rb1 enhances neurite outgrowth and protects against neurotoxicity induced by amyloid beta(25–35) via a mechanism involving Akt and extracellular signal-regulated kinase 1/2 signaling.展开更多
Long non-coding RNAs(lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury ti...Long non-coding RNAs(lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury tissue from three patients of the 101 st Hospital of the People's Liberation Army, China(specifically, a 36-year-old male, a 52-year-old female, and a 49-year-old female), who were diagnosed with traumatic brain injury and underwent brain contusion removal surgery. Tissue surrounding the brain contusion in the three patients was used as control tissue to observe expression characteristics of lncRNAs and mRNAs in human traumatic brain injury tissue. Volcano plot filtering identified 99 lncRNAs and 63 mRNAs differentially expressed in frontotemporal tissue of the two groups(P < 0.05, fold change > 1.2). Microarray analysis showed that 43 lncRNAs were up-regulated and 56 lncRNAs were down-regulated. Meanwhile, 59 mRNAs were up-regulated and 4 mRNAs were down-regulated. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses revealed 27 signaling pathways associated with target genes and, in particular, legionellosis and influenza A signaling pathways. Subsequently, a lncRNA-gene network was generated, which showed an absolute correlation coefficient value > 0.99 for 12 lncRNA-mRNA pairs. Finally, quantitative real-time polymerase chain reaction confirmed different expression of the five most up-regulated mRNAs within the two groups, which was consistent with the microarray results. In summary, our results show that expression profiles of mRNAs and lncRNAs are significantly different between human traumatic brain injury tissue and surrounding tissue, providing novel insight regarding lncRNAs' involvement in human traumatic brain injury. All participants provided informed consent. This research was registered in the Chinese Clinical Trial Registry(registration number: ChiCTR-TCC-13004002) and the protocol version number is 1.0.展开更多
A Schwann cell has regenerative capabilities and is an important cell in the peripheral nervous system.This microarray study is part of a bioinformatics study that focuses mainly on Schwann cells. Microarray data prov...A Schwann cell has regenerative capabilities and is an important cell in the peripheral nervous system.This microarray study is part of a bioinformatics study that focuses mainly on Schwann cells. Microarray data provide information on differences between microarray-based and experiment-based gene expression analyses. According to microarray data, several genes exhibit increased expression(fold change) but they are weakly expressed in experimental studies(based on morphology, protein and mRNA levels). In contrast, some genes are weakly expressed in microarray data and highly expressed in experimental studies;such genes may represent future target genes in Schwann cell studies. These studies allow us to learn about additional genes that could be used to achieve targeted results from experimental studies. In the current big data study by retrieving more than 5000 scientific articles from PubMed or NCBI, Google Scholar, and Google, 1016(up-and downregulated) genes were determined to be related to Schwann cells. However,no experiment was performed in the laboratory; rather, the present study is part of a big data analysis. Our study will contribute to our understanding of Schwann cell biology by aiding in the identification of genes.Based on a comparative analysis of all microarray data, we conclude that the microarray could be a good tool for predicting the expression and intensity of different genes of interest in actual experiments.展开更多
The principal pathology of Alzheimer's disease includes neuronal extracellular deposition of amyloid-beta peptides and formation of senile pl aques,which in turn induce neuroinflammation in the brain.Triptolide,a ...The principal pathology of Alzheimer's disease includes neuronal extracellular deposition of amyloid-beta peptides and formation of senile pl aques,which in turn induce neuroinflammation in the brain.Triptolide,a natural extract from the vine-like herb Tripterygium wilfordii Hook F,has potent anti-inflammatory and immunosuppressive efficacy.Therefore,we determined if triptolide can inhibit activation and proliferation of microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer's disease.We used 1 or 5 μg/kg/d triptolide to treat APP/PS1 double transgenic mice(aged 4–4.5 months) for 45 days.Unbiased stereology analysis found that triptolide dose-dependently reduced the total number of microglial cells,and transformed microglial cells into the resting state.Further,triptolide(5 μg/kg/d) also reduced the total number of hippocampal astrocytes.Our in vivo test results indicate that triptolide suppresses activation and proliferation of microglial cells and astrocytes in the hippocampus of APP/PS1 double transgenic mice with Alzheimer's disease.展开更多
There are two types of cell death-apoptosis and necrosis. Apoptosis is cell death regulated by cell signaling pathways, while necrosis has until recently been considered a passive mechanism of cell death caused by env...There are two types of cell death-apoptosis and necrosis. Apoptosis is cell death regulated by cell signaling pathways, while necrosis has until recently been considered a passive mechanism of cell death caused by environmental pressures. However, recent studies show that necrosis can also be regulated by specific cell signaling pathways. This mode of death, termed necroptosis, has been found to be related to the occurrence and development of many diseases. We used bibliometrics to analyze the global output of literature on necroptosis in the field of neuroscience published in the period 2007–2019 to identify research hotspots and prospects. We included 145 necroptosisrelated publications and 2239 references published in the Web of Science during 2007–2019. Visualization analysis revealed that the number of publications related to necroptosis has increased year by year, reaching a peak in 2019. China is the country with the largest number of publications. Key word and literature analyses demonstrated that mitochondrial function change, stroke, ischemia/reperfusion and neuroinflammation are likely the research hotspots and future directions of necroptosis research in the nervous system. The relationship between immune response-related factors, damage-associated molecular patterns, pathogen-associated molecular patterns and necroptosis may become a potential research hotspot in the future. Taken together, our findings suggest that although the inherent limitations of bibliometrics may affect the accuracy of the literature-based prediction of research hotspots, the results obtained from the included publications can provide a reference for the study of necroptosis in the field of neuroscience.展开更多
Previous studies have demonstrated that doublecortin-positive immature neurons exist predominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very w...Previous studies have demonstrated that doublecortin-positive immature neurons exist predominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very weak properties of self-proliferation during adulthood under physiological conditions. To verify whether environmental enrichment has an impact on the proliferation and maturation of these immature neurons in the prefrontal cortex of adult guinea pigs, healthy adult guinea pigs were subjected to short-term environmental enrichment. Animals were allowed to play with various cognitive and physical stimulating objects over a period of 2 weeks, twice per day, for 60 minutes each. Immunofluorescence staining results indicated that the number of doublecortin-positive cells in layer II of the prefrontal cortex was significantly increased after short-term environmental enrichment exposure. In addition, these doublecortin-positive cells co-expressed 5-bromo-2-deoxyuridine(a marker of cell proliferation), c-Fos(a marker of cell viability) and NeuN(a marker of mature neurons). Experimental findings showed that short-term environmental enrichment can induce proliferation, activation and maturation of doublecortin-positive cells in layer II of the prefrontal cortex of adult guinea pigs.展开更多
Nestin+ neurons have been shown to express choline acetyltransferase(ChAT) in the medial septum-diagonal band of Broca in adult rats. This study explored the projection of nestin+ neurons to the olfactory bulb and the...Nestin+ neurons have been shown to express choline acetyltransferase(ChAT) in the medial septum-diagonal band of Broca in adult rats. This study explored the projection of nestin+ neurons to the olfactory bulb and the time course of nestin+ neurons in the medial septum-diagonal band of Broca in adult rats during injury recovery after olfactory nerve transection. This study observed that all nestin+ neurons were double-labeled with ChAT in the medial septum-diagonal band of Broca. Approximately 53.6% of nestin+ neurons were projected to the olfactory bulb and co-labeled with fast blue. A large number of nestin+ neurons were not present in each region of the medial septum-diagonal band of Broca. Nestin+ neurons in the medial septum and vertical limb of the diagonal band of Broca showed obvious compensatory function. The number of nestin+ neurons decreased to a minimum later than nestin–/ChAT+ neurons in the medial septum-diagonal band of Broca. The results suggest that nestin+ cholinergic neurons may have a closer connection to olfactory bulb neurons. Nestin+ cholinergic neurons may have a stronger tolerance to injury than Nestin–/ChAT+ neurons. The difference between nestin+ and nestin–/ ChAT+ neurons during the recovery process requires further investigations.展开更多
This study aimed to examine the biocompatibility of calcium titanate(CaTiO_3) coating prepared by a simplified technique in an attempt to assess the potential of CaTiO_3 coating as an alternative to current implant co...This study aimed to examine the biocompatibility of calcium titanate(CaTiO_3) coating prepared by a simplified technique in an attempt to assess the potential of CaTiO_3 coating as an alternative to current implant coating materials. CaTiO_3-coated titanium screws were implanted with hydroxyapatite(HA)-coated or uncoated titanium screws into medial and lateral femoral condyles of 48 New Zealand white rabbits. Imaging, histomorphometric and biomechanical analyses were employed to evaluate the osseointegration and biocompatibility 12 weeks after the implantation. Histology and scanning electron microscopy revealed that bone tissues surrounding the screws coated with CaTiO_3 were fully regenerated and they were also well integrated with the screws. An interfacial fibrous membrane layer, which was found in the HA coating group, was not noticeable between the bone tissues and CaTiO_3-coated screws. X-ray imaging analysis showed in the CaTiO_3 coating group, there was a dense and tight binding between implants and the bone tissues; no radiation translucent zone was found surrounding the implants as well as no detachment of the coating and femoral condyle fracture. In contrast, uncoated screws exhibited a fibrous membrane layer, as evidenced by the detection of a radiation translucent zone between the implants and the bone tissues. Additionally, biomechanical testing revealed that the binding strength of CaTiO_3 coating with bone tissues was significantly higher than that of uncoated titanium screws, and was comparable to that of HA coating. The study demonstrated that CaTiO_3 coating in situ to titanium screws possesses great biocompatibility and osseointegration comparable to HA coating.展开更多
Over the past two decades,many investigators have reported how extracellular matrix molecules act to regulate neuroplasticity.The majority of these studies involve proteins which are targets of matrix metalloproteinas...Over the past two decades,many investigators have reported how extracellular matrix molecules act to regulate neuroplasticity.The majority of these studies involve proteins which are targets of matrix metalloproteinases.Importantly,these enzyme/substrate interactions can regulate degenerative and regenerative phases of synaptic plasticity,directing axonal and dendritic reorganization after brain insult.The present review first summarizes literature support for the prominent role of matrix metalloproteinases during neuroregeneration,followed by a discussion of data contrasting adaptive and maladaptive neuroplasticity that reveals time-dependent metalloproteinase/substrate regulation of postinjury synaptic recovery.The potential for these enzymes to serve as therapeutic targets for enhanced neuroplasticity after brain injury is illustrated with experiments demonstrating that metalloproteinase inhibitors can alter adaptive and maladaptive outcome.Finally,the complexity of metalloproteinase role in reactive synaptogenesis is revealed in new studies showing how these enzymes interact with immune molecules to mediate cellular response in the local regenerative environment,and are regulated by novel binding partners in the brain extracellular matrix.Together,these different examples show the complexity with which metalloproteinases are integrated into the process of neuroregeneration,and point to a promising new angle for future studies exploring how to facilitate brain plasticity.展开更多
Recently, epidemiological studies on the etiology of peripheral neuropathies have revealed that hyperlipidemia is a novel risk factor. Plasma lipid levels were confirmed to be associated with the incidence of many per...Recently, epidemiological studies on the etiology of peripheral neuropathies have revealed that hyperlipidemia is a novel risk factor. Plasma lipid levels were confirmed to be associated with the incidence of many peripheral neuropathies including axonal distal polyneuropathy, vision and hearing loss, motor nerve system lesions and sympathetic nerve system dysfunction. Moreover, different lipid components such as cholesterol, triacylglycerols and lipoprotein are involved in the pathogenesis of these neuropathies. This review aimed to discuss the effect of hyperlipidemia on the peripheral nervous system and its association with peripheral neuropathies. Furthermore, a detailed discussion focusing on the explicit mechanisms related to hyperlipidemia-induced peripheral neuropathies is presented here. These mechanisms, including intracellular oxidative stress, inflammatory lesions, ischemia and dysregulation of local lipid metabolism, share pathways and interact mutually. In addition, we examined current information on clinical trials to prevent and treat peripheral neuropathies caused by hyperlipidemia, with a predictive discussion regarding the orientation of future investigations.展开更多
In this study, a rat model of inflammatory pain was produced by injecting complete Freund's adjuvant into the hind paw, and the expression of acetylated histone 3 in the spinal cord dorsal horn was examined using ...In this study, a rat model of inflammatory pain was produced by injecting complete Freund's adjuvant into the hind paw, and the expression of acetylated histone 3 in the spinal cord dorsal horn was examined using immunohistochemical staining. One day following injection, there was a dramatic decrease in acetylated histone 3 expression in spinal cord dorsal horn neurons. However, on day 7, expression recovered in adjuvant-injected rats. While acetylated histone 3 labeling was present in dorsal horn neurons, it was more abundant in astrocytes and microglial cells. The recovery of acetylated histone 3 expression was associated with a shift in expression of the protein from neurons to glial cells. Morphine injection significantly upregulated the expression of acetylated histone 3 in spinal cord dorsal horn neurons and glial cells 1 day after injection, especially in astrocytes, preventing the transient downregulation. Our results indicate that inflammatory pain induces a transient downregulation of acetylated histone 3 in the spinal cord dorsal horn at an early stage following adjuvant injection, and that this effect can be reversed by morphine. Thus, the downregulation of acetylated histone 3 may be involved in the development of inflammatory pain.展开更多
Objective The purpose of this study is to identify the molecular basis of the contacting -neuron membrane K+ conductance in glia cells of native bovine retina. Methods RT-PCR, Northern blot and Western blot analyses w...Objective The purpose of this study is to identify the molecular basis of the contacting -neuron membrane K+ conductance in glia cells of native bovine retina. Methods RT-PCR, Northern blot and Western blot analyses were used to detect the expression of the inwardly rectifying K+ (Kir) channel subunits Kir2.1 in native bovine RPE and neural retina. The distribution of Kir2.1 protein was determined in frozen sections of bovine retina-RPEchoroid by indirect immunofluorescence analysis. Results RT-PCR analysis reveals Kir2.1 transcript in both RPE and neural retina. In Northern blots, Kir2.1 probe hybridizes to an appropriately sized-transcript in neural retina but not in RPE. In Western blots, Kir2.1 antibody recognizes a major monomer of about 60 kDa in neural retina but not in RPE. Immunofluorescence reveals that Kir2.1 immunostaining is expressed at many parts of Muller cells, especially in the membrane domains of Muller cells that contact retinal neurons, i. e. , along the two stem processes,over the soma, and in the side branches extending into the synaptic layers. No immunostaining is seen in RPE. Doubling staining shows that Kir2.1 proteins and glutamine synthetase proteins which are a marker of Muller cell co-localized well. Conclusions These results reveal that Kir2.1 is localized in the Muller cells, no Kir2.1 in RPE. These data suggests that Kir2.1 may be involved in the transport of K+ in the bovine neural retina.展开更多
A seven-month old female presented with left tibial hemimelia(or congenital tibial aplasia; Weber type VIIb, Jones et al type 1a), seven-toed preaxial polydactyly, and severe club foot(congenital talipes equinovarus)....A seven-month old female presented with left tibial hemimelia(or congenital tibial aplasia; Weber type VIIb, Jones et al type 1a), seven-toed preaxial polydactyly, and severe club foot(congenital talipes equinovarus). Definitive amputation surgery disarticulated the lower limb at the knee. This case report describes the anatomical findings of a systematic post-amputation examination of the lower limb's superficial dissection, X-ray s, and computed to mography (CT) scans. From the X-rays and CT scans, we found curved and overlapping preaxial supernumerary toes, hypoplastic first metatarsal, lack of middle and distal phalanges in one supernumerary toe, three tarsal bones, hypoplastic middle phalanx and no distal phalanx for fourth toe, andno middle or distal phalanges for fifth toe. The fibula articulated with the anteromedial calcaneus and the tibia was completely absent. We identified numerous muscles and nerves in the superficial dissection that are described in the results section of the case report. Due to the rarity of this combination of anatomical findings, descriptions of such cases are very infrequent in the literature.展开更多
基金supported by NIH grant RO1 NS093985 (to DS, NZ, XW) and RO1 NS101955 (to DS)the VCU Microscopy Facility,supported,in part,by funding from NIH-NCI Cancer Center Support Grant P30 CA016059。
文摘Neovascularization and angiogenesis in the brain are important physiological processes for normal brain development and repair/regeneration following insults. Integrins are cell surface adhesion receptors mediating important function of cells such as survival, growth and development during tissue organization, differentiation and organogenesis. In this study, we used an integrin-binding array platform to identify the important types of integrins and their binding peptides that facilitate adhesion, growth, development, and vascular-like network formation of rat primary brain microvascular endothelial cells. Brain microvascular endothelial cells were isolated from rat brain on post-natal day 7. Cells were cultured in a custom-designed integrin array system containing short synthetic peptides binding to 16 types of integrins commonly expressed on cells in vertebrates. After 7 days of culture, the brain microvascular endothelial cells were processed for immunostaining with markers for endothelial cells including von Willibrand factor and platelet endothelial cell adhesion molecule. 5-Bromo-2′-dexoyuridine was added to the culture at 48 hours prior to fixation to assess cell proliferation. Among 16 integrins tested, we found that α5β1, αvβ5 and αvβ8 greatly promoted proliferation of endothelial cells in culture. To investigate the effect of integrin-binding peptides in promoting neovascularization and angiogenesis, the binding peptides to the above three types of integrins were immobilized to our custom-designed hydrogel in three-dimensional(3 D) culture of brain microvascular endothelial cells with the addition of vascular endothelial growth factor. Following a 7-day 3 D culture, the culture was fixed and processed for double labeling of phalloidin with von Willibrand factor or platelet endothelial cell adhesion molecule and assessed under confocal microscopy. In the 3 D culture in hydrogels conjugated with the integrin-binding peptide, brain microvascular endothelial cells formed interconnected vascular-like network with clearly discernable lumens, which is reminiscent of brain microvascular network in vivo. With the novel integrin-binding array system, we identified the specific types of integrins on brain microvascular endothelial cells that mediate cell adhesion and growth followed by functionalizing a 3 D hydrogel culture system using the binding peptides that specifically bind to the identified integrins, leading to robust growth and lumenized microvascular-like network formation of brain microvascular endothelial cells in 3 D culture. This technology can be used for in vitro and in vivo vascularization of transplants or brain lesions to promote brain tissue regeneration following neurological insults.
基金supported by grants from the Hunan Province Academic Degree and Graduate Education Reform Project(No.2020JGYB028)the National Natural Science Foundation of China(No.81971891,No.82172196,No.81772134)+1 种基金the Key Laboratory of Emergency and Trauma(Hainan Medical University)of the Ministry of Education(No.KLET-202108)the College Students'Innovation and Entrepreneurship Project(No.S20210026020013).
文摘Objective:The integration of training in theory and practice across the medical education spectrum is being encouraged to increase student understanding and skills in the sciences.This study aimed to determine the deciding factors that drive students'perceived advantages in class to improve precision education and the teaching model.Methods:A mixed strategy of an existing flipped classroom(FC)and a case-based learning(CBL)model was conducted in a medical morphology curriculum for 575 postgraduate students.The subjective learning evaluation of the individuals(learning time,engagement,study interest and concentration,and professional integration)was collected and analyzed after FC-CBL model learning.Results:The results from the general evaluation showed promising results of the medical morphology in the FC-CBL model.Students felt more engaged by instructors in person and benefited in terms of time-saving,flexible arrangements,and professional improvement.Our study contributed to the FC-CBL model in Research Design in postgraduate training in 4 categories:1)advancing a guideline of precision teaching according to individual characteristics;2)revealing whether a learning background is needed for a Research Design course to guide setting up a preliminary course;3)understanding the perceived advantages and their interfaces;and 4)barriers and/or improvement to implement the FC-CBL model in the Research Design class,such as a richer description of e-learning and hands-on practice.Conclusion:Undertaking a FC-CBL combined model could be a useful addition to pedagogy for medical morphology learning in postgraduate training.
基金supported by the Natural Science Foundation of Hunan Province,No.2021JJ30389(to JG)the Key Research and Development Program of Hunan Province of China,Nos.2022SK2042(to LL)and 2020SK2122(to ET)。
文摘Epilepsy is a neurological disorder characterized by high morbidity,high recurrence,and drug resistance.Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy.Metabotropic glutamate receptors(mGluRs)are G protein-coupled receptors activated by glutamate and are key regulators of neuronal and synaptic plasticity.Dysregulated mGluR signaling has been associated with various neurological disorders,and numerous studies have shown a close relationship between mGluRs expression/activity and the development of epilepsy.In this review,we first introduce the three groups of mGluRs and their associated signaling pathways.Then,we detail how these receptors influence epilepsy by describing the signaling cascades triggered by their activation and their neuroprotective or detrimental roles in epileptogenesis.In addition,strategies for pharmacological manipulation of these receptors during the treatment of epilepsy in experimental studies is also summarized.We hope that this review will provide a foundation for future studies on the development of mGluR-targeted antiepileptic drugs.
基金supported by the UTHSC Bridge funding award (E073005058 Bridge Support-2022)the National Institute of Health (R01-NS09 7800 and R56 NS127924-01) to TI。
文摘Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019).Although the only FDA-approved effective medication is tissue plasminogen activator(tPA),it should be administrated within 4.5 hours of ischemic stroke.Furthermore,tPA has been an integral part of managing acute ischemic stro ke.
基金National Natural Science Foundation of China,No.82172196,No.82372507,and No.81971891.
文摘In this editorial,we offer our perspective on the groundbreaking study entitled“Hypoxia and inflammatory factor preconditioning enhances the immunosup-pressive properties of human umbilical cord mesenchymal stem cells”,recently published in World Journal of Stem Cells.Despite over three decades of research on the clinical application of mesenchymal stem cells(MSCs),only a few therapeutic products have made it to clinical use,due to multiple preclinical and clinical challenges yet to be addressed.The study proved the hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics,which revealed the combination of inflammatory factors and hypoxic preconditioning offers a promising approach to enhance the function of MSCs.As we delve deeper into the intricacies of pretreat-ment methodologies,we anticipate a transformative shift in the landscape of MSC-based therapies,ultimately contributing to improved patient outcomes and advancing the field as a whole.
文摘The efficacy of electroacupuncture in the treatment of peripheral facial paralysis is known, but the specific mechanism has not been clarified. Glial cell-derived neurotrophic factor(GDNF) has been shown to protect neurons by binding to N-cadherin. Our previous results have shown that electroacupuncture could increase the expression of N-cadherin mRNA in facial neurons and promote facial nerve regeneration. In this study, the potential mechanisms by which electroacupuncture promotes nerve regeneration were elucidated through assessing the effects of electroacupuncture on GDNF and N-cadherin expression in facial motoneurons of rabbits with peripheral facial nerve crush injury. New Zealand rabbits were randomly divided into a normal group(normal control, n = 21), injury group(n = 45) and electroacupuncture group(n = 45). Model rabbits underwent facial nerve crush injury only. Rabbits in the electroacupuncture group received facial nerve injury, and then underwent electroacupuncture at Yifeng(TE17), Jiache(ST6), Sibai(ST2), Dicang(ST4), Yangbai(GB14), Quanliao(SI18), and Hegu(LI4; only acupuncture, no electrical stimulation). The results showed that in behavioral assessments, the total scores of blink reflex, vibrissae movement, and position of apex nasi, were markedly lower in the EA group than those in the injury group. Hematoxylin-eosin staining of the right buccinator muscle of each group showed that the cross-sectional area of buccinator was larger in the electroacupuncture group than in the injury group on days 1, 14 and 21 post-surgery. Toluidine blue staining of the right facial nerve tissue of each group revealed that on day 14 post-surgery, there was less axonal demyelination and fewer inflammatory cells in the electroacupuncture group compared with the injury group. Quantitative real time-polymerase chain reaction showed that compared with the injury group, N-cadherin mRNA levels on days 4, 7, 14 and 21 and GDNF mRNA levels on days 4, 7 and 14 were significantly higher in the electroacupuncture group. Western blot assay displayed that compared with the injury group, the expression of GDNF protein levels on days 7, 14 and 21 were significantly upregulated in the electroacupuncture group. The histology with hematoxylin-eosin staining and Nissl staining of brainstem tissues containing facial neurons in the middle and lower part of the pons exhibited that on day 7 post-surgery, there were significantly fewer apoptotic neurons in the electroacupuncture group than in the injury group. By day 21, there was no significantly difference in the number of neurons between the electroacupuncture and normal groups. Taken together, these results have confirmed that electroacupuncture promotes regeneration of peripheral facial nerve injury in rabbits, inhibits neuronal apoptosis, and reduces peripheral inflammatory response, resulting in the recovery of facial muscle function. This is achieved by up-regulating the expression of GDNF and N-cadherin in central facial neurons.
基金financially supported by the Natural Science Foundation of Education Department of Sichuan Province of China,No.14ZB0152the Joint Research Program of Luzhou and Southwest Medical University,in China,No.14JC0120
文摘Nicotiflorin is a flavonoid extracted from Carthamus tinctorius.Previous studies have shown its cerebral protective effect,but the mechanism is undefined.In this study,we aimed to determine whether nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis through the JAK2/STAT3 pathway.The cerebral ischemia/reperfusion injury model was established by middle cerebral artery occlusion/reperfusion.Nicotiflorin(10 mg/kg) was administered by tail vein injection.Cell apoptosis in the ischemic cerebral cortex was examined by hematoxylin-eosin staining and terminal deoxynucleotidyl transferase d UTP nick end labeling assay.Bcl-2 and Bax expression levels in ischemic cerebral cortex were examined by immunohistochemial staining.Additionally,p-JAK2,p-STAT3,Bcl-2,Bax,and caspase-3 levels in ischemic cerebral cortex were examined by western blot assay.Nicotiflorin altered the shape and structure of injured neurons,decreased the number of apoptotic cells,down-regulates expression of p-JAK2,p-STAT3,caspase-3,and Bax,decreased Bax immunoredactivity,and increased Bcl-2 protein expression and immunoreactivity.These results suggest that nicotiflorin protects against cerebral ischemia/reperfusion injury-induced apoptosis via the JAK2/STAT3 pathway.
基金supported by grants from the National Natural Science Foundation of China,No.30971531,81070987
文摘Ginsenoside Rb1 has been reported to exert anti-aging and anti-neurodegenerative effects. In the present study, we investigate whether ginsenoside Rb1 is involved in neurite outgrowth and neuroprotection against damage induced by amyloid beta(25–35) in cultured hippocampal neurons, and explore the underlying mechanisms. Ginsenoside Rb1 significantly increased neurite outgrowth in hippocampal neurons, and increased the expression of phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2. These effects were abrogated by API-2 and PD98059, inhibitors of the signaling proteins Akt and MEK. Additionally, cultured hippocampal neurons were exposed to amyloid beta(25–35) for 30 minutes; ginsenoside Rb1 prevented apoptosis induced by amyloid beta(25–35), and this effect was blocked by API-2 and PD98059. Furthermore, ginsenoside Rb1 significantly reversed the reduction in phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2 levels induced by amyloid beta(25–35), and API-2 neutralized the effect of ginsenoside Rb1. The present results indicate that ginsenoside Rb1 enhances neurite outgrowth and protects against neurotoxicity induced by amyloid beta(25–35) via a mechanism involving Akt and extracellular signal-regulated kinase 1/2 signaling.
基金supported by the National Natural Science Foundation of China,No.81571939(to KX),81601719(to JZ)and 81772134(to KX)Key Research and Development Program of Hunan Province of China,No.2018SK2091(to KX)+1 种基金Wu Jie-Ping Medical Foundation of the Minister of Health of China,No.320.6750.14118(to KX)Teacher Research Foundation of Central South University of China,No.2014JSJJ026(to KX)
文摘Long non-coding RNAs(lncRNAs) play a key role in craniocerebral disease, although their expression profiles in human traumatic brain injury are still unclear. In this regard, in this study, we examined brain injury tissue from three patients of the 101 st Hospital of the People's Liberation Army, China(specifically, a 36-year-old male, a 52-year-old female, and a 49-year-old female), who were diagnosed with traumatic brain injury and underwent brain contusion removal surgery. Tissue surrounding the brain contusion in the three patients was used as control tissue to observe expression characteristics of lncRNAs and mRNAs in human traumatic brain injury tissue. Volcano plot filtering identified 99 lncRNAs and 63 mRNAs differentially expressed in frontotemporal tissue of the two groups(P < 0.05, fold change > 1.2). Microarray analysis showed that 43 lncRNAs were up-regulated and 56 lncRNAs were down-regulated. Meanwhile, 59 mRNAs were up-regulated and 4 mRNAs were down-regulated. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses revealed 27 signaling pathways associated with target genes and, in particular, legionellosis and influenza A signaling pathways. Subsequently, a lncRNA-gene network was generated, which showed an absolute correlation coefficient value > 0.99 for 12 lncRNA-mRNA pairs. Finally, quantitative real-time polymerase chain reaction confirmed different expression of the five most up-regulated mRNAs within the two groups, which was consistent with the microarray results. In summary, our results show that expression profiles of mRNAs and lncRNAs are significantly different between human traumatic brain injury tissue and surrounding tissue, providing novel insight regarding lncRNAs' involvement in human traumatic brain injury. All participants provided informed consent. This research was registered in the Chinese Clinical Trial Registry(registration number: ChiCTR-TCC-13004002) and the protocol version number is 1.0.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(2018R1D1A1B07040282 to JJ)+1 种基金a grant from Kyung Hee University in 2018(KHU-20181065 to JJ)
文摘A Schwann cell has regenerative capabilities and is an important cell in the peripheral nervous system.This microarray study is part of a bioinformatics study that focuses mainly on Schwann cells. Microarray data provide information on differences between microarray-based and experiment-based gene expression analyses. According to microarray data, several genes exhibit increased expression(fold change) but they are weakly expressed in experimental studies(based on morphology, protein and mRNA levels). In contrast, some genes are weakly expressed in microarray data and highly expressed in experimental studies;such genes may represent future target genes in Schwann cell studies. These studies allow us to learn about additional genes that could be used to achieve targeted results from experimental studies. In the current big data study by retrieving more than 5000 scientific articles from PubMed or NCBI, Google Scholar, and Google, 1016(up-and downregulated) genes were determined to be related to Schwann cells. However,no experiment was performed in the laboratory; rather, the present study is part of a big data analysis. Our study will contribute to our understanding of Schwann cell biology by aiding in the identification of genes.Based on a comparative analysis of all microarray data, we conclude that the microarray could be a good tool for predicting the expression and intensity of different genes of interest in actual experiments.
基金supported by China Postdoctoral Science Foundation,No.2016M590757the Postdoctoral Science Foundation of Xiangya Hospital of Central South University of China,No.20+4 种基金the Hunan Provincial Natural Science Foundation of China,No.2015JJ6010a grant from the Basic Research Program of Science and Technology Commission Foundation of Hunan Province of China,No.2015JC3059the Project Fund of the Department of Education in Hunan Province of China,No.15A023,13C1107the Scientific Research Project Fund of Health Department of Hunan Province of China,No.B2011-071,B2016096a grant from the Construction Program of the Key Discipline in Hunan Province of China
文摘The principal pathology of Alzheimer's disease includes neuronal extracellular deposition of amyloid-beta peptides and formation of senile pl aques,which in turn induce neuroinflammation in the brain.Triptolide,a natural extract from the vine-like herb Tripterygium wilfordii Hook F,has potent anti-inflammatory and immunosuppressive efficacy.Therefore,we determined if triptolide can inhibit activation and proliferation of microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer's disease.We used 1 or 5 μg/kg/d triptolide to treat APP/PS1 double transgenic mice(aged 4–4.5 months) for 45 days.Unbiased stereology analysis found that triptolide dose-dependently reduced the total number of microglial cells,and transformed microglial cells into the resting state.Further,triptolide(5 μg/kg/d) also reduced the total number of hippocampal astrocytes.Our in vivo test results indicate that triptolide suppresses activation and proliferation of microglial cells and astrocytes in the hippocampus of APP/PS1 double transgenic mice with Alzheimer's disease.
基金supported by the National Natural Science Foundation of China,Nos. 81772134,81971891,and 81571939 (to KX)the Key Research and Development Program of Hunan Province of China,No. 2018SK2091 (to KX)+3 种基金Hunan Provincial Innovation Foundation For Postgraduate,No. CX20200116 (to WTY)Wu Jie Ping Medical Foundation of the Minister of Health of China,No. 320.6750.14118 (to KX)Foundation of Science and Technology of Hunan Province of China,No. 2018JJ2552 (to YC)the Project of Graduate Independent Exploration and Innovation Plan of Central South University of China,No. 2020zzts218 (to WTY)。
文摘There are two types of cell death-apoptosis and necrosis. Apoptosis is cell death regulated by cell signaling pathways, while necrosis has until recently been considered a passive mechanism of cell death caused by environmental pressures. However, recent studies show that necrosis can also be regulated by specific cell signaling pathways. This mode of death, termed necroptosis, has been found to be related to the occurrence and development of many diseases. We used bibliometrics to analyze the global output of literature on necroptosis in the field of neuroscience published in the period 2007–2019 to identify research hotspots and prospects. We included 145 necroptosisrelated publications and 2239 references published in the Web of Science during 2007–2019. Visualization analysis revealed that the number of publications related to necroptosis has increased year by year, reaching a peak in 2019. China is the country with the largest number of publications. Key word and literature analyses demonstrated that mitochondrial function change, stroke, ischemia/reperfusion and neuroinflammation are likely the research hotspots and future directions of necroptosis research in the nervous system. The relationship between immune response-related factors, damage-associated molecular patterns, pathogen-associated molecular patterns and necroptosis may become a potential research hotspot in the future. Taken together, our findings suggest that although the inherent limitations of bibliometrics may affect the accuracy of the literature-based prediction of research hotspots, the results obtained from the included publications can provide a reference for the study of necroptosis in the field of neuroscience.
基金the National Natural Science Foundation of China,No.30900773the Natural Science Foundation of Hunan Province in China,No.11JJ2020Young Teachers Training Program of University of Hunan Province
文摘Previous studies have demonstrated that doublecortin-positive immature neurons exist predominantly in the superficial layer of the cerebral cortex of adult mammals such as guinea pigs, and these neurons exhibit very weak properties of self-proliferation during adulthood under physiological conditions. To verify whether environmental enrichment has an impact on the proliferation and maturation of these immature neurons in the prefrontal cortex of adult guinea pigs, healthy adult guinea pigs were subjected to short-term environmental enrichment. Animals were allowed to play with various cognitive and physical stimulating objects over a period of 2 weeks, twice per day, for 60 minutes each. Immunofluorescence staining results indicated that the number of doublecortin-positive cells in layer II of the prefrontal cortex was significantly increased after short-term environmental enrichment exposure. In addition, these doublecortin-positive cells co-expressed 5-bromo-2-deoxyuridine(a marker of cell proliferation), c-Fos(a marker of cell viability) and NeuN(a marker of mature neurons). Experimental findings showed that short-term environmental enrichment can induce proliferation, activation and maturation of doublecortin-positive cells in layer II of the prefrontal cortex of adult guinea pigs.
基金the Guangdong Natural Science Foundation of China,No.S2011040004372the Fundamental Research Funds for the Central Universities,No.11ykpy05
文摘Nestin+ neurons have been shown to express choline acetyltransferase(ChAT) in the medial septum-diagonal band of Broca in adult rats. This study explored the projection of nestin+ neurons to the olfactory bulb and the time course of nestin+ neurons in the medial septum-diagonal band of Broca in adult rats during injury recovery after olfactory nerve transection. This study observed that all nestin+ neurons were double-labeled with ChAT in the medial septum-diagonal band of Broca. Approximately 53.6% of nestin+ neurons were projected to the olfactory bulb and co-labeled with fast blue. A large number of nestin+ neurons were not present in each region of the medial septum-diagonal band of Broca. Nestin+ neurons in the medial septum and vertical limb of the diagonal band of Broca showed obvious compensatory function. The number of nestin+ neurons decreased to a minimum later than nestin–/ChAT+ neurons in the medial septum-diagonal band of Broca. The results suggest that nestin+ cholinergic neurons may have a closer connection to olfactory bulb neurons. Nestin+ cholinergic neurons may have a stronger tolerance to injury than Nestin–/ChAT+ neurons. The difference between nestin+ and nestin–/ ChAT+ neurons during the recovery process requires further investigations.
基金supported by the National Natural Science Foundation of China(Nos.81572150,81571939)the Natural Science Foundation of Hunan Province(No.2015JJ2187)the Wu Jie-Ping Medical Foundation of the Minister of Health of China(No.320675014118)
文摘This study aimed to examine the biocompatibility of calcium titanate(CaTiO_3) coating prepared by a simplified technique in an attempt to assess the potential of CaTiO_3 coating as an alternative to current implant coating materials. CaTiO_3-coated titanium screws were implanted with hydroxyapatite(HA)-coated or uncoated titanium screws into medial and lateral femoral condyles of 48 New Zealand white rabbits. Imaging, histomorphometric and biomechanical analyses were employed to evaluate the osseointegration and biocompatibility 12 weeks after the implantation. Histology and scanning electron microscopy revealed that bone tissues surrounding the screws coated with CaTiO_3 were fully regenerated and they were also well integrated with the screws. An interfacial fibrous membrane layer, which was found in the HA coating group, was not noticeable between the bone tissues and CaTiO_3-coated screws. X-ray imaging analysis showed in the CaTiO_3 coating group, there was a dense and tight binding between implants and the bone tissues; no radiation translucent zone was found surrounding the implants as well as no detachment of the coating and femoral condyle fracture. In contrast, uncoated screws exhibited a fibrous membrane layer, as evidenced by the detection of a radiation translucent zone between the implants and the bone tissues. Additionally, biomechanical testing revealed that the binding strength of CaTiO_3 coating with bone tissues was significantly higher than that of uncoated titanium screws, and was comparable to that of HA coating. The study demonstrated that CaTiO_3 coating in situ to titanium screws possesses great biocompatibility and osseointegration comparable to HA coating.
文摘Over the past two decades,many investigators have reported how extracellular matrix molecules act to regulate neuroplasticity.The majority of these studies involve proteins which are targets of matrix metalloproteinases.Importantly,these enzyme/substrate interactions can regulate degenerative and regenerative phases of synaptic plasticity,directing axonal and dendritic reorganization after brain insult.The present review first summarizes literature support for the prominent role of matrix metalloproteinases during neuroregeneration,followed by a discussion of data contrasting adaptive and maladaptive neuroplasticity that reveals time-dependent metalloproteinase/substrate regulation of postinjury synaptic recovery.The potential for these enzymes to serve as therapeutic targets for enhanced neuroplasticity after brain injury is illustrated with experiments demonstrating that metalloproteinase inhibitors can alter adaptive and maladaptive outcome.Finally,the complexity of metalloproteinase role in reactive synaptogenesis is revealed in new studies showing how these enzymes interact with immune molecules to mediate cellular response in the local regenerative environment,and are regulated by novel binding partners in the brain extracellular matrix.Together,these different examples show the complexity with which metalloproteinases are integrated into the process of neuroregeneration,and point to a promising new angle for future studies exploring how to facilitate brain plasticity.
基金supported by the National Natural Science Foundation of China, No. 81171461, 30900773the Natural Science Foundation of Hunan Province, No.10JJ3038, 11JJ2020"125 Tenant Project" of the Third Xiangya Hospital
文摘Recently, epidemiological studies on the etiology of peripheral neuropathies have revealed that hyperlipidemia is a novel risk factor. Plasma lipid levels were confirmed to be associated with the incidence of many peripheral neuropathies including axonal distal polyneuropathy, vision and hearing loss, motor nerve system lesions and sympathetic nerve system dysfunction. Moreover, different lipid components such as cholesterol, triacylglycerols and lipoprotein are involved in the pathogenesis of these neuropathies. This review aimed to discuss the effect of hyperlipidemia on the peripheral nervous system and its association with peripheral neuropathies. Furthermore, a detailed discussion focusing on the explicit mechanisms related to hyperlipidemia-induced peripheral neuropathies is presented here. These mechanisms, including intracellular oxidative stress, inflammatory lesions, ischemia and dysregulation of local lipid metabolism, share pathways and interact mutually. In addition, we examined current information on clinical trials to prevent and treat peripheral neuropathies caused by hyperlipidemia, with a predictive discussion regarding the orientation of future investigations.
基金supported by the National Natural Science Foundation of China, No. 81070897, 81102726
文摘In this study, a rat model of inflammatory pain was produced by injecting complete Freund's adjuvant into the hind paw, and the expression of acetylated histone 3 in the spinal cord dorsal horn was examined using immunohistochemical staining. One day following injection, there was a dramatic decrease in acetylated histone 3 expression in spinal cord dorsal horn neurons. However, on day 7, expression recovered in adjuvant-injected rats. While acetylated histone 3 labeling was present in dorsal horn neurons, it was more abundant in astrocytes and microglial cells. The recovery of acetylated histone 3 expression was associated with a shift in expression of the protein from neurons to glial cells. Morphine injection significantly upregulated the expression of acetylated histone 3 in spinal cord dorsal horn neurons and glial cells 1 day after injection, especially in astrocytes, preventing the transient downregulation. Our results indicate that inflammatory pain induces a transient downregulation of acetylated histone 3 in the spinal cord dorsal horn at an early stage following adjuvant injection, and that this effect can be reversed by morphine. Thus, the downregulation of acetylated histone 3 may be involved in the development of inflammatory pain.
文摘Objective The purpose of this study is to identify the molecular basis of the contacting -neuron membrane K+ conductance in glia cells of native bovine retina. Methods RT-PCR, Northern blot and Western blot analyses were used to detect the expression of the inwardly rectifying K+ (Kir) channel subunits Kir2.1 in native bovine RPE and neural retina. The distribution of Kir2.1 protein was determined in frozen sections of bovine retina-RPEchoroid by indirect immunofluorescence analysis. Results RT-PCR analysis reveals Kir2.1 transcript in both RPE and neural retina. In Northern blots, Kir2.1 probe hybridizes to an appropriately sized-transcript in neural retina but not in RPE. In Western blots, Kir2.1 antibody recognizes a major monomer of about 60 kDa in neural retina but not in RPE. Immunofluorescence reveals that Kir2.1 immunostaining is expressed at many parts of Muller cells, especially in the membrane domains of Muller cells that contact retinal neurons, i. e. , along the two stem processes,over the soma, and in the side branches extending into the synaptic layers. No immunostaining is seen in RPE. Doubling staining shows that Kir2.1 proteins and glutamine synthetase proteins which are a marker of Muller cell co-localized well. Conclusions These results reveal that Kir2.1 is localized in the Muller cells, no Kir2.1 in RPE. These data suggests that Kir2.1 may be involved in the transport of K+ in the bovine neural retina.
文摘A seven-month old female presented with left tibial hemimelia(or congenital tibial aplasia; Weber type VIIb, Jones et al type 1a), seven-toed preaxial polydactyly, and severe club foot(congenital talipes equinovarus). Definitive amputation surgery disarticulated the lower limb at the knee. This case report describes the anatomical findings of a systematic post-amputation examination of the lower limb's superficial dissection, X-ray s, and computed to mography (CT) scans. From the X-rays and CT scans, we found curved and overlapping preaxial supernumerary toes, hypoplastic first metatarsal, lack of middle and distal phalanges in one supernumerary toe, three tarsal bones, hypoplastic middle phalanx and no distal phalanx for fourth toe, andno middle or distal phalanges for fifth toe. The fibula articulated with the anteromedial calcaneus and the tibia was completely absent. We identified numerous muscles and nerves in the superficial dissection that are described in the results section of the case report. Due to the rarity of this combination of anatomical findings, descriptions of such cases are very infrequent in the literature.
