The intrinsic ability of peripheral nerves to regenerate after injury is extremely limited,especially in case of severe injury.This often leads to poor motor function and permanent disability.Existing approaches for t...The intrinsic ability of peripheral nerves to regenerate after injury is extremely limited,especially in case of severe injury.This often leads to poor motor function and permanent disability.Existing approaches for the treatment of injured nerves do not provide appropriate conditions to support survival and growth of nerve cells.This drawback can be compensated by the use of gene therapy and cell therapy-based drugs that locally provide an increase in the key regulators of nerve growth,including neurotrophic factors and extracellular matrix proteins.Each growth factor plays its own specific angiotrophic or neurotrophic role.Currently,growth factors are widely studied as accelerators of nerve regeneration.Particularly noteworthy is synergy between various growth factors,that is essential for both angiogenesis and neurogenesis.Fibroblast growth factor 2 and vascular endothelial growth factor are widely known for their proangiogenic effects.At the same time,fibroblast growth factor 2 and vascular endothelial growth factor stimulate neural cell growth and play an important role in neurodegenerative diseases of the peripheral nervous system.Taken together,their neurotrophic and angiogenic properties have positive effect on the regeneration process.In this review we provide an in-depth overview of the role of fibroblast growth factor 2 and vascular endothelial growth factor in the regeneration of peripheral nerves,thus demonstrating their neurotherapeutic efficacy in improving neuron survival in the peripheral nervous system.展开更多
Neuregulin-1 type Ⅲ is a key regulator in Schwann cell proliferation, committing to a myelinat- ing fate and regulating myelin sheath thickness. However, the expression pattern of neuregulin- 1 type III in the periph...Neuregulin-1 type Ⅲ is a key regulator in Schwann cell proliferation, committing to a myelinat- ing fate and regulating myelin sheath thickness. However, the expression pattern of neuregulin- 1 type III in the peripheral nervous system during developmental periods (such as the premyelin- ating stage, myelinating stage and postmyelinating stage) has rarely been studied. In this study, dorsal root ganglia were isolated from rats between postnatal day 1 and postnatal day 56. The expression pattern of neuregulin-1 type III in dorsal root ganglia neurons at various develop- mental stages were compared by quantitative real-time polymerase chain reaction, western blot assay and immunofluorescent staining. The expression of neuregulin-I type Ⅲ mRNA reached its peak at postnatal day 3 and then stabilized at a relative high expression level from postnatal day 3 to postnatal day 56. The expression of neuregulin-1 type III protein increased gradually from postnatal day 1, reached a peak at postnatal day 28, and then decreased at postnatal day 56. Immunofluorescent staining results showed a similar tendency to western blot assay results. Experimental findings indicate that the expression of neuregulin-1 type III in rat dorsal root ganglion was increased during the premyelinating (from postnatal day 2 to postnatal day 5) and myelinating stage (from postnatal day 5 to postnatal day 10), but remained at a high level in the postmyelinating stage (after postnatal day 10).展开更多
Cerebrolysin is a drug consisting of low-molecular-weight neurotrophic peptides and free amino acids. Cerebrolysin has been shown to ameliorate the effects of oxidative stress, reduce apoptosis, and promote neuronal g...Cerebrolysin is a drug consisting of low-molecular-weight neurotrophic peptides and free amino acids. Cerebrolysin has been shown to ameliorate the effects of oxidative stress, reduce apoptosis, and promote neuronal growth in several degenerative and acquired central nervous system insults, including dementias, stroke, and traumatic injuries. Little is known about its therapeutic efficacy in peripheral nervous system diseases. In this study, we clinically evaluated the effects of cerebrolysin on peripheral nervous system lesions. We evaluated the clinical efficacy of cerebrolysin in six patients with the following conditions who failed to respond to conventional therapies: (1) atonic bladder due to inflammatory radiculitis; (2) paraplegia due to inflammatory radiculoneuropathy; (3) post-traumatic brachial plexopathy; (4) compressive radial nerve injury; (5) post-traumatic facial nerve paralysis; and (6) diabetic ophthalmoplegia. Our results showed that cerebrolysin was more associated with rapid neurological recovery after various peripheral nerve lesions than other therapies including steroids and supportive therapies such as vitamins and antioxidants. The present results support the therapeutic efficacy of cerebrolysin in the treatment of acquired peripheral nervous system diseases.展开更多
Most researchers believe that neurogenesis in mature mammals is restricted only to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle in the central nervous system. In the p...Most researchers believe that neurogenesis in mature mammals is restricted only to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle in the central nervous system. In the peripheral nervous system, neurogenesis is thought to be active only during prenatal development, with the exception of the olfactory neuroepithelium. However, sensory ganglia in the adult peripheral nervous system have been reported to contain precursor cells that can proliferate in vitro and be induced to differentiate into neurons. The occurrence of insult-induced neurogenesis, which has been reported by several investigators in the brain, is limited to a few recent reports for the peripheral nervous system. These reports suggest that damage to the adult nervous system induces mechanisms similar to those that control the generation of new neurons during prenatal development. Understanding conditions under which neurogenesis can be induced in physiologically non-neurogenic regions in adults is one of the major challenges for developing therapeutic strategies to repair neurological damage. However, the induced neurogenesis in the peripheral nervous system is still largely unexplored. This review presents the history of research on adult neurogenesis in the peripheral nervous system, which dates back more than 100 years and reveals the evidence on the under estimated potential for generation of new neurons in the adult peripheral nervous system.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
Traumatic cerebral or spinal cord injury induced by military,traffic,and sports accidents,falls or environmental and anthropogenic catastrophes are among main causes of people mortality and disability,especially in yo...Traumatic cerebral or spinal cord injury induced by military,traffic,and sports accidents,falls or environmental and anthropogenic catastrophes are among main causes of people mortality and disability,especially in young and middle age men(Kobeissy,2015).Axon transection,or axotomy,occurs in wounds and during surgery.展开更多
The peripheral nervous system(PNS)is a fascinatingly complex and crucial component of the human body,responsible for transmitting vital signals throughout the body's intricate network of nerves.Its efficient funct...The peripheral nervous system(PNS)is a fascinatingly complex and crucial component of the human body,responsible for transmitting vital signals throughout the body's intricate network of nerves.Its efficient functioning is paramount to our health,with any dysfunction often resulting in serious medical conditions,including motor disorders,neurological diseases,and psychiatric disorders.Recent strides in science and technology have made neuromodulation of the PNS a promising avenue for addressing these health issues.Neuromodulation involves modifying nerve activity using a range of techniques,such as electrical,chemical,optical,and mechanical stimulation.Bioelectronics plays a critical role in this effort,allowing for precise,controlled,and sustained stimulation of the PNS.This paper provides an overview of the PNS,discusses the current state of neuromodulation devices,and presents emerging trends in the field,including advances in wireless power transfer and materials,that are shaping the future of neuromodulation.展开更多
Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes...Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.展开更多
Vimentin is a major type Ⅲ intermediate filament protein that plays important roles in several basic cellular functions including cell migration, proliferation, and division. Although vimentin is a cytoplasmic protei...Vimentin is a major type Ⅲ intermediate filament protein that plays important roles in several basic cellular functions including cell migration, proliferation, and division. Although vimentin is a cytoplasmic protein, it also exists in the extracellular matrix and at the cell surface. Previous studies have shown that vimentin may exert multiple physiological effects in different nervous system injuries and diseases. For example, the studies of vimentin in spinal cord injury and stroke mainly focus on the formation of reactive astrocytes. Reduced glial scar, increased axonal regeneration, and improved motor function have been noted after spinal cord injury in vimentin and glial fibrillary acidic protein knockout(GFAPVIM) mice. However, attenuated glial scar formation in post-stroke in GFAP–/– VIM–/– mice resulted in abnormal neuronal network restoration and worse neurological recovery. These opposite results have been attributed to the multiple roles of glial scar in different temporal and spatial conditions. In addition, extracellular vimentin may be a neurotrophic factor that promotes axonal extension by interaction with the insulin-like growth factor 1 receptor. In the pathogenesis of bacterial meningitis, cell surface vimentin is a meningitis facilitator, acting as a receptor of multiple pathogenic bacteria, including E. coli K1, Listeria monocytogenes, and group B streptococcus. Compared with wild type mice, VIMmice are less susceptible to bacterial infection and exhibit a reduced inflammatory response, suggesting that vimentin is necessary to induce the pathogenesis of meningitis. Recently published literature showed that vimentin serves as a double-edged sword in the nervous system, regulating axonal regrowth, myelination, apoptosis, and neuroinflammation. This review aims to provide an overview of vimentin in spinal cord injury, stroke, bacterial meningitis, gliomas, and peripheral nerve injury and to discuss the potential therapeutic methods involving vimentin manipulation in improving axonal regeneration, alleviating infection, inhibiting brain tumor progression, and enhancing nerve myelination.展开更多
Paired immunoglobulin-like receptor B(Pir B) is a functional receptor of myelin-associated inhibitors for axonal regeneration and synaptic plasticity in the central nervous system, and thus suppresses nerve regenera...Paired immunoglobulin-like receptor B(Pir B) is a functional receptor of myelin-associated inhibitors for axonal regeneration and synaptic plasticity in the central nervous system, and thus suppresses nerve regeneration. The regulatory effect of Pir B on injured nerves has received a lot of attention. To better understand nerve regeneration inability after spinal cord injury, this study aimed to investigate the distribution of Pir B(via immunofluorescence) in the central nervous system and peripheral nervous system 10 days after injury. Immunoreactivity for Pir B increased in the dorsal root ganglia, sciatic nerves, and spinal cord segments. In the dorsal root ganglia and sciatic nerves, Pir B was mainly distributed along neuronal and axonal membranes. Pir B was found to exhibit a diffuse, intricate distribution in the dorsal and ventral regions. Immunoreactivity for Pir B was enhanced in some cortical neurons located in the bilateral precentral gyri. Overall, the findings suggest a pattern of Pir B immunoreactivity in the nervous system after unilateral spinal transection injury, and also indicate that Pir B may suppress repair after injury.展开更多
Tau, a primary component of microtubule-associated protein, promotes microtubule assembly and/or disassembly and maintains the stability of the microtubule structure. Although the importance of tau in neurodegenerativ...Tau, a primary component of microtubule-associated protein, promotes microtubule assembly and/or disassembly and maintains the stability of the microtubule structure. Although the importance of tau in neurodegenerative diseases has been well demonstrated, wheth- er tau is involved in peripheral nerve regeneration remains unknown. In the current study, we obtained sciatic nerve tissue from adult rats 0, 1, 4, 7, and 14 days after sciatic nerve crush and examined tau mRNA and protein expression levels and the location of tau in the sciatic nerve following peripheral nerve injury. The results from our quantitative reverse transcription polymerase chain reaction analysis showed that compared with the uninjured control sciatic nerve, mRNA expression levels for both tau and tau tubulin kinase 1, a serine/ threonine kinase that regulates tau phosphorylation, were decreased following peripheral nerve injury. Our western blot assay results suggested that the protein expression levels of tau and phosphorylated tau initially decreased 1 day post nerve injury but then gradually increased. The results of our immunohistochemical labeling showed that the location of tau protein was not altered by nerve injury. Thus, these results showed that the expression of tau was changed following sciatic nerve crush, suggesting that tau may be involved in periph- eral nerve repair and regeneration.展开更多
Peripheral nerve fibroblasts play a critical role in nerve development and regeneration.Our previous study found that peripheral nerve fibroblasts have different sensory and motor phenotypes.Fibroblasts of different p...Peripheral nerve fibroblasts play a critical role in nerve development and regeneration.Our previous study found that peripheral nerve fibroblasts have different sensory and motor phenotypes.Fibroblasts of different phenotypes can guide the migration of Schwann cells to the same sensory or motor phenotype.In this study,we analyzed the different effects of peripheral nerve-derived fibroblasts and cardiac fibroblasts on motoneurons.Compared with cardiac fibroblasts,peripheral nerve fibroblasts greatly promoted motoneuron neurite outgrowth.Transcriptome analysis results identified 491 genes that were differentially expressed in peripheral nerve fibroblasts and cardiac fibroblasts.Among these,130 were significantly upregulated in peripheral nerve fibroblasts compared with cardiac fibroblasts.These genes may be involved in axon guidance and neuron projection.Three days after sciatic nerve transection in rats,peripheral nerve fibroblasts accumulated in the proximal and distal nerve stumps,and most expressed brain-derived neurotrophic factor.In vitro,brain-derived neurotrophic factor secreted from peripheral nerve fibroblasts increased the expression ofβ-actin and F-actin through the extracellular regulated protein kinase and serine/threonine kinase pathways,and enhanced motoneuron neurite outgrowth.These findings suggest that peripheral nerve fibroblasts and cardiac fibroblasts exhibit different patterns of gene expression.Peripheral nerve fibroblasts can promote motoneuron neurite outgrowth.展开更多
The peripheral nervous system has an extensive branching organization, and peripheral nerve injuries that ablate branch points present a complex challenge for clinical repair. Ablations of linear segments of the PNS h...The peripheral nervous system has an extensive branching organization, and peripheral nerve injuries that ablate branch points present a complex challenge for clinical repair. Ablations of linear segments of the PNS have been extensively studied and routinely treated with autografts, acellular nerve allografts, conduits, wraps, and nerve transfers. In contrast, segmental-loss peripheral nerve injuries, in which one or more branch points are ablated so that there are three or more nerve endings, present additional complications that have not been rigorously studied or documented. This review discusses:(1) the branched anatomy of the peripheral nervous system,(2) case reports describing how peripheral nerve injuries with branched ablations have been surgically managed,(3) factors known to influence regeneration through branched nerve structures,(4) techniques and models of branched peripheral nerve injuries in animal models, and(5) conclusions regarding outcome measures and studies needed to improve understanding of regeneration through ablated branched structures of the peripheral nervous system.展开更多
It is today widely acknowledged that nerve repair is now more than a matter of perfect microsurgical reconstruction only and that, to further improve clinical outcome, the involvement of different scientific disciplin...It is today widely acknowledged that nerve repair is now more than a matter of perfect microsurgical reconstruction only and that, to further improve clinical outcome, the involvement of different scientific disciplines is required. This evolving reconstructive/regenerative approach is based on the interdisciplinary and integrated pillars of tissue engineering such as reconstructive microsurgery, transplantation and biomaterials. In this paper, some of the most promising innovations for the tissue engineering of nerves, emerging from basic science investigation, are critically overviewed with special focus on those approaches that appear today to be more suitable for clinical translation.展开更多
BACKGROUND Vasculitis,a systemic disorder with inflammation of blood vessel walls,can develop broad spectrum of signs and symptoms according to involvement of various organs,and therefore,early diagnosis of vasculitis...BACKGROUND Vasculitis,a systemic disorder with inflammation of blood vessel walls,can develop broad spectrum of signs and symptoms according to involvement of various organs,and therefore,early diagnosis of vasculitis is challenging.We herein describe a patient who developed a special case of systemic vasculitis with mononeuropathy multiplex,rectal perforation and antiphospholipid syndrome(APS)presented with pulmonary embolism.CASE SUMMARY A 61-year-old woman visited hospital with complaints of myalgia and occasional fever.She was initially diagnosed as proctitis and treated with antibiotics,however,there was no improvement.In addition,she also complained right foot drop with hypesthesia,and left 2^(nd) and 3^(rd) finger tingling sensation.She underwent nerve conduction study for evaluation,and it revealed sensorimotor polyneuropathy in the left arm and bilateral legs.Subsequent sural nerve biopsy strongly suggested vasculitic neuropathy.Based on nerve biopsy and clinical manifestation,she was diagnosed with vasculitis and treated with immunosuppressive therapy.During treatment,sudden rectal perforation and pulmonary thromboembolism occurred,and further laboratory study suggested probable concomitant APS.Emergency Hartmann operation was performed for rectal perforation,and anti-coagulation therapy was started for APS.After few cycles of immunosuppressive therapy,tingling sensation and weakness in her hand and foot had been partially recovered and vasculitis was considered to be stationary.CONCLUSION Vasculitis can be presented with a variety of signs and symptoms,therefore,clinicians should always consider the possibility of diagnosis.展开更多
Studies have shown that human hair keratin(HHK) has no antigenicity and excellent mechanical properties. Schwann cells, as unique glial cells in the peripheral nervous system, can be induced by interleukin-1β to secr...Studies have shown that human hair keratin(HHK) has no antigenicity and excellent mechanical properties. Schwann cells, as unique glial cells in the peripheral nervous system, can be induced by interleukin-1β to secrete nerve growth factor, which promotes neural regeneration. Therefore, HHK with Schwann cells may be a more effective approach to repair nerve defects than HHK without Schwann cells. In this study, we established an artificial nerve graft by loading an HHK skeleton with activated Schwann cells. We found that the longitudinal HHK microfilament structure provided adhesion medium, space and direction for Schwann cells, and promoted Schwann cell growth and nerve fiber regeneration. In addition, interleukin-1β not only activates Schwann cells, but also strengthens their activity and increases the expression of nerve growth factors. Activated Schwann cells activate macrophages, and activated macrophages secrete interleukin-1β, which maintains the activity of Schwann cells. Thus, a beneficial cycle forms and promotes nerve repair. Furthermore, our studies have found that the newly constructed artificial nerve graft promotes the improvements in nerve conduction function and motor function in rats with sciatic nerve injury, and increases the expression of nerve injury repair factors fibroblast growth factor 2 and human transforming growth factor B receptor 2. These findings suggest that this artificial nerve graft effectively repairs peripheral nerve injury.展开更多
Neuronal networks,especially those in the central nervous system(CNS),evolved to support extensive functional capabilities while ensuring stability.Several physiological"brakes"that maintain the stability of...Neuronal networks,especially those in the central nervous system(CNS),evolved to support extensive functional capabilities while ensuring stability.Several physiological"brakes"that maintain the stability of the neuronal networks in a healthy state quickly become a hinderance postinjury.These"brakes"include inhibition from the extracellular environment,intrinsic factors of neurons and the control of neuronal plasticity.There are distinct differences between the neuronal networks in the peripheral nervous system(PNS)and the CNS.Underpinning these differences is the trade-off between reduced functional capabilities with increased adaptability through the formation of new connections and new neurons.The PNS has"facilitators"that stimulate neuroregeneration and plasticity,while the CNS has"brakes"that limit them.By studying how these"facilitators"and"brakes"work and identifying the key processes and molecules involved,we can attempt to apply these theories to the neuronal networks of the CNS to increase its adaptability.The difference in adaptability between the CNS and PNS leads to a difference in neuroregenerative properties and plasticity.Plasticity ensures quick functional recovery of abilities in the short and medium term.Neuroregeneration involves synthesizing new neurons and connections,providing extra resources in the long term to replace those damaged by the injury,and achieving a lasting functional recovery.Therefore,by understanding the factors that affect neuroregeneration and plasticity,we can combine their advantages and develop rehabilitation techniques.Rehabilitation training methods,coordinated with pharmacological interventions and/or electrical stimulation,contributes to a precise,holistic treatment plan that achieves functional recovery from nervous system injuries.Furthermore,these techniques are not limited to limb movement,as other functions lost as a result of brain injury,such as speech,can also be recovered with an appropriate training program.展开更多
The development,maturation and regeneration of Schwann cells(SCs),the main glial cells of the peripheral nervous system,require the coordinate and complementary interaction among several factors,signals and intracel...The development,maturation and regeneration of Schwann cells(SCs),the main glial cells of the peripheral nervous system,require the coordinate and complementary interaction among several factors,signals and intracellular pathways.These regulatory molecules consist of integrins,neuregulins,growth factors,hormones,neurotransmitters,as well as entire intracellular pathways including protein-kinase A,C,Akt,Erk/MAPK,Hippo,mTOR,etc.For instance,Hippo pathway is overall involved in proliferation,apoptosis,regeneration and organ size control,being crucial in cancer proliferation process.In SCs,Hippo is linked to merlin and YAP/TAZ signaling and it seems to respond to mechanic/physical challenges.Recently,among factors regulating SCs,also the signaling intermediates Src tyrosine kinase and focal adhesion kinase(FAK)proved relevant for SC fate,participating in the regulation of adhesion,motility,migration and in vitro myelination.In SCs,the factors Src and FAK are regulated by the neuroactive steroid allopregnanolone,thus corroborating the importance of this steroid in the control of SC maturation.In this review,we illustrate some old and novel signaling pathways modulating SC biology and functions during the different developmental,mature and regenerative states展开更多
BACKGROUND:Gastrointestinal motility dysfunction in multiple organ dysfunction syndrome (MODS) has been reported to be related to damage to interstitial cells of Cajal (ICC). In the entedc nervous system, ICC and...BACKGROUND:Gastrointestinal motility dysfunction in multiple organ dysfunction syndrome (MODS) has been reported to be related to damage to interstitial cells of Cajal (ICC). In the entedc nervous system, ICC and smooth muscle cells are connected in a network to form a special functional unit. Many gastrointestinal motility dysfunction diseases are associated with damage to this network.OBJECTIVE:To investigate the morphological changes of intestinal ICC, and to explore the mechanisms underlying gastrointestinal motility dysfunction in rats with MODS.DESIGN, TIME AND SE'I-FING:The randomized, controlled, experiment was performed at the Central Laboratory of the First Affiliated Hospital of Dalian Medical University of China between June 2007 and March 2009.MATERIALS:Escherichia coli (E. colistrain O127 H6) and bovine serum albumin were purchased from Sigma, USA.METHODS:A total of 40 Wistar rats were equally and randomly divided into MODS group and control group. Suspension of E. coil strain O127 H6 containing BaSO4 and saline were sterilely injected into the abdominal cavity of rats in the MODS and control groups, respectively.MAIN OUTCOME MEASURES:Immunohistochemical double-staining and confocal laser scanning microscopy were used to observe the morphological changes in intestinal cholinergic nerves and ICC in the deep muscular plexus network. Electron microscopy was employed to evaluate the ultrastructural features of ICC in the deep muscular plexus of rats with MODS.RESULTS:Compared with the control group, the distributions and densities of cholinergic/nitrergic newes and ICC in the deep muscular plexus were significantly decreased in the MODS group (P 〈 0.01). The enteric nerve-ICC network were disrupted.CONCLUSION:There is ultrastructural injury in the ICC in the deep muscular plexus and enteric nerves of the intestine in rats with MODS, which may be associated with the dysmotility of the gastrointestinal tract in MODS.展开更多
Applying a stimulating current to acupoints through acupuncture needles–known as electroacupuncture–has the potential to produce analgesic effects in human subjects and experimental animals. When acupuncture was app...Applying a stimulating current to acupoints through acupuncture needles–known as electroacupuncture–has the potential to produce analgesic effects in human subjects and experimental animals. When acupuncture was applied in a rat model, adenosine 5-triphosphate disodium in the extracellular space was broken down into adenosine, which in turn inhibited pain transmission by means of an adenosine A1 receptor-dependent process. Direct injection of an adenosine A1 receptor agonist enhanced the analgesic effect of acupuncture. The analgesic effect of acupuncture appears to be mediated by activation of A1 receptors located on ascending nerves. In neuropathic pain, there is upregulation of P2X purinoceptor 3 (P2X3) receptor expression in dorsal root ganglion neurons. Conversely, the onset of mechanical hyperalgesia was diminished and established hyperalgesia was significantly reversed when P2X3 receptor expression was downregulated. The pathways upon which electroacupuncture appear to act are interwoven with pain pathways, and electroacupuncture stimuli converge with impulses originating from painful areas. Electroacupuncture may act via purinergic A1 and P2X3 receptors simultaneously to induce an analgesic effect on neuropathic pain.展开更多
基金state assignment 0671-2020-0058 of the Ministry of Education and Science of Russian FederationIIS and GAM were supported by the Russian Foundation for Basic Research grant 18-54-45023 Ind_aKazan Federal University Strategic Academic Leadership Program(to IIS).
文摘The intrinsic ability of peripheral nerves to regenerate after injury is extremely limited,especially in case of severe injury.This often leads to poor motor function and permanent disability.Existing approaches for the treatment of injured nerves do not provide appropriate conditions to support survival and growth of nerve cells.This drawback can be compensated by the use of gene therapy and cell therapy-based drugs that locally provide an increase in the key regulators of nerve growth,including neurotrophic factors and extracellular matrix proteins.Each growth factor plays its own specific angiotrophic or neurotrophic role.Currently,growth factors are widely studied as accelerators of nerve regeneration.Particularly noteworthy is synergy between various growth factors,that is essential for both angiogenesis and neurogenesis.Fibroblast growth factor 2 and vascular endothelial growth factor are widely known for their proangiogenic effects.At the same time,fibroblast growth factor 2 and vascular endothelial growth factor stimulate neural cell growth and play an important role in neurodegenerative diseases of the peripheral nervous system.Taken together,their neurotrophic and angiogenic properties have positive effect on the regeneration process.In this review we provide an in-depth overview of the role of fibroblast growth factor 2 and vascular endothelial growth factor in the regeneration of peripheral nerves,thus demonstrating their neurotherapeutic efficacy in improving neuron survival in the peripheral nervous system.
基金supported by grants from the National Program on Key Basic Research Project of China(973 Program),No.2014CB542206the National Natural Science Foundation of China,No.81201389,30973052Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China,No.IRT13051
文摘Neuregulin-1 type Ⅲ is a key regulator in Schwann cell proliferation, committing to a myelinat- ing fate and regulating myelin sheath thickness. However, the expression pattern of neuregulin- 1 type III in the peripheral nervous system during developmental periods (such as the premyelin- ating stage, myelinating stage and postmyelinating stage) has rarely been studied. In this study, dorsal root ganglia were isolated from rats between postnatal day 1 and postnatal day 56. The expression pattern of neuregulin-1 type III in dorsal root ganglia neurons at various develop- mental stages were compared by quantitative real-time polymerase chain reaction, western blot assay and immunofluorescent staining. The expression of neuregulin-I type Ⅲ mRNA reached its peak at postnatal day 3 and then stabilized at a relative high expression level from postnatal day 3 to postnatal day 56. The expression of neuregulin-1 type III protein increased gradually from postnatal day 1, reached a peak at postnatal day 28, and then decreased at postnatal day 56. Immunofluorescent staining results showed a similar tendency to western blot assay results. Experimental findings indicate that the expression of neuregulin-1 type III in rat dorsal root ganglion was increased during the premyelinating (from postnatal day 2 to postnatal day 5) and myelinating stage (from postnatal day 5 to postnatal day 10), but remained at a high level in the postmyelinating stage (after postnatal day 10).
文摘Cerebrolysin is a drug consisting of low-molecular-weight neurotrophic peptides and free amino acids. Cerebrolysin has been shown to ameliorate the effects of oxidative stress, reduce apoptosis, and promote neuronal growth in several degenerative and acquired central nervous system insults, including dementias, stroke, and traumatic injuries. Little is known about its therapeutic efficacy in peripheral nervous system diseases. In this study, we clinically evaluated the effects of cerebrolysin on peripheral nervous system lesions. We evaluated the clinical efficacy of cerebrolysin in six patients with the following conditions who failed to respond to conventional therapies: (1) atonic bladder due to inflammatory radiculitis; (2) paraplegia due to inflammatory radiculoneuropathy; (3) post-traumatic brachial plexopathy; (4) compressive radial nerve injury; (5) post-traumatic facial nerve paralysis; and (6) diabetic ophthalmoplegia. Our results showed that cerebrolysin was more associated with rapid neurological recovery after various peripheral nerve lesions than other therapies including steroids and supportive therapies such as vitamins and antioxidants. The present results support the therapeutic efficacy of cerebrolysin in the treatment of acquired peripheral nervous system diseases.
文摘Most researchers believe that neurogenesis in mature mammals is restricted only to the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricle in the central nervous system. In the peripheral nervous system, neurogenesis is thought to be active only during prenatal development, with the exception of the olfactory neuroepithelium. However, sensory ganglia in the adult peripheral nervous system have been reported to contain precursor cells that can proliferate in vitro and be induced to differentiate into neurons. The occurrence of insult-induced neurogenesis, which has been reported by several investigators in the brain, is limited to a few recent reports for the peripheral nervous system. These reports suggest that damage to the adult nervous system induces mechanisms similar to those that control the generation of new neurons during prenatal development. Understanding conditions under which neurogenesis can be induced in physiologically non-neurogenic regions in adults is one of the major challenges for developing therapeutic strategies to repair neurological damage. However, the induced neurogenesis in the peripheral nervous system is still largely unexplored. This review presents the history of research on adult neurogenesis in the peripheral nervous system, which dates back more than 100 years and reveals the evidence on the under estimated potential for generation of new neurons in the adult peripheral nervous system.
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 Ministry of Education and Science of Russia grants 6.4951.2017/6.7 and 6.6З24.2017/8.9
文摘Traumatic cerebral or spinal cord injury induced by military,traffic,and sports accidents,falls or environmental and anthropogenic catastrophes are among main causes of people mortality and disability,especially in young and middle age men(Kobeissy,2015).Axon transection,or axotomy,occurs in wounds and during surgery.
基金Institute for Basic Science,Grant/Award Number:IBS-R026-D1Korea Medical Device Development Fund,Grant/Award Number:RMS 2022-11-1209/KMDF RS-2022-00141392+1 种基金National Research Foundation of Korea,Grant/Award Numbers:2020R1A5A1019131,2021M3D1A2049914,2022R1A5A6000846,2023R1A2C2006257Korea Evaluation Institute of Industrial Technology,Grant/Award Number:20013621。
文摘The peripheral nervous system(PNS)is a fascinatingly complex and crucial component of the human body,responsible for transmitting vital signals throughout the body's intricate network of nerves.Its efficient functioning is paramount to our health,with any dysfunction often resulting in serious medical conditions,including motor disorders,neurological diseases,and psychiatric disorders.Recent strides in science and technology have made neuromodulation of the PNS a promising avenue for addressing these health issues.Neuromodulation involves modifying nerve activity using a range of techniques,such as electrical,chemical,optical,and mechanical stimulation.Bioelectronics plays a critical role in this effort,allowing for precise,controlled,and sustained stimulation of the PNS.This paper provides an overview of the PNS,discusses the current state of neuromodulation devices,and presents emerging trends in the field,including advances in wireless power transfer and materials,that are shaping the future of neuromodulation.
基金supported by grants from the Natural Science Foundation of Tianjin(General Program),Nos.23JCYBJC01390(to RL),22JCYBJC00220(to XC),and 22JCYBJC00210(to QL).
文摘Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities.Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites,neglecting multilevel pathological analysis of the overall nervous system and target organs.This has led to restrictions on current therapeutic approaches.In this paper,we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective,covering the central nervous system,peripheral nervous system,and target organs.After peripheral nerve injury,the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves;changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord.The nerve will undergo axonal regeneration,activation of Schwann cells,inflammatory response,and vascular system regeneration at the injury site.Corresponding damage to target organs can occur,including skeletal muscle atrophy and sensory receptor disruption.We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury.The main current treatments are conducted passively and include physical factor rehabilitation,pharmacological treatments,cell-based therapies,and physical exercise.However,most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway.Therefore,we should further explore multilevel treatment options that produce effective,long-lasting results,perhaps requiring a combination of passive(traditional)and active(novel)treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.
基金supported by the National Natural Science Foundation of China,No. 82071374Discipline Construction Project of Guangdong Medical University,Nos. 1.13 and 4.1.19+1 种基金College Students Innovative Experimental Project in Guangdong Medical University,Nos. FYDB015, ZCDS001, ZYDB004, ZYDB016, and ZZDI001College Students’ Science and Technology Innovation Training Project,Nos. GDMU2020194, GDMU2020195, GDMU2021021, GDMU2021023, GDMU2021091, GDMU2021111 (all to HFW)。
文摘Vimentin is a major type Ⅲ intermediate filament protein that plays important roles in several basic cellular functions including cell migration, proliferation, and division. Although vimentin is a cytoplasmic protein, it also exists in the extracellular matrix and at the cell surface. Previous studies have shown that vimentin may exert multiple physiological effects in different nervous system injuries and diseases. For example, the studies of vimentin in spinal cord injury and stroke mainly focus on the formation of reactive astrocytes. Reduced glial scar, increased axonal regeneration, and improved motor function have been noted after spinal cord injury in vimentin and glial fibrillary acidic protein knockout(GFAPVIM) mice. However, attenuated glial scar formation in post-stroke in GFAP–/– VIM–/– mice resulted in abnormal neuronal network restoration and worse neurological recovery. These opposite results have been attributed to the multiple roles of glial scar in different temporal and spatial conditions. In addition, extracellular vimentin may be a neurotrophic factor that promotes axonal extension by interaction with the insulin-like growth factor 1 receptor. In the pathogenesis of bacterial meningitis, cell surface vimentin is a meningitis facilitator, acting as a receptor of multiple pathogenic bacteria, including E. coli K1, Listeria monocytogenes, and group B streptococcus. Compared with wild type mice, VIMmice are less susceptible to bacterial infection and exhibit a reduced inflammatory response, suggesting that vimentin is necessary to induce the pathogenesis of meningitis. Recently published literature showed that vimentin serves as a double-edged sword in the nervous system, regulating axonal regrowth, myelination, apoptosis, and neuroinflammation. This review aims to provide an overview of vimentin in spinal cord injury, stroke, bacterial meningitis, gliomas, and peripheral nerve injury and to discuss the potential therapeutic methods involving vimentin manipulation in improving axonal regeneration, alleviating infection, inhibiting brain tumor progression, and enhancing nerve myelination.
基金supported by the National Natural Science Foundation of China,No.81171178the Natural Science Foundation of Shanxi Province in China,No.2012011036-3the Research Project of Shanxi Scholarship Council of China,No.2012-047
文摘Paired immunoglobulin-like receptor B(Pir B) is a functional receptor of myelin-associated inhibitors for axonal regeneration and synaptic plasticity in the central nervous system, and thus suppresses nerve regeneration. The regulatory effect of Pir B on injured nerves has received a lot of attention. To better understand nerve regeneration inability after spinal cord injury, this study aimed to investigate the distribution of Pir B(via immunofluorescence) in the central nervous system and peripheral nervous system 10 days after injury. Immunoreactivity for Pir B increased in the dorsal root ganglia, sciatic nerves, and spinal cord segments. In the dorsal root ganglia and sciatic nerves, Pir B was mainly distributed along neuronal and axonal membranes. Pir B was found to exhibit a diffuse, intricate distribution in the dorsal and ventral regions. Immunoreactivity for Pir B was enhanced in some cortical neurons located in the bilateral precentral gyri. Overall, the findings suggest a pattern of Pir B immunoreactivity in the nervous system after unilateral spinal transection injury, and also indicate that Pir B may suppress repair after injury.
基金supported by the National Natural Science Foundation of China,No.81130080,31300942the National Key Basic Research Program of China(973 Program)+5 种基金No.2014CB542202the Natural Science Foundation of Jiangsu Province,China,No.BK20150409the Natural Science Foundation of Jiangsu Higher Education Institutions of China,No.15KJB180013the Scientific Research Foundation of Nantong University of China,No.14R29the Natural Science Foundation of Nantong City in China,No.MS12015043the Priority Academic Program Development of Jiangsu Higher Education Institutions of China
文摘Tau, a primary component of microtubule-associated protein, promotes microtubule assembly and/or disassembly and maintains the stability of the microtubule structure. Although the importance of tau in neurodegenerative diseases has been well demonstrated, wheth- er tau is involved in peripheral nerve regeneration remains unknown. In the current study, we obtained sciatic nerve tissue from adult rats 0, 1, 4, 7, and 14 days after sciatic nerve crush and examined tau mRNA and protein expression levels and the location of tau in the sciatic nerve following peripheral nerve injury. The results from our quantitative reverse transcription polymerase chain reaction analysis showed that compared with the uninjured control sciatic nerve, mRNA expression levels for both tau and tau tubulin kinase 1, a serine/ threonine kinase that regulates tau phosphorylation, were decreased following peripheral nerve injury. Our western blot assay results suggested that the protein expression levels of tau and phosphorylated tau initially decreased 1 day post nerve injury but then gradually increased. The results of our immunohistochemical labeling showed that the location of tau protein was not altered by nerve injury. Thus, these results showed that the expression of tau was changed following sciatic nerve crush, suggesting that tau may be involved in periph- eral nerve repair and regeneration.
基金supported by the National Key Research and Development Program of China,No.2017YFA0104703(to FD)the National Natural Science Foundation of China(Major Program),No.92068112(to FD)+2 种基金Science and Technology Program of Nantong of China,No.JC2020035(to QRH)National Natural Science Foundation of China,Nos.31500927(to QRH)and 31870977(to HYS)the Priority Academic Program Development of Jiangsu High Education Institutions(PAPD)(to FD).
文摘Peripheral nerve fibroblasts play a critical role in nerve development and regeneration.Our previous study found that peripheral nerve fibroblasts have different sensory and motor phenotypes.Fibroblasts of different phenotypes can guide the migration of Schwann cells to the same sensory or motor phenotype.In this study,we analyzed the different effects of peripheral nerve-derived fibroblasts and cardiac fibroblasts on motoneurons.Compared with cardiac fibroblasts,peripheral nerve fibroblasts greatly promoted motoneuron neurite outgrowth.Transcriptome analysis results identified 491 genes that were differentially expressed in peripheral nerve fibroblasts and cardiac fibroblasts.Among these,130 were significantly upregulated in peripheral nerve fibroblasts compared with cardiac fibroblasts.These genes may be involved in axon guidance and neuron projection.Three days after sciatic nerve transection in rats,peripheral nerve fibroblasts accumulated in the proximal and distal nerve stumps,and most expressed brain-derived neurotrophic factor.In vitro,brain-derived neurotrophic factor secreted from peripheral nerve fibroblasts increased the expression ofβ-actin and F-actin through the extracellular regulated protein kinase and serine/threonine kinase pathways,and enhanced motoneuron neurite outgrowth.These findings suggest that peripheral nerve fibroblasts and cardiac fibroblasts exhibit different patterns of gene expression.Peripheral nerve fibroblasts can promote motoneuron neurite outgrowth.
基金University of Wyoming Startup funds,United States Department of Defense,No. W81XWH-17-1-0402 (to JSB)the University of Wyoming Sensory Biology COBRE under National Institutes of Health (NIH),No. 5P20GM121310-02 (to JSB)+2 种基金the National Institute of General Medical Sciences of the NIH,No. P20GM103432 (to JSB)DOD AFIRM III,No. W81XWH-20-2-0029 (to GDB)a Lone Star Paralysis Foundation gi?t (to GDB)。
文摘The peripheral nervous system has an extensive branching organization, and peripheral nerve injuries that ablate branch points present a complex challenge for clinical repair. Ablations of linear segments of the PNS have been extensively studied and routinely treated with autografts, acellular nerve allografts, conduits, wraps, and nerve transfers. In contrast, segmental-loss peripheral nerve injuries, in which one or more branch points are ablated so that there are three or more nerve endings, present additional complications that have not been rigorously studied or documented. This review discusses:(1) the branched anatomy of the peripheral nervous system,(2) case reports describing how peripheral nerve injuries with branched ablations have been surgically managed,(3) factors known to influence regeneration through branched nerve structures,(4) techniques and models of branched peripheral nerve injuries in animal models, and(5) conclusions regarding outcome measures and studies needed to improve understanding of regeneration through ablated branched structures of the peripheral nervous system.
基金supported by San Paolo Bank Foundation and Piemonte Region
文摘It is today widely acknowledged that nerve repair is now more than a matter of perfect microsurgical reconstruction only and that, to further improve clinical outcome, the involvement of different scientific disciplines is required. This evolving reconstructive/regenerative approach is based on the interdisciplinary and integrated pillars of tissue engineering such as reconstructive microsurgery, transplantation and biomaterials. In this paper, some of the most promising innovations for the tissue engineering of nerves, emerging from basic science investigation, are critically overviewed with special focus on those approaches that appear today to be more suitable for clinical translation.
文摘BACKGROUND Vasculitis,a systemic disorder with inflammation of blood vessel walls,can develop broad spectrum of signs and symptoms according to involvement of various organs,and therefore,early diagnosis of vasculitis is challenging.We herein describe a patient who developed a special case of systemic vasculitis with mononeuropathy multiplex,rectal perforation and antiphospholipid syndrome(APS)presented with pulmonary embolism.CASE SUMMARY A 61-year-old woman visited hospital with complaints of myalgia and occasional fever.She was initially diagnosed as proctitis and treated with antibiotics,however,there was no improvement.In addition,she also complained right foot drop with hypesthesia,and left 2^(nd) and 3^(rd) finger tingling sensation.She underwent nerve conduction study for evaluation,and it revealed sensorimotor polyneuropathy in the left arm and bilateral legs.Subsequent sural nerve biopsy strongly suggested vasculitic neuropathy.Based on nerve biopsy and clinical manifestation,she was diagnosed with vasculitis and treated with immunosuppressive therapy.During treatment,sudden rectal perforation and pulmonary thromboembolism occurred,and further laboratory study suggested probable concomitant APS.Emergency Hartmann operation was performed for rectal perforation,and anti-coagulation therapy was started for APS.After few cycles of immunosuppressive therapy,tingling sensation and weakness in her hand and foot had been partially recovered and vasculitis was considered to be stationary.CONCLUSION Vasculitis can be presented with a variety of signs and symptoms,therefore,clinicians should always consider the possibility of diagnosis.
基金supported by Military Medical Science&Technology Youth Training Program,No. 19QNP005President Foundation of Nanfang Hospital,Southern Medical University,No. 2020B028 (both to JY)。
文摘Studies have shown that human hair keratin(HHK) has no antigenicity and excellent mechanical properties. Schwann cells, as unique glial cells in the peripheral nervous system, can be induced by interleukin-1β to secrete nerve growth factor, which promotes neural regeneration. Therefore, HHK with Schwann cells may be a more effective approach to repair nerve defects than HHK without Schwann cells. In this study, we established an artificial nerve graft by loading an HHK skeleton with activated Schwann cells. We found that the longitudinal HHK microfilament structure provided adhesion medium, space and direction for Schwann cells, and promoted Schwann cell growth and nerve fiber regeneration. In addition, interleukin-1β not only activates Schwann cells, but also strengthens their activity and increases the expression of nerve growth factors. Activated Schwann cells activate macrophages, and activated macrophages secrete interleukin-1β, which maintains the activity of Schwann cells. Thus, a beneficial cycle forms and promotes nerve repair. Furthermore, our studies have found that the newly constructed artificial nerve graft promotes the improvements in nerve conduction function and motor function in rats with sciatic nerve injury, and increases the expression of nerve injury repair factors fibroblast growth factor 2 and human transforming growth factor B receptor 2. These findings suggest that this artificial nerve graft effectively repairs peripheral nerve injury.
文摘Neuronal networks,especially those in the central nervous system(CNS),evolved to support extensive functional capabilities while ensuring stability.Several physiological"brakes"that maintain the stability of the neuronal networks in a healthy state quickly become a hinderance postinjury.These"brakes"include inhibition from the extracellular environment,intrinsic factors of neurons and the control of neuronal plasticity.There are distinct differences between the neuronal networks in the peripheral nervous system(PNS)and the CNS.Underpinning these differences is the trade-off between reduced functional capabilities with increased adaptability through the formation of new connections and new neurons.The PNS has"facilitators"that stimulate neuroregeneration and plasticity,while the CNS has"brakes"that limit them.By studying how these"facilitators"and"brakes"work and identifying the key processes and molecules involved,we can attempt to apply these theories to the neuronal networks of the CNS to increase its adaptability.The difference in adaptability between the CNS and PNS leads to a difference in neuroregenerative properties and plasticity.Plasticity ensures quick functional recovery of abilities in the short and medium term.Neuroregeneration involves synthesizing new neurons and connections,providing extra resources in the long term to replace those damaged by the injury,and achieving a lasting functional recovery.Therefore,by understanding the factors that affect neuroregeneration and plasticity,we can combine their advantages and develop rehabilitation techniques.Rehabilitation training methods,coordinated with pharmacological interventions and/or electrical stimulation,contributes to a precise,holistic treatment plan that achieves functional recovery from nervous system injuries.Furthermore,these techniques are not limited to limb movement,as other functions lost as a result of brain injury,such as speech,can also be recovered with an appropriate training program.
基金Financial support by University of Milan,institutional funding "Piano di sostegno per la ricerca 2016-Linea 2 Azione B"
文摘The development,maturation and regeneration of Schwann cells(SCs),the main glial cells of the peripheral nervous system,require the coordinate and complementary interaction among several factors,signals and intracellular pathways.These regulatory molecules consist of integrins,neuregulins,growth factors,hormones,neurotransmitters,as well as entire intracellular pathways including protein-kinase A,C,Akt,Erk/MAPK,Hippo,mTOR,etc.For instance,Hippo pathway is overall involved in proliferation,apoptosis,regeneration and organ size control,being crucial in cancer proliferation process.In SCs,Hippo is linked to merlin and YAP/TAZ signaling and it seems to respond to mechanic/physical challenges.Recently,among factors regulating SCs,also the signaling intermediates Src tyrosine kinase and focal adhesion kinase(FAK)proved relevant for SC fate,participating in the regulation of adhesion,motility,migration and in vitro myelination.In SCs,the factors Src and FAK are regulated by the neuroactive steroid allopregnanolone,thus corroborating the importance of this steroid in the control of SC maturation.In this review,we illustrate some old and novel signaling pathways modulating SC biology and functions during the different developmental,mature and regenerative states
基金Supported by the National Natural Science Foundation of China,No. 30772860
文摘BACKGROUND:Gastrointestinal motility dysfunction in multiple organ dysfunction syndrome (MODS) has been reported to be related to damage to interstitial cells of Cajal (ICC). In the entedc nervous system, ICC and smooth muscle cells are connected in a network to form a special functional unit. Many gastrointestinal motility dysfunction diseases are associated with damage to this network.OBJECTIVE:To investigate the morphological changes of intestinal ICC, and to explore the mechanisms underlying gastrointestinal motility dysfunction in rats with MODS.DESIGN, TIME AND SE'I-FING:The randomized, controlled, experiment was performed at the Central Laboratory of the First Affiliated Hospital of Dalian Medical University of China between June 2007 and March 2009.MATERIALS:Escherichia coli (E. colistrain O127 H6) and bovine serum albumin were purchased from Sigma, USA.METHODS:A total of 40 Wistar rats were equally and randomly divided into MODS group and control group. Suspension of E. coil strain O127 H6 containing BaSO4 and saline were sterilely injected into the abdominal cavity of rats in the MODS and control groups, respectively.MAIN OUTCOME MEASURES:Immunohistochemical double-staining and confocal laser scanning microscopy were used to observe the morphological changes in intestinal cholinergic nerves and ICC in the deep muscular plexus network. Electron microscopy was employed to evaluate the ultrastructural features of ICC in the deep muscular plexus of rats with MODS.RESULTS:Compared with the control group, the distributions and densities of cholinergic/nitrergic newes and ICC in the deep muscular plexus were significantly decreased in the MODS group (P 〈 0.01). The enteric nerve-ICC network were disrupted.CONCLUSION:There is ultrastructural injury in the ICC in the deep muscular plexus and enteric nerves of the intestine in rats with MODS, which may be associated with the dysmotility of the gastrointestinal tract in MODS.
文摘Applying a stimulating current to acupoints through acupuncture needles–known as electroacupuncture–has the potential to produce analgesic effects in human subjects and experimental animals. When acupuncture was applied in a rat model, adenosine 5-triphosphate disodium in the extracellular space was broken down into adenosine, which in turn inhibited pain transmission by means of an adenosine A1 receptor-dependent process. Direct injection of an adenosine A1 receptor agonist enhanced the analgesic effect of acupuncture. The analgesic effect of acupuncture appears to be mediated by activation of A1 receptors located on ascending nerves. In neuropathic pain, there is upregulation of P2X purinoceptor 3 (P2X3) receptor expression in dorsal root ganglion neurons. Conversely, the onset of mechanical hyperalgesia was diminished and established hyperalgesia was significantly reversed when P2X3 receptor expression was downregulated. The pathways upon which electroacupuncture appear to act are interwoven with pain pathways, and electroacupuncture stimuli converge with impulses originating from painful areas. Electroacupuncture may act via purinergic A1 and P2X3 receptors simultaneously to induce an analgesic effect on neuropathic pain.