Spinal cord injury represents a devastating central nervous system injury that could impair the mobility and sensory function of afflicted patients.The hallmarks of spinal cord injury include neuroinflammation,axonal ...Spinal cord injury represents a devastating central nervous system injury that could impair the mobility and sensory function of afflicted patients.The hallmarks of spinal cord injury include neuroinflammation,axonal degeneration,neuronal loss,and reactive gliosis.Furthermore,the formation of a glial scar at the injury site elicits an inhibitory environment for potential neuroregeneration.Besides axonal regeneration,a significant challenge in treating spinal cord injury is to replenish the neurons lost during the pathological process.However,despite decades of research efforts,current strategies including stem cell transplantation have not resulted in a successful clinical therapy.Furthermore,stem cell transplantation faces serious hurdles such as immunorejection of the transplanted cells and ethical issues.In vivo neuronal reprogramming is a recently developed technology and leading a major breakthrough in regenerative medicine.This innovative technology converts endogenous glial cells into functional neurons for injury repair in the central nervous system.The feasibility of in vivo neuronal reprogramming has been demonstrated successfully in models of different neurological disorders including spinal cord injury by numerous laboratories.Several reprogramming factors,mainly the pro-neural transcription factors,have been utilized to reprogram endogenous glial cells into functional neurons with distinct phenotypes.So far,the literature on in vivo neuronal reprogramming in the model of spinal cord injury is still small.In this review,we summarize a limited number of such reports and discuss several questions that we think are important for applying in vivo neuronal reprogramming in the research field of spinal cord injury as well as other central nervous system disorders.展开更多
In this review, we outline the major neural plasticity mechanisms that have been identified in the adult central nervous system （CNS）, and offer a perspective on how they regulate CNS function. In particular we exam...In this review, we outline the major neural plasticity mechanisms that have been identified in the adult central nervous system （CNS）, and offer a perspective on how they regulate CNS function. In particular we examine how myelin plasticity can operate alongside neurogenesis and synaptic plasticity to influence information processing and transfer in the mature CNS.展开更多
Regenerative approaches towards neuronal loss following traumatic brain or spinal cord injury have long been considered a dogma in neuroscience and remain a cutting-edge area of research.This is reflected in a large d...Regenerative approaches towards neuronal loss following traumatic brain or spinal cord injury have long been considered a dogma in neuroscience and remain a cutting-edge area of research.This is reflected in a large disparity between the number of studies investigating primary and secondary injury as therapeutic to rgets in spinal co rd and traumatic brain injuries.Significant advances in biotechnology may have the potential to reshape the current state-of-the-art and bring focus to primary injury neurotrauma research.Recent studies using neural-glial factor/antigen 2(NG2)cells indicate that they may differentiate into neurons even in the developed brain.As these cells show great potential to play a regenerative role,studies have been conducted to test various manipulations in neurotrauma models aimed at eliciting a neurogenic response from them.In the present study,we systematically reviewed the experimental protocols and findings described in the scientific literature,which were peer-reviewed original research articles(1)describing preclinical experimental studies,(2)investigating NG2 cells,(3)associated with neurogenesis and neurotrauma,and(4)in vitro and/or in vivo,available in PubMed/MEDLINE,Web of Science or SCOPUS,from 1998 to 2022.Here,we have reviewed a total of 1504 papers,and summarized findings that ultimately suggest that NG2 cells possess an inducible neurogenic potential in animal models and in vitro.We also discriminate findings of NG2 neurogenesis promoted by different pharmacological and genetic approaches over functional and biochemical outcomes of traumatic brain injury and spinal co rd injury models,and provide mounting evidence for the potential benefits of manipulated NG2 cell ex vivo transplantation in primary injury treatment.These findings indicate the feasibility of NG2 cell neurogenesis strategies and add new players in the development of therapeutic alternatives for neurotrauma.展开更多
Cerebral small vessel disease(CSVD)is one of the most prevalent pathologic processes affecting 5%of people over 50 years of age and contributing to 45%of dementia cases.Increasing evidence has demonstrated the patholo...Cerebral small vessel disease(CSVD)is one of the most prevalent pathologic processes affecting 5%of people over 50 years of age and contributing to 45%of dementia cases.Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion,impaired cerebral vascular reactivity,and leakage of the blood–brain barrier in CSVD.However,the pathogenesis of CSVD remains elusive thus far,and no radical treatment has been developed.NG2 glia,also known as oligodendrocyte precursor cells,are the fourth type of glial cell in addition to astrocytes,microglia,and oligodendrocytes in the mammalian central nervous system.Many novel functions for NG2 glia in physiological and pathological states have recently been revealed.In this review,we discuss the role of NG2 glia in CSVD and the underlying mechanisms.展开更多
Oligodendrocyte precursor cells(OPCs)and microglia are two very fascinating cell types with a multitude of important but different functions.At a first glance,they appear not to share many cellular properties,nor are ...Oligodendrocyte precursor cells(OPCs)and microglia are two very fascinating cell types with a multitude of important but different functions.At a first glance,they appear not to share many cellular properties,nor are directly related to one another or derived from a common ancestor.Despite all differences,emerging data show that both cell types express the protein nerve/glial antigen 2(NG2)after pathological insults(Figure 1).For years,it remained controversial whether microglia really could express NG2 upon injury,with contradictory results reported among different disease models.Addressing this question,we could recently show by using triple transgenic knock-in mice and either an acute injury model(stab wound injury)or the middle cerebral artery occlusion combined with immunohistochemistry that a subset of microglia activates the cspg4 gene in a disease dependent manner leading to a bonafide microglia-specific NG2 protein expression besides OPCs and pericytes.Our data show that the cspg4 gene not only gets transcribed in microglia based on reporter expression after recombination,but also the protein itself is expressed(Huang et al.,2020).展开更多
Previous studies have demonstrated that melatonin combined with exercise can alleviate secondary damage after spinal cord injury in rats. Therefore, it is hypothesized that melatonin combined with exercise can also al...Previous studies have demonstrated that melatonin combined with exercise can alleviate secondary damage after spinal cord injury in rats. Therefore, it is hypothesized that melatonin combined with exercise can also alleviate ischemic brain damage. In this study, adult rats were subjected to right middle cerebral artery occlusion after receiving 10 mg/kg melatonin or vehicle subcutaneously twice daily for 14 days. Forced exercise using an animal treadmill was performed at 20 m/min for 30 minutes per day for 6 days prior to middle cerebral artery occlusion. After middle cerebral artery occlusion, each rat received melatonin combined with exercise, melatonin or exercise alone equally for 7 days until sacrifice. Interestingly, rats receiving melatonin combined with exercise exhibited more severe neurological deficits than those receiving melatonin or exercise alone. Hypoxia-inducible factor la mRNA in the brain tissue was upregulated in rats receiving melatonin combined with exercise. Similarly, microtubule associated protein-2 mRNA expression was significantly upregulated in rats receiving melatonin alone. Chondroitin sulfate proteoglycan 4 （NG2） mRNA expression was significantly decreased in rats receiving melatonin combined with exercise as well as in rats receiving exercise alone. Furthermore, neural cell loss in the primary motor cortex was significantly reduced in rats receiving melatonin or exercise alone, but the change was not observed in rats receiving melatonin combined with exercise. These findings suggest that excessive intervention with melatonin, exercise or their combination may lead to negative effects on ischemia/reperfusion-induced brain damage.展开更多
Polydendrocytes （NG2 cells） are a distinct type of glia that populate the developing and adult central nervous systems （CNS）. In the adult CNS, they retain mitotic activity and represent the largest proliferating ...Polydendrocytes （NG2 cells） are a distinct type of glia that populate the developing and adult central nervous systems （CNS）. In the adult CNS, they retain mitotic activity and represent the largest proliferating cell popula- tion. Genetic and epigenetic mechanisms regulate the fate of polydendrocytes, which give rise to both oligo- dendrocytes and astrocytes. In addition, polydendrocytes actively differentiate into myelin-forming oligodendro- cytes in response to demyelination. This review summarizes the current knowledge regarding polydendrocyte development, which provides an important basis for understanding the mechanisms that lead to the remyelina- tion of demyelinated lesions.展开更多
Cellular therapies are becoming a major focus for the treatment of demyelinating diseases such as multiple sclerosis （MS）, therefore it is important to identify the most effective cell types that promote myelin repa...Cellular therapies are becoming a major focus for the treatment of demyelinating diseases such as multiple sclerosis （MS）, therefore it is important to identify the most effective cell types that promote myelin repair. Several components contribute to the relative benefits of specific cell types including the overall efficacy of the cell therapy, the reproducibility of treatment, the mechanisms of action of distinct cell types and the ease of isolation and generation of therapeutic populations. A range of distinct cell populations promote functional recovery in animal models of MS including neural stem cells and mesenchymal stem cells derived from different tissues. Each of these cell populations has advantages and disadvantages and likely works through distinct mechanisms. The relevance of such mechanisms to myelin repair in the adult central nervous system is unclear since the therapeutic cells are generally derived from developing animals. Here we describe the isolation and characterization of a population of neural cells from the adult spinal cord that are characterized by the expression of the cell surface glycoprotein NG2. In functional studies, injection of adult NG2~ cells into mice with ongoing MOG3~_~5-induced experimental autoimmune encephalomyelitis （EAE） enhanced remyelination in the CNS while the number of CD3＋ T cells in areas of spinal cord demyelination was reduced approximately three-fold. In vivostudies indicated that in EAE, NG2＊ cells stimulated endogenous repair while in vitro they responded to signals in areas of induced inflammation by differentiating into oligodendrocytes. These results suggested that adult NG2~ cells represent a useful cell population for promoting neural repair in a variety of different conditions including demyelinating diseases such as MS.展开更多
Have you heard of NG2 cells or NG2 glia or polydendro- cytes~. These are new names for the precursor cells that used to be referred to as oligodendrocyte precursor cells （OPCs）, which become the oligodendrocytes tha...Have you heard of NG2 cells or NG2 glia or polydendro- cytes~. These are new names for the precursor cells that used to be referred to as oligodendrocyte precursor cells （OPCs）, which become the oligodendrocytes that myelinate central nervous system （CNS） axons. Evidence suggests, however, that they have other functions, besides differentiating into oligodendrocytes. Most notably, the OPCs/NG2 cells are uni- formly distributed in grey matter as well as in white matter, which matches poorly with the distribution of myelinating oligodendrocytes. Furthermore, not every NG2 cell is fated to become an oligodendrocyte. Hence the term OPC can be fairly applied only when discussing the role of these cells in the oligodendrocyte lineage.展开更多
Rat models of T10 spinal cord injury were established with a clamp method. NG2 expression was detected with immunohistochemical staining and western blot. Ten days after spinal cord injury, the number of NG2-positive ...Rat models of T10 spinal cord injury were established with a clamp method. NG2 expression was detected with immunohistochemical staining and western blot. Ten days after spinal cord injury, the number of NG2-positive cells in the damaged areas and NG2 absorbance were both significantly increased. The findings indicate that acute T10 spinal cord injury in rats can lead to upregulation of NG2 protein expression in damaged areas.展开更多
基金supported by startup funds from Medical College of Georgia at Augusta University(to HL)National Institutes of Health R01NS117918,R21NS104394,and R21NS119732(to HL)。
文摘Spinal cord injury represents a devastating central nervous system injury that could impair the mobility and sensory function of afflicted patients.The hallmarks of spinal cord injury include neuroinflammation,axonal degeneration,neuronal loss,and reactive gliosis.Furthermore,the formation of a glial scar at the injury site elicits an inhibitory environment for potential neuroregeneration.Besides axonal regeneration,a significant challenge in treating spinal cord injury is to replenish the neurons lost during the pathological process.However,despite decades of research efforts,current strategies including stem cell transplantation have not resulted in a successful clinical therapy.Furthermore,stem cell transplantation faces serious hurdles such as immunorejection of the transplanted cells and ethical issues.In vivo neuronal reprogramming is a recently developed technology and leading a major breakthrough in regenerative medicine.This innovative technology converts endogenous glial cells into functional neurons for injury repair in the central nervous system.The feasibility of in vivo neuronal reprogramming has been demonstrated successfully in models of different neurological disorders including spinal cord injury by numerous laboratories.Several reprogramming factors,mainly the pro-neural transcription factors,have been utilized to reprogram endogenous glial cells into functional neurons with distinct phenotypes.So far,the literature on in vivo neuronal reprogramming in the model of spinal cord injury is still small.In this review,we summarize a limited number of such reports and discuss several questions that we think are important for applying in vivo neuronal reprogramming in the research field of spinal cord injury as well as other central nervous system disorders.
基金supported by the Australian National Health and Medical Research Council
文摘In this review, we outline the major neural plasticity mechanisms that have been identified in the adult central nervous system （CNS）, and offer a perspective on how they regulate CNS function. In particular we examine how myelin plasticity can operate alongside neurogenesis and synaptic plasticity to influence information processing and transfer in the mature CNS.
基金supported by funding from FAPERGS under Grant No.1010267FAPERGS/PPSUS+8 种基金No.17/2551-0001FAPERGS/PRONEXNo.16/2551-0000499-4FAPERGS/CAPES under Grant No.19/25510000717-5Conselho Nacional de Desenvolvimento Científico e Tecnologico under Grants Nos.4011645/2012-6 and#5465346/2014-6Irish Research Council Government of Ireland Postdoctoral FellowshipNo.GOIPD/2022/792Irish Research Council Enterprise Postdoctoral FellowshipNo.EPSPD/2022/112。
文摘Regenerative approaches towards neuronal loss following traumatic brain or spinal cord injury have long been considered a dogma in neuroscience and remain a cutting-edge area of research.This is reflected in a large disparity between the number of studies investigating primary and secondary injury as therapeutic to rgets in spinal co rd and traumatic brain injuries.Significant advances in biotechnology may have the potential to reshape the current state-of-the-art and bring focus to primary injury neurotrauma research.Recent studies using neural-glial factor/antigen 2(NG2)cells indicate that they may differentiate into neurons even in the developed brain.As these cells show great potential to play a regenerative role,studies have been conducted to test various manipulations in neurotrauma models aimed at eliciting a neurogenic response from them.In the present study,we systematically reviewed the experimental protocols and findings described in the scientific literature,which were peer-reviewed original research articles(1)describing preclinical experimental studies,(2)investigating NG2 cells,(3)associated with neurogenesis and neurotrauma,and(4)in vitro and/or in vivo,available in PubMed/MEDLINE,Web of Science or SCOPUS,from 1998 to 2022.Here,we have reviewed a total of 1504 papers,and summarized findings that ultimately suggest that NG2 cells possess an inducible neurogenic potential in animal models and in vitro.We also discriminate findings of NG2 neurogenesis promoted by different pharmacological and genetic approaches over functional and biochemical outcomes of traumatic brain injury and spinal co rd injury models,and provide mounting evidence for the potential benefits of manipulated NG2 cell ex vivo transplantation in primary injury treatment.These findings indicate the feasibility of NG2 cell neurogenesis strategies and add new players in the development of therapeutic alternatives for neurotrauma.
基金supported by grants from the National Natural Science Foundation of China(32100798)the China Postdoctoral Science Foundation(2021M700821).
文摘Cerebral small vessel disease(CSVD)is one of the most prevalent pathologic processes affecting 5%of people over 50 years of age and contributing to 45%of dementia cases.Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion,impaired cerebral vascular reactivity,and leakage of the blood–brain barrier in CSVD.However,the pathogenesis of CSVD remains elusive thus far,and no radical treatment has been developed.NG2 glia,also known as oligodendrocyte precursor cells,are the fourth type of glial cell in addition to astrocytes,microglia,and oligodendrocytes in the mammalian central nervous system.Many novel functions for NG2 glia in physiological and pathological states have recently been revealed.In this review,we discuss the role of NG2 glia in CSVD and the underlying mechanisms.
文摘Oligodendrocyte precursor cells(OPCs)and microglia are two very fascinating cell types with a multitude of important but different functions.At a first glance,they appear not to share many cellular properties,nor are directly related to one another or derived from a common ancestor.Despite all differences,emerging data show that both cell types express the protein nerve/glial antigen 2(NG2)after pathological insults(Figure 1).For years,it remained controversial whether microglia really could express NG2 upon injury,with contradictory results reported among different disease models.Addressing this question,we could recently show by using triple transgenic knock-in mice and either an acute injury model(stab wound injury)or the middle cerebral artery occlusion combined with immunohistochemistry that a subset of microglia activates the cspg4 gene in a disease dependent manner leading to a bonafide microglia-specific NG2 protein expression besides OPCs and pericytes.Our data show that the cspg4 gene not only gets transcribed in microglia based on reporter expression after recombination,but also the protein itself is expressed(Huang et al.,2020).
基金funded by the KRIBB Research Initiative Program,No.KGM0321112 to Y.HongBioGreen 21 Program,No.20110301-061-542-03-00 to Y.Hong,Rural Development Administration,Republic of Korea
文摘Previous studies have demonstrated that melatonin combined with exercise can alleviate secondary damage after spinal cord injury in rats. Therefore, it is hypothesized that melatonin combined with exercise can also alleviate ischemic brain damage. In this study, adult rats were subjected to right middle cerebral artery occlusion after receiving 10 mg/kg melatonin or vehicle subcutaneously twice daily for 14 days. Forced exercise using an animal treadmill was performed at 20 m/min for 30 minutes per day for 6 days prior to middle cerebral artery occlusion. After middle cerebral artery occlusion, each rat received melatonin combined with exercise, melatonin or exercise alone equally for 7 days until sacrifice. Interestingly, rats receiving melatonin combined with exercise exhibited more severe neurological deficits than those receiving melatonin or exercise alone. Hypoxia-inducible factor la mRNA in the brain tissue was upregulated in rats receiving melatonin combined with exercise. Similarly, microtubule associated protein-2 mRNA expression was significantly upregulated in rats receiving melatonin alone. Chondroitin sulfate proteoglycan 4 （NG2） mRNA expression was significantly decreased in rats receiving melatonin combined with exercise as well as in rats receiving exercise alone. Furthermore, neural cell loss in the primary motor cortex was significantly reduced in rats receiving melatonin or exercise alone, but the change was not observed in rats receiving melatonin combined with exercise. These findings suggest that excessive intervention with melatonin, exercise or their combination may lead to negative effects on ischemia/reperfusion-induced brain damage.
基金supported by grants from the US National Institutes of Healththe National Multiple Sclerosis Societythe Connecticut Stem Cell Research Program
文摘Polydendrocytes （NG2 cells） are a distinct type of glia that populate the developing and adult central nervous systems （CNS）. In the adult CNS, they retain mitotic activity and represent the largest proliferating cell popula- tion. Genetic and epigenetic mechanisms regulate the fate of polydendrocytes, which give rise to both oligo- dendrocytes and astrocytes. In addition, polydendrocytes actively differentiate into myelin-forming oligodendro- cytes in response to demyelination. This review summarizes the current knowledge regarding polydendrocyte development, which provides an important basis for understanding the mechanisms that lead to the remyelina- tion of demyelinated lesions.
基金supported by NIH grants(NS 030800 and NS 077942) to RHM
文摘Cellular therapies are becoming a major focus for the treatment of demyelinating diseases such as multiple sclerosis （MS）, therefore it is important to identify the most effective cell types that promote myelin repair. Several components contribute to the relative benefits of specific cell types including the overall efficacy of the cell therapy, the reproducibility of treatment, the mechanisms of action of distinct cell types and the ease of isolation and generation of therapeutic populations. A range of distinct cell populations promote functional recovery in animal models of MS including neural stem cells and mesenchymal stem cells derived from different tissues. Each of these cell populations has advantages and disadvantages and likely works through distinct mechanisms. The relevance of such mechanisms to myelin repair in the adult central nervous system is unclear since the therapeutic cells are generally derived from developing animals. Here we describe the isolation and characterization of a population of neural cells from the adult spinal cord that are characterized by the expression of the cell surface glycoprotein NG2. In functional studies, injection of adult NG2~ cells into mice with ongoing MOG3~_~5-induced experimental autoimmune encephalomyelitis （EAE） enhanced remyelination in the CNS while the number of CD3＋ T cells in areas of spinal cord demyelination was reduced approximately three-fold. In vivostudies indicated that in EAE, NG2＊ cells stimulated endogenous repair while in vitro they responded to signals in areas of induced inflammation by differentiating into oligodendrocytes. These results suggested that adult NG2~ cells represent a useful cell population for promoting neural repair in a variety of different conditions including demyelinating diseases such as MS.
基金supported by NIH NS079631,Shriners Hospitals for Children and Craig H.Neilsen Foundation
文摘Have you heard of NG2 cells or NG2 glia or polydendro- cytes~. These are new names for the precursor cells that used to be referred to as oligodendrocyte precursor cells （OPCs）, which become the oligodendrocytes that myelinate central nervous system （CNS） axons. Evidence suggests, however, that they have other functions, besides differentiating into oligodendrocytes. Most notably, the OPCs/NG2 cells are uni- formly distributed in grey matter as well as in white matter, which matches poorly with the distribution of myelinating oligodendrocytes. Furthermore, not every NG2 cell is fated to become an oligodendrocyte. Hence the term OPC can be fairly applied only when discussing the role of these cells in the oligodendrocyte lineage.
基金sponsored by the Natural Science Foundation of Guangdong Province,No. 8151018201000030Science and Technology Project of Guangzhou Municipal Universities,No. 08A072
文摘Rat models of T10 spinal cord injury were established with a clamp method. NG2 expression was detected with immunohistochemical staining and western blot. Ten days after spinal cord injury, the number of NG2-positive cells in the damaged areas and NG2 absorbance were both significantly increased. The findings indicate that acute T10 spinal cord injury in rats can lead to upregulation of NG2 protein expression in damaged areas.
