This perspective focuses on the recent literature regarding the role of the gut-brain axis(GBA) in fecal microbiota transplantation(FMT) and stem cell therapy(SCT) in Parkinson's disease(PD).PD is the second most ...This perspective focuses on the recent literature regarding the role of the gut-brain axis(GBA) in fecal microbiota transplantation(FMT) and stem cell therapy(SCT) in Parkinson's disease(PD).PD is the second most common neurodegenerative disease in the United States,yet therapies remain limited.Current research suggests that the GBA may play a role in the pathogenesis of PD.GBAbased FMT as well as SCT offer promising new avenues for PD treatment.Pro bing the interactions between FMT and SCT with the GBA may reveal novel therapeutics for PD.展开更多
Introduction:Traumatic brain injury(TBI)is a common diagnosis among veterans secondary to combat experiences.TBI is also rampant among those experiencing homelessness,possibly due to veterans making up 12.3%of the hom...Introduction:Traumatic brain injury(TBI)is a common diagnosis among veterans secondary to combat experiences.TBI is also rampant among those experiencing homelessness,possibly due to veterans making up 12.3%of the homeless population(Tsai and Rosenheck,2015),or due to the high risk of violence or trauma among those experiencing homelessness.TBI is up to 10×more prevalent among those experiencing homelessness(Stubbs et al.,2020;Dell et al.,2021).展开更多
Microvascular alterations within and outside the central nervous system(CNS)in amyotrophic lateral sclerosis(ALS):ALS is a fatal neurodegenerative disease leading to paralysis and eventual death within 3 to 5 years of...Microvascular alterations within and outside the central nervous system(CNS)in amyotrophic lateral sclerosis(ALS):ALS is a fatal neurodegenerative disease leading to paralysis and eventual death within 3 to 5 years of diagnosis due to respiratory dysfunction.Numerous pathogenic intrinsic and extrinsic effectors are involved in the diffuse motor neuron degeneration.Also,impairment of neurovascular unit components in the brain and spinal cord in ALS patients and in animal models of disease was noted and points to vascular pathology being a key factor in the recognition of ALS as a neurovascular disease(Garbuzova-Davis et al.,2011).展开更多
Dystonia characterizes a group of neurological movement disorders characterized by abnormal muscle movements,often with repetitive or sustained contraction resulting in abnormal posturing.Different types of dystonia p...Dystonia characterizes a group of neurological movement disorders characterized by abnormal muscle movements,often with repetitive or sustained contraction resulting in abnormal posturing.Different types of dystonia present based on the affected body regions and play a prominent role in determining the potential efficacy of a given intervention.For most patients afflicted with these disorders,an exact cause is rarely identified,so treatment mainly focuses on symptomatic alleviation.Pharmacological agents,such as oral anticholinergic administration and botulinum toxin injection,play a major role in the initial treatment of patients.In more severe and/or refractory cases,focal areas for neurosurgical intervention are identified and targeted to improve quality of life.Deep brain stimulation(DBS)targets these anatomical locations to minimize dystonia symptoms.Surgical ablation procedures and peripheral denervation surgeries also offer potential treatment to patients who do not respond to DBS.These management options grant providers and patients the ability to weigh the benefits and risks for each individual patient profile.This review article explores these pharmacological and neurosurgical management modalities for dystonia,providing a comprehensive assessment of each of their benefits and shortcomings.展开更多
Spinal cord injury is a very common pathological event that has devastating functional consequences in patients. In recent years, several research groups are trying to find an effective therapy that could be applied i...Spinal cord injury is a very common pathological event that has devastating functional consequences in patients. In recent years, several research groups are trying to find an effective therapy that could be applied in clinical practice. In this study, we analyzed the combination of different strategies as a potential therapy for spinal cord injury. Immunization with neural derived peptides(INDP), inhibition of glial scar formation(dipyridyl: DPY), as well as the use of biocompatible matrix(fibrin glue: FG) impregnated with bone marrow mesenchymal stem cells(MSCs) were combined and then its beneficial effects were evaluated in the induction of neuroprotection and neuroregeneration after acute SCI. Sprague-Dawley female rats were subjected to a moderate spinal cord injury and then randomly allocated into five groups: 1) phosphate buffered saline; 2) DPY; 3) INDP + DPY; 4) DPY+ FG; 5) INDP + DPY + FG + MSCs. In all rats, intervention was performed 72 hours after spinal cord injury. Locomotor and sensibility recovery was assessed in all rats. At 60 days after treatment, histological examinations of the spinal cord(hematoxylin-eosin and Bielschowsky staining) were performed. Our results showed that the combination therapy(DPY+ INDP + FG+ MSCs) was the best strategy to promote motor and sensibility recovery. In addition, significant increases in tissue preservation and axonal density were observed in the combination therapy group. Findings from this study suggest that the combination theapy(DPY+ INDP + FG + MSCs) exhibits potential effects on the protection and regeneration of neural tissue after acute spinal cord injury. All procedures were approved by the Animal Bioethics and Welfare Committee(approval No. 178544; CSNBTBIBAJ 090812960)on August 15, 2016.展开更多
The pathologic process of chronic phase traumatic brain injury is associated with spreading inflamma- tion, cell death, and neural dysfunction. It is thought that sequestration of inflammatory mediators can facilitate...The pathologic process of chronic phase traumatic brain injury is associated with spreading inflamma- tion, cell death, and neural dysfunction. It is thought that sequestration of inflammatory mediators can facilitate recovery and promote an environment that fosters cellular regeneration. Studies have targeted post-traumatic brain injury inflammation with the use of pharmacotherapy and cell therapy. These thera- peutic options are aimed at reducing the edematous and neurodegenerative inflammation that have been associated with compromising the integrity of the blood-brain barrier. Although studies have yielded posi- tive results from anti-inflammatory pharmacotherapy and cell therapy individually, emerging research has begun to target inflammation using combination therapy. The joint use of anti-inflammatory drugs along- side stem cell transplantation may provide better clinical outcomes for traumatic brain injury patients. Despite the promising results in this field of research, it is important to note that most of the studies men- tioned in this review have completed their studies using animal models. Translation of this research into a clinical setting will require additional laboratory experiments and larger predinical trials.展开更多
TBI pathology： Traumatic brain injury （TBI） is caused by an external force to the head, resulting in trauma to the brain. Approximately 1.7 million Americans suffer from TBI every year. Out of the 1.7 million suffe...TBI pathology： Traumatic brain injury （TBI） is caused by an external force to the head, resulting in trauma to the brain. Approximately 1.7 million Americans suffer from TBI every year. Out of the 1.7 million suffering from TBI, an estimated 52,000 injuries result in death, leaving a mass amount of peo- ple with symptoms that could last a few days, a few years, or their entire life （Faul et al., 2010）. TBI can be classified as mild, moderate and severe. Depending on the classification and the extent of the injury, TBI can cause both physical symptoms and cognitive disorders （Lozano et al., 2015）.展开更多
Transplantation of human bone marrow mesenchymal stem cells(hMSCs) stands as a potent stroke therapy, but its exact mechanism remains unknown. This study investigated the anti-apoptotic mechanisms by which hMSCs exert...Transplantation of human bone marrow mesenchymal stem cells(hMSCs) stands as a potent stroke therapy, but its exact mechanism remains unknown. This study investigated the anti-apoptotic mechanisms by which hMSCs exert neuroprotective effects on cerebral ischemia. Primary mixed cultures of rat neurons and astrocytes were cultured and exposed to oxygen-glucose deprivation. A two-hour period of "reperfusion" in standard medium and normoxic conditions was allowed and immediately followed by hMSCs and/or Bcl-2 antibody treatment. Cell viability of primary rat neurons and astrocytes was determined by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide and trypan blue exclusion methods. hMSC survival and differentiation were characterized by immunocytochemistry, while the concentration of Bcl-2 in the supernatant was measured by enzyme-linked immunosorbent assay to reveal the secretory anti-apoptotic function of hMSCs. Cultured hMSCs expressed embryonic-like stem cell phenotypic markers CXCR4, Oct4, SSEA4, and Nanog, as well as immature neural phenotypic marker Nestin. Primary rat neurons and astrocytes were protected from oxygen-glucose deprivation by hMSCs, which was antagonized by the Bcl-2 antibody. However, Bcl-2 levels in the supernatants did not differ between hMSCand non-treated cells exposed to oxygen-glucose deprivation. Neuroprotective effects of hMSCs against cerebral ischemia were partially mediated by the anti-apoptotic mechanisms. However, further studies are warranted to fully elucidate this pathway.展开更多
Oxidative stress is closely associated with secondary cell death in many disorders of the central nervous system including stroke, Parkinson＇s disease, Alzheimer＇s disease. Among many aber-rant oxidative stress-asso...Oxidative stress is closely associated with secondary cell death in many disorders of the central nervous system including stroke, Parkinson＇s disease, Alzheimer＇s disease. Among many aber-rant oxidative stress-associated proteins, DJ-1 has been associated with the oxidative stress cell death cascade primarily in Parkinson＇s disease. Although principally expressed in the cytoplasm and nucleus, DJ-1 can be secreted into the serum under pathological condition. Recently, a close pathological association between DJ-I and oxidative stress in stroke has been implicated. To this end, we and others have demonstrated the important role of mitochondria in neuroprotection for stroke by demonstrating that the translocation of DJ-1 in the mitochondria could potentially mitigate mitochondrial injury. Here, we discuss our recent findings testing the hypothesis that DJ- 1 not only functions as a form of intracellular protection from oxidative stress, but that it also utilizes paracrine and/or autocrine cues in order to accomplish extracellular signaling between neighboring neuronal cells, resulting in neuroprotection. This article highlights recent evidence supporting the status of DJ-1 as key anti-oxidative stress therapeutic target for stroke.展开更多
Acupuncture at the SJ5（Waiguan） acupoint has neuroprotective effects in cerebral infarction, but the underlying mechanism remains poorly understood. Here, we analyzed gene expression in healthy rat cerebellum using ...Acupuncture at the SJ5（Waiguan） acupoint has neuroprotective effects in cerebral infarction, but the underlying mechanism remains poorly understood. Here, we analyzed gene expression in healthy rat cerebellum using a pathway-focused DNA microarray to screen 113 genes associated with 18 signal transduction pathways. After 20 minutes of acupuncture at SJ5, the expression of Bcl-2 and Birc1 b m RNA was markedly increased. This was confirmed by real-time reverse transcription PCR. Furthermore, western blot analysis showed that Bcl-2 protein expression remained high in the cerebellum until at least 2 hours after cessation of acupuncture. These findings indicate that acupuncture at SJ5 exerts neuroprotective effects by regulating the expression of anti-apoptotic gene Bcl-2.展开更多
Deleterious inflammatory cell invasion has been implicated in neurological diseases,partly manifesting as a leaky blood-central nervous system ba rrier(BCNSB)(Huang et al.,2021).Uncovering the perturbations of the neu...Deleterious inflammatory cell invasion has been implicated in neurological diseases,partly manifesting as a leaky blood-central nervous system ba rrier(BCNSB)(Huang et al.,2021).Uncovering the perturbations of the neurovascular unit(NVU)may reveal the role of detrimental proinflammatory cells and signaling molecules in disrupting the central nervous system immuneprivileged environment.展开更多
Essentially, the knowledge of science alone offers little utility. With-out the ability to investigate, apply and communicate, science serves no purpose. That is not to undermine the importance of scientific knowledge...Essentially, the knowledge of science alone offers little utility. With-out the ability to investigate, apply and communicate, science serves no purpose. That is not to undermine the importance of scientific knowledge, but there currently exists a major flaw in our high school educational system that inhibits meaningful learning experiences for most students. Application of science in local high schools is largely directed at improving performance on multiple-choice exams. Standardized tests taken by high school students are slowly progressing,展开更多
There is currently no consensus among clinicians and scientists over the appropriate or optimal timing for umbilical cord clamping. However, many clinical studies have suggested that delayed cord clamping is associate...There is currently no consensus among clinicians and scientists over the appropriate or optimal timing for umbilical cord clamping. However, many clinical studies have suggested that delayed cord clamping is associated with various neonatal benefits including increased blood volume, reduced need for blood transfusion, increased cerebral oxygenation in pre-term infants, and decreased frequency of iron deficiency anemia in term infants. Human umbilical cord blood con- tains significant amounts of stem and progenitor cells and is currently used in the treatment of several life-threatening diseases. We propose that delayed cord clamping be encouraged as it en- hances blood flow from the placenta to the neonate, which is accompanied by an increase supply of valuable stem and progenitor cells, as well as may improve blood oxygenation and increase blood volume, altogether reducing the infant＇s susceptibility to both neonatal and age-related diseases.展开更多
Stem cells may be the future of therapeutics for stroke due to their regenerative and immunomodulatory capabilities.Major barriers faced when employing stem cells,however,include faulty migration,low cell survival,and...Stem cells may be the future of therapeutics for stroke due to their regenerative and immunomodulatory capabilities.Major barriers faced when employing stem cells,however,include faulty migration,low cell survival,and diminished proliferation.M ultilineage-differentiating stress ensuring (Muse) cells,a subset of mesenchymal stem cells,overcome these barriers.Muse cells aid in neuroregeneration,have immense regenerative potential,and are pluripotent,non-tumorigenic,and immunomodulatory.In stroke specifically,these cells may restore an a nti-inflammatory environment,regenerate damaged neurons,and integrate into the neuronal architecture.In fact,Muse cells may be aptly designed to ameliorate neurovascular unit damage following stroke and observed in other neuroinflammatory disorders.展开更多
Bioethics falls within the controversial ethical issues from the new advances and emerging technology in pre-clinical and clinical settings which inspired medical policy and practice.The purpose of this paper is to pr...Bioethics falls within the controversial ethical issues from the new advances and emerging technology in pre-clinical and clinical settings which inspired medical policy and practice.The purpose of this paper is to present an overview of ethical issues in stem cell-based therapies and to provide substantial argument for the need ofa Bioethics Research Consortium that will be tasked with convening a disciplined board of experts that will apply their principles to biomedical research,and emerging technology to further stipulate the socioeconomic influence of such entities and their therapeutic impact to society.Not too long ago,the successful therapeutic studies in Parkinson's disease and stroke were the highlights of bioethical issues.The precedent for study selection was based on public feedback,government reception,and scientific analyses developed by these spearhead studies.From all the negative publicity that researchers have been getting before,the whiplash from decades of fear and misunderstanding has hindered the progress of scientific study.There is a huge figurative tug of war between what is making profit and what is needed to improve the health of afflicted patients worldwide.Poor management of education and funding may have actually hindered potential life changing cures and treatments from coming to fruition.We propose the creation of a Bioethics Research Consortium that would determine how ethical matters are handled with careful consideration to public need.The goal is to restructure drug development policy,and improve upon the ways in which research methods and funds are handled today.展开更多
Amyotrophic lateral sclerosis(ALS)is a rapidly fatal neurological disease characterized by upper and lower motor neuron degeneration.Though typically idiopathic,familial forms of ALS are commonly composed of a superox...Amyotrophic lateral sclerosis(ALS)is a rapidly fatal neurological disease characterized by upper and lower motor neuron degeneration.Though typically idiopathic,familial forms of ALS are commonly composed of a superoxide dismutase 1(SOD1)mutation.Basic science frequently utilizes SOD1 models in vitro and in vivo to replicate ALS conditions.Therapies are sparse;those that exist in the market extend life minimally,thus driving the demand for research to identify novel therapeutics.Transplantation of stem cells is a promising approach for many diseases and has shown efficacy in SOD1 models and clinical trials.The underlying mechanism for stem cell therapy presents an exciting venue for research investigations.Most notably,the paracrine actions of stem cell-derived extracellular vesicles(EVs)have been suggested as a potent mitigating factor.This literature review focuses on the most recent preclinical research investigating cellfree methods for treating ALS.Various avenues are being explored,differing on the EV contents(protein,microRNA,etc.)and on the cell target(astrocyte,endothelial cell,motor neuron-like cells,etc.),and both molecular and behavioral outcomes are being examined.Unfortunately,EVs may also play a role in propagating ALS pathology.Nonetheless,the overarching goal remains clear:to identify efficient cell-free techniques to attenuate the deadly consequences of ALS.展开更多
Injury to the central nervous system (CNS) is common, and though it has been well studied, many aspects of traumatic brain injury (TBI) and stroke are poorly understood. TBI and stroke are two pathologic events that c...Injury to the central nervous system (CNS) is common, and though it has been well studied, many aspects of traumatic brain injury (TBI) and stroke are poorly understood. TBI and stroke are two pathologic events that can cause severe, immediate impact to the neurostructure and function of the CNS, which has been recognized recently to be exacerbated by the body's own immune response. Although the brain damage induced by the initial trauma is most likely unsalvageable, the secondary immunologic deterioration of neural tissue gives ample opportunity for therapeutic strategists seeking to mitigate TBI's secondary detrimental effects. The purpose of this paper is to highlight the cell death mechanisms associated with CNS injury with special emphasis on inflammation. The authors discuss sources of inflammation, and introduce the role of the spleen in the systemic response to inflammation after CNS injury.展开更多
There may be a pathological connection between cardiac failure and ischemic stroke.In this article we describe pertinent research that demonstrates subsequent death of cardiac and neural myocytes in the post ischemic ...There may be a pathological connection between cardiac failure and ischemic stroke.In this article we describe pertinent research that demonstrates subsequent death of cardiac and neural myocytes in the post ischemic stroke brain.Current stroke therapy overlooks the connection between cardiac and cerebrovascular events and fails to address the shared risk factors.Current pre-clinical stroke investigations have provided evidence that suggests the presence of an indirect cell death pathway in which toxic molecules emanate from the stroke brain and trigger cardiac cell death.On the other hand,other studies highlight the presence of a reverse cell death cascade in which toxic molecules from the heart,following cardiac arrest,travel to the brain and induce ischemic cell death.Further examination of these putative cell death pathways between ischemic stroke and cardiac arrest will prompt the advancement of innovative treatments specifically targeting both diseases,leading to ameliorated clinical results of patients diagnosed with heart failure and ischemic stroke.展开更多
The mechanism underlying the pathogenesis of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection in humans is poorly understood,although the cellular receptors which facilitate the virus fusion have b...The mechanism underlying the pathogenesis of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection in humans is poorly understood,although the cellular receptors which facilitate the virus fusion have been identified.Although the major symptoms of the infection have been identified as acute respiratory distress,pneumonia,and fever,recently,symptoms involving nervous system dysfunctions,including encephalopathy and stroke,have been detected.Herein,we comprehensively review the evidence that SARS-CoV-2 infection involves a neurotropic mechanism including a nose-brain-lung axis suggesting implications in therapy development.展开更多
Here,we compiled ten papers detailing recent strides in the field of stem cell therapy,which address critical issues relevant to pursuing this experimental treatment for clinical applications in brain disorders.Topics...Here,we compiled ten papers detailing recent strides in the field of stem cell therapy,which address critical issues relevant to pursuing this experimental treatment for clinical applications in brain disorders.Topics include efficacy,safety,and mechanism of action underlying cell therapy,emerging technologies and combination pharmacotherapies with cell transplantation directed at improving the functional outcomes,and evaluation of key translational components of advancing novel therapeutics to the clinic,including the need for vis-a-vis comparisons with the gold standard of treatment post-injury (i.e.,physical rehabilitation).A bioethics paper is also incorporated here to further appreciate the current status of cell therapy in the community setting.The overall goal of this special volume is to provoke a meaningful assessment of the lessons we have learned in recent years and to use such knowledge to carefully translate safe and effective applications of cell therapy,and its mechanism of action for the treatment of neurological disorders.展开更多
文摘This perspective focuses on the recent literature regarding the role of the gut-brain axis(GBA) in fecal microbiota transplantation(FMT) and stem cell therapy(SCT) in Parkinson's disease(PD).PD is the second most common neurodegenerative disease in the United States,yet therapies remain limited.Current research suggests that the GBA may play a role in the pathogenesis of PD.GBAbased FMT as well as SCT offer promising new avenues for PD treatment.Pro bing the interactions between FMT and SCT with the GBA may reveal novel therapeutics for PD.
文摘Introduction:Traumatic brain injury(TBI)is a common diagnosis among veterans secondary to combat experiences.TBI is also rampant among those experiencing homelessness,possibly due to veterans making up 12.3%of the homeless population(Tsai and Rosenheck,2015),or due to the high risk of violence or trauma among those experiencing homelessness.TBI is up to 10×more prevalent among those experiencing homelessness(Stubbs et al.,2020;Dell et al.,2021).
基金This work was supported by the National Instites of Health,National Institute of Neurological Disorders and Stroke(1R01NS090962).
文摘Microvascular alterations within and outside the central nervous system(CNS)in amyotrophic lateral sclerosis(ALS):ALS is a fatal neurodegenerative disease leading to paralysis and eventual death within 3 to 5 years of diagnosis due to respiratory dysfunction.Numerous pathogenic intrinsic and extrinsic effectors are involved in the diffuse motor neuron degeneration.Also,impairment of neurovascular unit components in the brain and spinal cord in ALS patients and in animal models of disease was noted and points to vascular pathology being a key factor in the recognition of ALS as a neurovascular disease(Garbuzova-Davis et al.,2011).
文摘Dystonia characterizes a group of neurological movement disorders characterized by abnormal muscle movements,often with repetitive or sustained contraction resulting in abnormal posturing.Different types of dystonia present based on the affected body regions and play a prominent role in determining the potential efficacy of a given intervention.For most patients afflicted with these disorders,an exact cause is rarely identified,so treatment mainly focuses on symptomatic alleviation.Pharmacological agents,such as oral anticholinergic administration and botulinum toxin injection,play a major role in the initial treatment of patients.In more severe and/or refractory cases,focal areas for neurosurgical intervention are identified and targeted to improve quality of life.Deep brain stimulation(DBS)targets these anatomical locations to minimize dystonia symptoms.Surgical ablation procedures and peripheral denervation surgeries also offer potential treatment to patients who do not respond to DBS.These management options grant providers and patients the ability to weigh the benefits and risks for each individual patient profile.This review article explores these pharmacological and neurosurgical management modalities for dystonia,providing a comprehensive assessment of each of their benefits and shortcomings.
基金supported by the National Council of Science and Technology of Mexico(CONACYT),No.178544(to AI)
文摘Spinal cord injury is a very common pathological event that has devastating functional consequences in patients. In recent years, several research groups are trying to find an effective therapy that could be applied in clinical practice. In this study, we analyzed the combination of different strategies as a potential therapy for spinal cord injury. Immunization with neural derived peptides(INDP), inhibition of glial scar formation(dipyridyl: DPY), as well as the use of biocompatible matrix(fibrin glue: FG) impregnated with bone marrow mesenchymal stem cells(MSCs) were combined and then its beneficial effects were evaluated in the induction of neuroprotection and neuroregeneration after acute SCI. Sprague-Dawley female rats were subjected to a moderate spinal cord injury and then randomly allocated into five groups: 1) phosphate buffered saline; 2) DPY; 3) INDP + DPY; 4) DPY+ FG; 5) INDP + DPY + FG + MSCs. In all rats, intervention was performed 72 hours after spinal cord injury. Locomotor and sensibility recovery was assessed in all rats. At 60 days after treatment, histological examinations of the spinal cord(hematoxylin-eosin and Bielschowsky staining) were performed. Our results showed that the combination therapy(DPY+ INDP + FG+ MSCs) was the best strategy to promote motor and sensibility recovery. In addition, significant increases in tissue preservation and axonal density were observed in the combination therapy group. Findings from this study suggest that the combination theapy(DPY+ INDP + FG + MSCs) exhibits potential effects on the protection and regeneration of neural tissue after acute spinal cord injury. All procedures were approved by the Animal Bioethics and Welfare Committee(approval No. 178544; CSNBTBIBAJ 090812960)on August 15, 2016.
基金funded by NIH R01NS071956,NIH R01 NS090962,NIH R21NS089851,NIH R21 NS094087DOD W81XWH-11-1-0634VA Merit Review I01 BX001407 to CVB
文摘The pathologic process of chronic phase traumatic brain injury is associated with spreading inflamma- tion, cell death, and neural dysfunction. It is thought that sequestration of inflammatory mediators can facilitate recovery and promote an environment that fosters cellular regeneration. Studies have targeted post-traumatic brain injury inflammation with the use of pharmacotherapy and cell therapy. These thera- peutic options are aimed at reducing the edematous and neurodegenerative inflammation that have been associated with compromising the integrity of the blood-brain barrier. Although studies have yielded posi- tive results from anti-inflammatory pharmacotherapy and cell therapy individually, emerging research has begun to target inflammation using combination therapy. The joint use of anti-inflammatory drugs along- side stem cell transplantation may provide better clinical outcomes for traumatic brain injury patients. Despite the promising results in this field of research, it is important to note that most of the studies men- tioned in this review have completed their studies using animal models. Translation of this research into a clinical setting will require additional laboratory experiments and larger predinical trials.
文摘TBI pathology： Traumatic brain injury （TBI） is caused by an external force to the head, resulting in trauma to the brain. Approximately 1.7 million Americans suffer from TBI every year. Out of the 1.7 million suffering from TBI, an estimated 52,000 injuries result in death, leaving a mass amount of peo- ple with symptoms that could last a few days, a few years, or their entire life （Faul et al., 2010）. TBI can be classified as mild, moderate and severe. Depending on the classification and the extent of the injury, TBI can cause both physical symptoms and cognitive disorders （Lozano et al., 2015）.
基金Cesar V.Borlongan was funded by NIH R01NS071956,NIH R01 NS090962,NIH R21NS089851,NIH R21 NS094087VA Merit Review I01 BX001407
文摘Transplantation of human bone marrow mesenchymal stem cells(hMSCs) stands as a potent stroke therapy, but its exact mechanism remains unknown. This study investigated the anti-apoptotic mechanisms by which hMSCs exert neuroprotective effects on cerebral ischemia. Primary mixed cultures of rat neurons and astrocytes were cultured and exposed to oxygen-glucose deprivation. A two-hour period of "reperfusion" in standard medium and normoxic conditions was allowed and immediately followed by hMSCs and/or Bcl-2 antibody treatment. Cell viability of primary rat neurons and astrocytes was determined by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide and trypan blue exclusion methods. hMSC survival and differentiation were characterized by immunocytochemistry, while the concentration of Bcl-2 in the supernatant was measured by enzyme-linked immunosorbent assay to reveal the secretory anti-apoptotic function of hMSCs. Cultured hMSCs expressed embryonic-like stem cell phenotypic markers CXCR4, Oct4, SSEA4, and Nanog, as well as immature neural phenotypic marker Nestin. Primary rat neurons and astrocytes were protected from oxygen-glucose deprivation by hMSCs, which was antagonized by the Bcl-2 antibody. However, Bcl-2 levels in the supernatants did not differ between hMSCand non-treated cells exposed to oxygen-glucose deprivation. Neuroprotective effects of hMSCs against cerebral ischemia were partially mediated by the anti-apoptotic mechanisms. However, further studies are warranted to fully elucidate this pathway.
基金funded by USF School of Physical Therapy and Rehabilitation SciencesCVB,NT,and YK+2 种基金funded by USF Department of Neurosurgery and Brain Repair,NIH 1R01NS07195601A1Department of Defense W81XWH-11-1-0634the James and Esther King Biomedical Research Foundation 1KG01-33966
文摘Oxidative stress is closely associated with secondary cell death in many disorders of the central nervous system including stroke, Parkinson＇s disease, Alzheimer＇s disease. Among many aber-rant oxidative stress-associated proteins, DJ-1 has been associated with the oxidative stress cell death cascade primarily in Parkinson＇s disease. Although principally expressed in the cytoplasm and nucleus, DJ-1 can be secreted into the serum under pathological condition. Recently, a close pathological association between DJ-I and oxidative stress in stroke has been implicated. To this end, we and others have demonstrated the important role of mitochondria in neuroprotection for stroke by demonstrating that the translocation of DJ-1 in the mitochondria could potentially mitigate mitochondrial injury. Here, we discuss our recent findings testing the hypothesis that DJ- 1 not only functions as a form of intracellular protection from oxidative stress, but that it also utilizes paracrine and/or autocrine cues in order to accomplish extracellular signaling between neighboring neuronal cells, resulting in neuroprotection. This article highlights recent evidence supporting the status of DJ-1 as key anti-oxidative stress therapeutic target for stroke.
基金supported by the National Natural Science Foundation of China,No.81273672,81373720the Natural Science Foundation of Fujian Province of China,No.2014J01353a grant from Fujian Province Health Planning Commission Project(2014)for Training Young Talents,No.2014-ZQN-JC-28
文摘Acupuncture at the SJ5（Waiguan） acupoint has neuroprotective effects in cerebral infarction, but the underlying mechanism remains poorly understood. Here, we analyzed gene expression in healthy rat cerebellum using a pathway-focused DNA microarray to screen 113 genes associated with 18 signal transduction pathways. After 20 minutes of acupuncture at SJ5, the expression of Bcl-2 and Birc1 b m RNA was markedly increased. This was confirmed by real-time reverse transcription PCR. Furthermore, western blot analysis showed that Bcl-2 protein expression remained high in the cerebellum until at least 2 hours after cessation of acupuncture. These findings indicate that acupuncture at SJ5 exerts neuroprotective effects by regulating the expression of anti-apoptotic gene Bcl-2.
文摘Deleterious inflammatory cell invasion has been implicated in neurological diseases,partly manifesting as a leaky blood-central nervous system ba rrier(BCNSB)(Huang et al.,2021).Uncovering the perturbations of the neurovascular unit(NVU)may reveal the role of detrimental proinflammatory cells and signaling molecules in disrupting the central nervous system immuneprivileged environment.
文摘Essentially, the knowledge of science alone offers little utility. With-out the ability to investigate, apply and communicate, science serves no purpose. That is not to undermine the importance of scientific knowledge, but there currently exists a major flaw in our high school educational system that inhibits meaningful learning experiences for most students. Application of science in local high schools is largely directed at improving performance on multiple-choice exams. Standardized tests taken by high school students are slowly progressing,
基金funded by NIH NINDS RO1 1R01NS071956-01,NIH NINDS 1R21NS089851-01Department of Defense TATRC W811XWH-11-1-0634+1 种基金Veterans Affairs BX001407-01A2James and Esther King Biomedical Research Program 09KB-01-23123,and 1KG01-33966
文摘There is currently no consensus among clinicians and scientists over the appropriate or optimal timing for umbilical cord clamping. However, many clinical studies have suggested that delayed cord clamping is associated with various neonatal benefits including increased blood volume, reduced need for blood transfusion, increased cerebral oxygenation in pre-term infants, and decreased frequency of iron deficiency anemia in term infants. Human umbilical cord blood con- tains significant amounts of stem and progenitor cells and is currently used in the treatment of several life-threatening diseases. We propose that delayed cord clamping be encouraged as it en- hances blood flow from the placenta to the neonate, which is accompanied by an increase supply of valuable stem and progenitor cells, as well as may improve blood oxygenation and increase blood volume, altogether reducing the infant＇s susceptibility to both neonatal and age-related diseases.
基金CVB was funded by the National Institutes of Health NIH R01NS090962,NIH R01NS102395,NIH R21 NS1095 75CVB was funded and received royalties and stock options from Astellas,Asterias,Sanbio,Athersys,KMPHCInternational Stem Cell Corporation and has also received consultant compensation from Chiesi Farmaceutici。
文摘Stem cells may be the future of therapeutics for stroke due to their regenerative and immunomodulatory capabilities.Major barriers faced when employing stem cells,however,include faulty migration,low cell survival,and diminished proliferation.M ultilineage-differentiating stress ensuring (Muse) cells,a subset of mesenchymal stem cells,overcome these barriers.Muse cells aid in neuroregeneration,have immense regenerative potential,and are pluripotent,non-tumorigenic,and immunomodulatory.In stroke specifically,these cells may restore an a nti-inflammatory environment,regenerate damaged neurons,and integrate into the neuronal architecture.In fact,Muse cells may be aptly designed to ameliorate neurovascular unit damage following stroke and observed in other neuroinflammatory disorders.
文摘Bioethics falls within the controversial ethical issues from the new advances and emerging technology in pre-clinical and clinical settings which inspired medical policy and practice.The purpose of this paper is to present an overview of ethical issues in stem cell-based therapies and to provide substantial argument for the need ofa Bioethics Research Consortium that will be tasked with convening a disciplined board of experts that will apply their principles to biomedical research,and emerging technology to further stipulate the socioeconomic influence of such entities and their therapeutic impact to society.Not too long ago,the successful therapeutic studies in Parkinson's disease and stroke were the highlights of bioethical issues.The precedent for study selection was based on public feedback,government reception,and scientific analyses developed by these spearhead studies.From all the negative publicity that researchers have been getting before,the whiplash from decades of fear and misunderstanding has hindered the progress of scientific study.There is a huge figurative tug of war between what is making profit and what is needed to improve the health of afflicted patients worldwide.Poor management of education and funding may have actually hindered potential life changing cures and treatments from coming to fruition.We propose the creation of a Bioethics Research Consortium that would determine how ethical matters are handled with careful consideration to public need.The goal is to restructure drug development policy,and improve upon the ways in which research methods and funds are handled today.
文摘Amyotrophic lateral sclerosis(ALS)is a rapidly fatal neurological disease characterized by upper and lower motor neuron degeneration.Though typically idiopathic,familial forms of ALS are commonly composed of a superoxide dismutase 1(SOD1)mutation.Basic science frequently utilizes SOD1 models in vitro and in vivo to replicate ALS conditions.Therapies are sparse;those that exist in the market extend life minimally,thus driving the demand for research to identify novel therapeutics.Transplantation of stem cells is a promising approach for many diseases and has shown efficacy in SOD1 models and clinical trials.The underlying mechanism for stem cell therapy presents an exciting venue for research investigations.Most notably,the paracrine actions of stem cell-derived extracellular vesicles(EVs)have been suggested as a potent mitigating factor.This literature review focuses on the most recent preclinical research investigating cellfree methods for treating ALS.Various avenues are being explored,differing on the EV contents(protein,microRNA,etc.)and on the cell target(astrocyte,endothelial cell,motor neuron-like cells,etc.),and both molecular and behavioral outcomes are being examined.Unfortunately,EVs may also play a role in propagating ALS pathology.Nonetheless,the overarching goal remains clear:to identify efficient cell-free techniques to attenuate the deadly consequences of ALS.
文摘Injury to the central nervous system (CNS) is common, and though it has been well studied, many aspects of traumatic brain injury (TBI) and stroke are poorly understood. TBI and stroke are two pathologic events that can cause severe, immediate impact to the neurostructure and function of the CNS, which has been recognized recently to be exacerbated by the body's own immune response. Although the brain damage induced by the initial trauma is most likely unsalvageable, the secondary immunologic deterioration of neural tissue gives ample opportunity for therapeutic strategists seeking to mitigate TBI's secondary detrimental effects. The purpose of this paper is to highlight the cell death mechanisms associated with CNS injury with special emphasis on inflammation. The authors discuss sources of inflammation, and introduce the role of the spleen in the systemic response to inflammation after CNS injury.
文摘There may be a pathological connection between cardiac failure and ischemic stroke.In this article we describe pertinent research that demonstrates subsequent death of cardiac and neural myocytes in the post ischemic stroke brain.Current stroke therapy overlooks the connection between cardiac and cerebrovascular events and fails to address the shared risk factors.Current pre-clinical stroke investigations have provided evidence that suggests the presence of an indirect cell death pathway in which toxic molecules emanate from the stroke brain and trigger cardiac cell death.On the other hand,other studies highlight the presence of a reverse cell death cascade in which toxic molecules from the heart,following cardiac arrest,travel to the brain and induce ischemic cell death.Further examination of these putative cell death pathways between ischemic stroke and cardiac arrest will prompt the advancement of innovative treatments specifically targeting both diseases,leading to ameliorated clinical results of patients diagnosed with heart failure and ischemic stroke.
基金(This work is partly supported by a University of South Florida Pandemic Response Research Network funding for COVID-19 and Veterans Affairs Merit Review grant)(and Research Career Scientist Awards to Dr.Subhra Mohapatra)+4 种基金in partby the Department of Veterans AffairsVeterans Health AdministrationOffice of Research and Developmentthe contents of this report do not represent the views of the Department of Veterans Affairs or the United States Government
文摘The mechanism underlying the pathogenesis of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection in humans is poorly understood,although the cellular receptors which facilitate the virus fusion have been identified.Although the major symptoms of the infection have been identified as acute respiratory distress,pneumonia,and fever,recently,symptoms involving nervous system dysfunctions,including encephalopathy and stroke,have been detected.Herein,we comprehensively review the evidence that SARS-CoV-2 infection involves a neurotropic mechanism including a nose-brain-lung axis suggesting implications in therapy development.
文摘Here,we compiled ten papers detailing recent strides in the field of stem cell therapy,which address critical issues relevant to pursuing this experimental treatment for clinical applications in brain disorders.Topics include efficacy,safety,and mechanism of action underlying cell therapy,emerging technologies and combination pharmacotherapies with cell transplantation directed at improving the functional outcomes,and evaluation of key translational components of advancing novel therapeutics to the clinic,including the need for vis-a-vis comparisons with the gold standard of treatment post-injury (i.e.,physical rehabilitation).A bioethics paper is also incorporated here to further appreciate the current status of cell therapy in the community setting.The overall goal of this special volume is to provoke a meaningful assessment of the lessons we have learned in recent years and to use such knowledge to carefully translate safe and effective applications of cell therapy,and its mechanism of action for the treatment of neurological disorders.
