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
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
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
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
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
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
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
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
Neurovascular disorders, such as traumatic brain injury and stroke, persist as leading causes of death and disability - thus, the search for novel therapeutic approaches for these disorders continues. Many hurdles hav...Neurovascular disorders, such as traumatic brain injury and stroke, persist as leading causes of death and disability - thus, the search for novel therapeutic approaches for these disorders continues. Many hurdles have hindered the translation of effective therapies for traumatic brain injury and stroke primarily because of the inherent complexity of neuropathologies and an inability of current treatment approaches to adapt to the unique cell death pathways that accompany the disorder symptoms. Indeed, developing potent treatments for brain injury that incorporate dynamic and multiple disorder-engaging therapeutic targets are likely to produce more effective outcomes than traditional drugs. The therapeutic use of hypothermia presents a promising option which may fit these criteria. While regulated temperature reduction has displayed great promise in preclinical studies of brain injury, clinical trials have been far less consistent and associated with adverse effects, especially when hypothermia is pursued via systemic cooling. Accordingly, devising better methods of inducing hypothermia may facilitate the entry of this treatment modality into the clinic. The use of the delta opioid peptide D-alanine D-leucine enkephalin(DADLE) to pharmacologically induce temperature reduction may offer a potent alternative, as DADLE displays both the ability to cause temperature reduction and to confer a broad profile of other neuroprotective and neuroregenerative processes. This review explores the prospect of DADLE-mediated hypothermia to treat neurovascular brain injuries, emphasizing the translational steps necessary for its clinical translation.展开更多
Stroke persists as a global health and economic crisis,yet only two interventions to reduce stroke-induced brain injury exist.In the clinic,many patients who experience an ischemic stroke often further suffer from ret...Stroke persists as a global health and economic crisis,yet only two interventions to reduce stroke-induced brain injury exist.In the clinic,many patients who experience an ischemic stroke often further suffer from retinal ischemia,which can inhibit their ability to make a functional recovery and may diminish their overall quality of life.Despite this,no treatments for retinal ischemia have been developed.In both cases,ischemia-induced mitochondrial dysfunction initiates a cell loss cascade and inhibits endogenous brain repair.Stem cells have the ability to transfer healthy and functional mitochondria not only ischemic neurons,but also to similarly endangered retinal cells,replacing their defective mitochondria and thereby reducing cell death.In this review,we encapsulate and assess the relationship between cerebral and retinal ischemia,recent preclinical advancements made using in vitro and in vivo retinal ischemia models,the role of mitochondrial dysfunction in retinal ischemia pathology,and the therapeutic potential of stem cell-mediated mitochondrial transfer.Furthermore,we discuss the pitfalls in classic rodent functional assessments and the potential advantages of laser Doppler as a metric of stroke progression.The studies evaluated in this review highlight stem cell-derived mitochondrial transfer as a novel therapeutic approach to both retinal ischemia and stroke.Furthermore,we posit the immense correlation between cerebral and retinal ischemia as an underserved area of study,warranting exploration with the aim of these treating injuries together.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
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
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
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).
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.
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.
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 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.
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 NIH R01NS071956,NIH R01 NS090962,NIH R21NS089851,NIH R21 NS094087,DOD W81XWH-11-1-0634,and VA Merit Review I01 BX001407(to CVB)
文摘Neurovascular disorders, such as traumatic brain injury and stroke, persist as leading causes of death and disability - thus, the search for novel therapeutic approaches for these disorders continues. Many hurdles have hindered the translation of effective therapies for traumatic brain injury and stroke primarily because of the inherent complexity of neuropathologies and an inability of current treatment approaches to adapt to the unique cell death pathways that accompany the disorder symptoms. Indeed, developing potent treatments for brain injury that incorporate dynamic and multiple disorder-engaging therapeutic targets are likely to produce more effective outcomes than traditional drugs. The therapeutic use of hypothermia presents a promising option which may fit these criteria. While regulated temperature reduction has displayed great promise in preclinical studies of brain injury, clinical trials have been far less consistent and associated with adverse effects, especially when hypothermia is pursued via systemic cooling. Accordingly, devising better methods of inducing hypothermia may facilitate the entry of this treatment modality into the clinic. The use of the delta opioid peptide D-alanine D-leucine enkephalin(DADLE) to pharmacologically induce temperature reduction may offer a potent alternative, as DADLE displays both the ability to cause temperature reduction and to confer a broad profile of other neuroprotective and neuroregenerative processes. This review explores the prospect of DADLE-mediated hypothermia to treat neurovascular brain injuries, emphasizing the translational steps necessary for its clinical translation.
基金funded by the National Institutes of Health(NIH)R01NS071956,NIH R01NS090962,NIH R21NS089851,NIH R21NS094087Veterans Affairs Merit Review I01 BX001407(all to CVB)
文摘Stroke persists as a global health and economic crisis,yet only two interventions to reduce stroke-induced brain injury exist.In the clinic,many patients who experience an ischemic stroke often further suffer from retinal ischemia,which can inhibit their ability to make a functional recovery and may diminish their overall quality of life.Despite this,no treatments for retinal ischemia have been developed.In both cases,ischemia-induced mitochondrial dysfunction initiates a cell loss cascade and inhibits endogenous brain repair.Stem cells have the ability to transfer healthy and functional mitochondria not only ischemic neurons,but also to similarly endangered retinal cells,replacing their defective mitochondria and thereby reducing cell death.In this review,we encapsulate and assess the relationship between cerebral and retinal ischemia,recent preclinical advancements made using in vitro and in vivo retinal ischemia models,the role of mitochondrial dysfunction in retinal ischemia pathology,and the therapeutic potential of stem cell-mediated mitochondrial transfer.Furthermore,we discuss the pitfalls in classic rodent functional assessments and the potential advantages of laser Doppler as a metric of stroke progression.The studies evaluated in this review highlight stem cell-derived mitochondrial transfer as a novel therapeutic approach to both retinal ischemia and stroke.Furthermore,we posit the immense correlation between cerebral and retinal ischemia as an underserved area of study,warranting exploration with the aim of these treating injuries together.
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).
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,
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.