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| 1 | Neuroprotective effects of human bone marrow mesenchymal stem cells against cerebral ischemia are mediated in part by an anti-apoptotic mechanism显示文摘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. | Yuyang Zhang Seongjin Yu Julian P.Tuazon Jea-Young Lee Sydney Corey Lauren Kvederis Chase Kingsbury Yuji Kaneko Cesar V.Borlongan | 2019 | Neural Regeneration Research2019，14，4： | 9 |
| 2 | Enhancing endogenous stem cells in the newborn via delayed umbilical cord clamping显示文摘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 contains 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 enhances 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. | Christopher Lawton Sandra Acosta Nate Watson Chiara Gonzales-Portillo Theo Diamandis Naoki Tajiri Yuji Kaneko Paul R.Sanberg Cesar V.Borlongan | 2015 | Neural Regeneration Research2015，10，9： | 6 |
| 3 | Utilizing pharmacotherapy and mesenchymal stem cell therapy to reduce inflammation following traumatic brain injury显示文摘The pathologic process of chronic phase traumatic brain injury is associated with spreading inflammation,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 therapeutic 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 positive 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 alongside 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 mentioned 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 preclinical trials. | Sherwin Mashkouri Marci G.Crowley Michael G.Liska Sydney Corey Cesar V.Borlongan | 2016 | Neural Regeneration Research2016，11，9： | 5 |
| 4 | The role of DJ-1 in the oxidative stress cell death cascade after stroke显示文摘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 aberrant 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-1 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. | Paolina Pantcheva Maya Elias Kelsey Duncan Cesar V.Borlongan Naoki Tajiri Yuji Kaneko | 2014 | Neural Regeneration Research2014，9，15： | 5 |
| 5 | Neuroprotective and neuroregenerative potential of pharmacologically-induced hypothermia with D-alanine D-leucine enkephalin in brain injury显示文摘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. | M.Grant Liska Marci G.Crowley Julian P.Tuazon Cesar V.Borlongan | 2018 | Neural Regeneration Research2018，13，12： | 4 |
| 6 | Drug-and cell-based therapies for targeting neuroinflammation in traumatic brain injury显示文摘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 estimated52,000 injuries result in death,leaving a mass amount of people 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 | Sussannah Kaelber Paolina Pantcheva Cesar V.Borlongan | 2016 | Neural Regeneration Research2016，11，10： | 3 |
| 7 | Stroke gets in your eyes: stroke-induced retinal ischemia and the potential of stem cell therapy显示文摘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. | Chase Kingsbury Matt Heyck Brooke Bonsack Jea-Young Lee Cesar V.Borlongan | 2020 | Neural Regeneration Research2020，15，6： | 2 |
| 8 | Mannitol facilitates neurotrophic factor up‐regulation and behavioural recovery in neonatal hypoxic‐ischaemic rats with human umbilical cord blood grafts显示文摘 | T.Yasuhara K.Hara M.Maki L.Xu G.Yu M. M.Ali T.Masuda S. J.Yu E. K.Bae T.Hayashi N.Matsukawa Y.Kaneko N.Kuzmin‐Nichols S.Ellovitch E. L.Cruz S. K.Klasko C. D.Sanberg P. R.Sanberg C. V.Borlongan | 2010 | Journal of Cellular and Molecular Medicine2010，，4： | 1 |
| 9 | Neurovascular unit permeability in neuroinflammatory diseases:a common pathologic and therapeutic target?显示文摘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. | Molly Monsour Cesar V.Borlongan | 2023 | Neural Regeneration Research2023，18，8： | 0 |
| 10 | Attenuation of amyotrophic lateral sclerosis via stem cell and extracellular vesicle therapy:An updated review显示文摘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. | Gavin Lockard Jonah Gordon Samantha Schimmel Bassel El Sayed Molly Monsour Svitlana Garbuzova-Davis Cesar V.Borlongan | 2023 | Neuroprotection2023，1，2： | 0 |
| 11 | Stem cell-derived extracellular vesicles as potential mechanism for repair of microvascular damage within and outside of the central nervous system in amyotrophic lateral sclerosis:perspective schema显示文摘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). | Svitlana Garbuzova-Davis Cesario V.Borlongan | 2021 | Neural Regeneration Research2021，16，4： | 0 |
| 12 | Traumatic brain injury treatment using a rodent model of homelessness显示文摘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). | Molly Monsour Cesar V.Borlongan | 2024 | Neural Regeneration Research2024，19，9： | 0 |
| 13 | Quite amusing stem cells:Muse cells显示文摘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. | Molly Monsour Cesar V.Borlongan | 2023 | Neural Regeneration Research2023，18，11： | 0 |
| 14 | Going straight for the gut:gut-brain axis pathology and treatment of Parkinson's disease显示文摘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. | Dominique Ebedes Cesar V.Borlongan | 2024 | Neural Regeneration Research2024，19，10： | 0 |
| 15 | Translational research in early neuroscience careers of high school students显示文摘Essentially,the knowledge of science alone offers little utility.Without 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 | Zachary M.Diamandis Nicholas S.Diaco Kelsey Duncan Marci Crowley M.Grant Liska Cesar V.Borlongan | 2017 | Neural Regeneration Research2017，12，4： | 0 |
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