Pathophysiology of Ganglioside GM1 in Ischemic Stroke: Ganglioside GM1: A Critical Review

Ganglioside GM1 is a member of the ganglioside family which has been used in many countries and is thought of as a promising alternative treatment for preventing several neurological diseases, including cerebral ischemic injury. The therapeutic effects of GM1 have been proved both in neonates and in adults following ischemic brain damage; however, its clinical efficacy in patients with ischemic stroke is still uncertain. This review examines the recent knowledge of the neuroprotective properties of GM1 in ischemic stroke, collected in the past two decades. We conclude that GM1 may have potential for stroke treatment, although we need to be cautious in respect of its complications.

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Mesenchymal Stem Cell Derived Extracellular Vesicles for Repairing the Neurovascular Unit after Ischemic Stroke

Cells ◽

10.3390/cells10040767 ◽

2021 ◽

Vol 10 (4) ◽

pp. 767

Author(s):

Courtney Davis ◽

Sean I. Savitz ◽

Nikunj Satani

Keyword(s):

Ischemic Stroke ◽

Extracellular Vesicles ◽

Neurovascular Unit ◽

Culture Conditions ◽

Therapeutic Effects ◽

Stroke Treatment ◽

Inflammatory Molecules ◽

The Brain

Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.

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Cerebral endothelial cell-derived small extracellular vesicles enhance neurovascular function and neurological recovery in rat acute ischemic stroke models of mechanical thrombectomy and embolic stroke treatment with tPA

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x21992980 ◽

2021 ◽

pp. 0271678X2199298

Author(s):

Chao Li ◽

Chunyang Wang ◽

Yi Zhang ◽

Owais K Alsrouji ◽

Alex B Chebl ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Extracellular Vesicles ◽

Mechanical Thrombectomy ◽

Infarct Volume ◽

Artery Occlusion ◽

Therapeutic Effects ◽

Vessel Occlusion ◽

Healthy Human ◽

Stroke Treatment

Treatment of patients with cerebral large vessel occlusion with thrombectomy and tissue plasminogen activator (tPA) leads to incomplete reperfusion. Using rat models of embolic and transient middle cerebral artery occlusion (eMCAO and tMCAO), we investigated the effect on stroke outcomes of small extracellular vesicles (sEVs) derived from rat cerebral endothelial cells (CEC-sEVs) in combination with tPA (CEC-sEVs/tPA) as a treatment of eMCAO and tMCAO in rat. The effect of sEVs derived from clots acquired from patients who had undergone mechanical thrombectomy on healthy human CEC permeability was also evaluated. CEC-sEVs/tPA administered 4 h after eMCAO reduced infarct volume by ∼36%, increased recanalization of the occluded MCA, enhanced cerebral blood flow (CBF), and reduced blood-brain barrier (BBB) leakage. Treatment with CEC-sEVs given upon reperfusion after 2 h tMCAO significantly reduced infarct volume by ∼43%, and neurological outcomes were improved in both CEC-sEVs treated models. CEC-sEVs/tPA reduced a network of microRNAs (miRs) and proteins that mediate thrombosis, coagulation, and inflammation. Patient-clot derived sEVs increased CEC permeability, which was reduced by CEC-sEVs. CEC-sEV mediated suppression of a network of pro-thrombotic, -coagulant, and -inflammatory miRs and proteins likely contribute to therapeutic effects. Thus, CEC-sEVs have a therapeutic effect on acute ischemic stroke by reducing neurovascular damage.

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Insight Into the Mechanisms and the Challenges on Stem Cell-Based Therapies for Cerebral Ischemic Stroke

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.637210 ◽

2021 ◽

Vol 15 ◽

Author(s):

Huiyong Liu ◽

Sydney Reiter ◽

Xiangyue Zhou ◽

Hanmin Chen ◽

Yibo Ou ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Ischemic Stroke ◽

Potential Effect ◽

Therapeutic Window ◽

Ethical Challenges ◽

Stroke Treatment ◽

Lesion Core ◽

Cerebral Ischemic Stroke ◽

Cerebral Ischemic

Strokes are the most common types of cerebrovascular disease and remain a major cause of death and disability worldwide. Cerebral ischemic stroke is caused by a reduction in blood flow to the brain. In this disease, two major zones of injury are identified: the lesion core, in which cells rapidly progress toward death, and the ischemic penumbra (surrounding the lesion core), which is defined as hypoperfusion tissue where cells may remain viable and can be repaired. Two methods that are approved by the Food and Drug Administration (FDA) include intravenous thrombolytic therapy and endovascular thrombectomy, however, the narrow therapeutic window poses a limitation, and therefore a low percentage of stroke patients actually receive these treatments. Developments in stem cell therapy have introduced renewed hope to patients with ischemic stroke due to its potential effect for reversing the neurological sequelae. Over the last few decades, animal tests and clinical trials have been used to treat ischemic stroke experimentally with various types of stem cells. However, several technical and ethical challenges must be overcome before stem cells can become a choice for the treatment of stroke. In this review, we summarize the mechanisms, processes, and challenges of using stem cells in stroke treatment. We also discuss new developing trends in this field.

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Reflection on the Past, Present, and Future of Thrombolytic Therapy for Acute Ischemic Stroke

Neurology ◽

10.1212/wnl.0000000000012806 ◽

2021 ◽

Vol 97 (20 Supplement 2) ◽

pp. S170-S177

Author(s):

Stacie L. Demel ◽

Robert Stanton ◽

Yasmin N. Aziz ◽

Opeolu Adeoye ◽

Pooja Khatri

Keyword(s):

Ischemic Stroke ◽

Thrombolytic Therapy ◽

Acute Ischemic Stroke ◽

Ct Perfusion ◽

Critical Role ◽

Recombinant Tissue Plasminogen Activator ◽

Initial Time ◽

Stroke Treatment ◽

The Past ◽

Therapeutic Landscape

More than 25 years have passed since the US Food and Drug Administration approved IV recombinant tissue plasminogen activator (alteplase) for the treatment of acute ischemic stroke. This landmark decision brought a previously untreatable disease into a new therapeutic landscape, providing inspiration for clinicians and hope to patients. Since that time, the use of alteplase in the clinical setting has become standard of care, continually improving with quality measures such as door-to-needle times and other metrics of specialized stroke unit care. The past decade has seen more widespread use of alteplase in the prehospital setting with mobile stroke units and telestroke and beyond initial time windows via the use of CT perfusion or MRI. Simultaneously, the position of alteplase is being challenged by new lytics and by the concept of its bypass altogether in the era of endovascular therapy. We provide an overview of alteplase, including its earliest trials and how they have shaped the current therapeutic landscape of ischemic stroke treatment, and touch on new frontiers for thrombolytic therapy. We highlight the critical role of thrombolytic therapy in the past, present, and future of ischemic stroke care.

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Abstract 158: Pre-existing Cancer Exacerbates Cerebral Ischemic Stroke in Mice via Regulatory T Cell Redistribution

Stroke ◽

10.1161/str.48.suppl_1.158 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Long Wang ◽

Yuxi Zhou ◽

Weifeng Yu ◽

Peiying Li

Keyword(s):

Colon Cancer ◽

Ischemic Stroke ◽

Immune Cell ◽

Infarct Volume ◽

Ischemic Brain Injury ◽

Stroke Patients ◽

Ischemic Brain ◽

Cerebral Ischemic Stroke ◽

Neuro Inflammation ◽

Cerebral Ischemic

Background and purpose: Accumulating epidemic evidence suggest that a considerable number of ischemic stroke patients had 1 or more cancer diagnosis before stroke attack. How the pre-existing cancer impact the cerebral ischemic injury is remarkably unknown. We tested the hypothesis that pre-existing cancer exacerbates cerebral ischemic stroke via regulatory T cell (Treg) redistribution. Methods: MC38 colon cancer cells or B16 melanoma cells were injected subcutaneously at the dose of 5*10 5 cells in 200μl PBS 3 weeks before distal middle cerebral artery occlusion (d-MCAO) surgery. Infarct volume was assessed at 3 days after surgery by staining the mice brain with 2,3,5-triphenyltetrazolium chloride. Sensorimotor assessments, such as body proprioception, climbing, forelimb walking, lateral turning, foot fault and adhesive removal were examined at 3, 5, 7, 14, 21 and 28 days after stroke. Neuro-inflammation was examined by measuring inflammatory cytokines with RT-PCR and immune cell infiltration using immunofluorescence and flow cytometry. Results: Pre-existing colon cancer and melanoma both exacerbated infarct volume growth in d-MCAO mice at 3 days after surgery. Mice with colon cancer exhibited prominently deterioration in their performance in sensorimotor functions after stroke compared with mice without cancer. Pre-existing colon cancer augmented peripheral immune cell infiltration into the ischemic brain but hindered Tregs’ recruitment into the brain. Cerebral ischemic stroke induced reduction in the number of Tregs in the peripheral blood were significantly aggravated in mice with pre-existing colon cancer. Depletion of Tregs with CD25 monoclonal antibody increased infarct volume in stroke mice but did not further exacerbate infarct growth in colon cancer stroke mice. Conclusion: Pre-existing cancer exacerbates ischemic brain injury and neuro-inflammation after stroke. Tregs redistribution plays an indispensable role in the cancer related deterioration of ischemic brain injury and may represent a promising target for treating stroke patients with pre-existing cancer.

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Multiplex Brain Proteomic Analysis Revealed the Molecular Therapeutic Effects of Buyang Huanwu Decoction on Cerebral Ischemic Stroke Mice

PLoS ONE ◽

10.1371/journal.pone.0140823 ◽

2015 ◽

Vol 10 (10) ◽

pp. e0140823 ◽

Cited By ~ 20

Author(s):

Hong-Jhang Chen ◽

Yuh-Chiang Shen ◽

Young-Ji Shiao ◽

Kuo-Tong Liou ◽

Wei-Hsiang Hsu ◽

...

Keyword(s):

Ischemic Stroke ◽

Proteomic Analysis ◽

Therapeutic Effects ◽

Buyang Huanwu Decoction ◽

Cerebral Ischemic Stroke ◽

Cerebral Ischemic ◽

Molecular Therapeutic

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Thrombolysis and Mechanical Thrombectomy as Leading Treatments for Acute Ischemic Stroke

The Journal of Neurological and Neurosurgical Nursing ◽

10.15225/pnn.2019.8.4.6 ◽

2019 ◽

Vol 8 (4) ◽

pp. 177-181

Author(s):

Karolina Filipska ◽

◽

Adam Wiśniewski ◽

Robert Ślusarz ◽

◽

...

Keyword(s):

Ischemic Stroke ◽

Mechanical Thrombectomy ◽

Impact Load ◽

Vascular Diseases ◽

Stroke Treatment ◽

The Past ◽

Key Words Ischemic Stroke ◽

Successful Recovery ◽

The World ◽

The Impact

Brain vascular diseases, especially strokes, are still a very serious public health and medicine problem. The world is still facing an epidemic of stroke. With the impact load increasing all over the world, there is a continuing need to understand the characteristics of this disease and its impact in different countries. Despite significant improvements in primary prevention and treatment efficacy over the past decades, stroke is still a debilitating disease. Early treatment is the key to successful recovery of patients with ischemic stroke. The aim of the study is to show the most effective methods of treating patients in the acute phase of ischemic stroke. (JNNN 2019;8(4):177–181) Key Words: ischemic stroke, treatment, thrombolysis, thrombectomy

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Potential Role of Exosomes in Ischemic Stroke Treatment

Biomolecules ◽

10.3390/biom12010115 ◽

2022 ◽

Vol 12 (1) ◽

pp. 115

Author(s):

Lingling Jiang ◽

Weiqi Chen ◽

Jinyi Ye ◽

Yilong Wang

Keyword(s):

Ischemic Stroke ◽

Positive Impact ◽

Current Knowledge ◽

Therapeutic Effects ◽

Stroke Treatment ◽

Neuroprotective Drugs ◽

Life Threatening ◽

Low Toxicity ◽

Neurovascular Remodeling

Ischemic stroke is a life-threatening cerebral vascular disease and accounts for high disability and mortality worldwide. Currently, no efficient therapeutic strategies are available for promoting neurological recovery in clinical practice, except rehabilitation. The majority of neuroprotective drugs showed positive impact in pre-clinical studies but failed in clinical trials. Therefore, there is an urgent demand for new promising therapeutic approaches for ischemic stroke treatment. Emerging evidence suggests that exosomes mediate communication between cells in both physiological and pathological conditions. Exosomes have received extensive attention for therapy following a stroke, because of their unique characteristics, such as the ability to cross the blood brain–barrier, low immunogenicity, and low toxicity. An increasing number of studies have demonstrated positively neurorestorative effects of exosome-based therapy, which are largely mediated by the microRNA cargo. Herein, we review the current knowledge of exosomes, the relationships between exosomes and stroke, and the therapeutic effects of exosome-based treatments in neurovascular remodeling processes after stroke. Exosomes provide a viable and prospective treatment strategy for ischemic stroke patients.

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Abstract 57: Brain-heart Interaction: Age Aggravates Cardiac Damage After Cerebral Ischemic Stroke

Stroke ◽

10.1161/str.48.suppl_1.57 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Zhili Chen ◽

Tao Yan ◽

Qiang Zhao ◽

Yi Shen ◽

Wei Li ◽

...

Keyword(s):

Ischemic Stroke ◽

Young Adult ◽

Cardiac Dysfunction ◽

Middle Age ◽

Neurological Diseases ◽

Left Ventricular ◽

Middle Aged ◽

Transthoracic Doppler Echocardiography ◽

Cerebral Ischemic Stroke ◽

Cerebral Ischemic

Background: The incidence of cardiovascular diseases is approximately three times higher in patients with neurological diseases than in patients without neurological diseases. Clinical findings have demonstrated that 70% of stroke patients exhibit cardiac dysfunction. Myocardial injury may occur after stroke in the absence of primary cardiac causes. In this study, we tested the hypothesis that age affects brain-heart interaction after cerebral ischemic stroke, and that aging increases cardiac dysfunction after stroke. Methods: Young adult (2-3 months), middle age (8-9 months) and aged (17-18 months) male C57BL mice were subjected to distal middle cerebral artery occlusion (dMCAo) or sham control (n=10/group). Cardiac hemodynamics and function were measured by transthoracic Doppler echocardiography. Mice were sacrificed at 28 days after surgery. Immunostaining of heart tissues were performed. To elucidate the mechanisms of stroke mediated cardiac dysfunction, heart tissue flow cytometry was employed to measure myocardial inflammation at 4 days after stroke in middle aged mice (n=6/group). Results: 1) Stroke mice exhibited an age dependent decrease in cardiac function: Stroke in young adult mice induced mild cardiac dysfunction; While the middle age and aged stroke mice exhibited significantly increased cardiac dysfunction compared to age matched sham controls, respectively (p<0.05). Middle age stroke mice exhibit significantly decreased ejection fraction (EF), and increased left ventricular systolic volume (LVVOLs) and LV volume during diastole (LVVOLd); Aged stroke mice exhibited significantly decreased EF and fractional shortening, increased LVVOLs LVVOLd, LV end-diastolic and end-systolic diameter, when compared to age matched sham controls, respectively. 2) Middle age and aged stroke mice exhibited significantly increased myocyte hypertrophy and fibrosis measured by Sirius red collagen staining. 3) Middle aged stroke mice exhibited significantly increased CD45 and CD11b high /CD45 + inflammation cell infiltration in the heart compared to middle age sham controls. Conclusion: Stroke induces cardiac dysfunction. Age affects brain-heart interaction, and age aggravates heart damage after cerebral ischemic stroke.

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Long Course Hyperbaric Oxygen Stimulates Neurogenesis and Attenuates Inflammation after Ischemic Stroke

Mediators of Inflammation ◽

10.1155/2013/512978 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 27

Author(s):

Ying-Sheng Lee ◽

Chung-Ching Chio ◽

Ching-Ping Chang ◽

Liang-Chao Wang ◽

Po-Min Chiang ◽

...

Keyword(s):

Ischemic Stroke ◽

Hyperbaric Oxygen ◽

Artery Occlusion ◽

Trophic Factors ◽

Therapeutic Effects ◽

Ischemic Brain ◽

Neurological Severity Score ◽

Group Mobilization ◽

Long Course ◽

Cerebral Artery Occlusion

Several studies have provided evidence with regard to the neuroprotection benefits of hyperbaric oxygen (HBO) therapy in cases of stroke, and HBO also promotes bone marrow stem cells (BMSCs) proliferation and mobilization. This study investigates the influence of HBO therapy on the migration of BMSCs, neurogenesis, gliosis, and inflammation after stroke. Rats that sustained transient middle cerebral artery occlusion (MCAO) were treated with HBO three weeks or two days. The results were examined using a behavior test (modified neurological severity score, mNSS) and immunostaining to evaluate the effects of HBO therapy on migration of BMSCs, neurogenesis, and gliosis, and expression of neurotrophic factors was also evaluated. There was a lower mNSS score in the three-week HBO group when compared with the two-day HBO group. Mobilization of BMSCs to an ischemic area was more improved in long course HBO treatments, suggesting the duration of therapy is crucial for promoting the homing of BMSCs to ischemic brain by HBO therapies. HBO also can stimulate expression of trophic factors and improve neurogenesis and gliosis. These effects may help in neuronal repair after ischemic stroke, and increasing the course of HBO therapy might enhance therapeutic effects on ischemic stroke.

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