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A Novel Rat Model of Embolic Cerebral Ischemia Using a Cell-Implantable Radiopaque Hydrogel Microfiber
We present a novel rat model of focal infarct restricted to the middle cerebral artery territory using a radiopaque hydrogel microfiber positioned under fluoroscopic guidance. By comparing the use of stem cell-containing versus non-containing fibers in this stroke model, it would be possible to determine the efficacy of"pure" cell transplantation in treating stroke.
Source: Translational Stroke Research - March 3, 2023 Category: Neurology Source Type: research

Association of Gut Microbiome with Early Brain Injury After Subarachnoid Hemorrhage: an Experimental Study
AbstractThe occurrence of early brain injury (EBI) following subarachnoid hemorrhage (SAH) is crucial in the prognosis of SAH; however, no effective treatment for EBI has been developed. Gut microbiome (GM) composition influences the outcome of various diseases, including ischemic stroke. Here, we evaluated whether prior GM alteration could prevent EBI following SAH. We altered the GM of 7-week-old male rats by administering antibiotic-containing water for 2  weeks and performing fecal microbiome transplantation after antibiotic induction. Composition of the GM was profiled using 16S rRNA. We induced SAH by injecting bloo...
Source: Translational Stroke Research - December 9, 2022 Category: Neurology Source Type: research

Endogenous Neural Stem Cell –induced Neurogenesis after Ischemic Stroke: Processes for Brain Repair and Perspectives
AbstractIschemic stroke is a very common cerebrovascular accident that occurred in adults and causes higher risk of neural deficits. After ischemic stroke, patients are often left with severe neurological deficits. Therapeutic strategies for ischemic stroke might mitigate neuronal loss due to delayed neural cell death in the penumbra or seek to replace dead neural cells in the ischemic core. Currently, stem cell therapy is the most promising approach for inducing neurogenesis for neural repair after ischemic stroke. Stem cell treatments include transplantation of exogenous stem cells but also stimulating endogenous neural ...
Source: Translational Stroke Research - September 3, 2022 Category: Neurology Source Type: research

Transplantation of Exercise-Induced Extracellular Vesicles as a Promising Therapeutic Approach in Ischemic Stroke
AbstractClinical evidence affirms physical exercise is effective in preventive and rehabilitation approaches for ischemic stroke. This sustainable efficacy is independent of cardiovascular risk factors and associates substantial reprogramming in circulating extracellular vesicles (EVs). The intricate journey of pluripotent exercise-induced EVs from parental cells to the whole-body and infiltration to cerebrovascular entity offers several mechanisms to reduce stroke incidence and injury or accelerate the subsequent recovery. This review delineates the potential roles of EVs as prospective effectors of exercise. The candidat...
Source: Translational Stroke Research - May 21, 2022 Category: Neurology Source Type: research

Neural Stem Cells Therapy for Ischemic Stroke: Progress and Challenges
AbstractIschemic stroke, with its high morbidity and mortality, is the most common cerebrovascular accident and results in severe neurological deficits. Despite advances in medical and surgical intervention, post-stroke therapies remain scarce, which seriously affects the quality of life of patients. Over the past decades, stem cell transplantation has been recognized as very promising therapy for neurological diseases. Neural stem cell (NSC) transplantation is the optimal choice for ischemic stroke as NSCs inherently reside in the brain and can potentially differentiate into a variety of cell types within the central nerv...
Source: Translational Stroke Research - January 15, 2022 Category: Neurology Source Type: research

Bone Marrow-Derived Alk1 Mutant Endothelial Cells and Clonally Expanded Somatic Alk1 Mutant Endothelial Cells Contribute to the Development of Brain Arteriovenous Malformations in Mice
AbstractWe have previously demonstrated that deletion of activin receptor-like kinase 1 (Alk1) or endoglin in a fraction of endothelial cells (ECs) induces brain arteriovenous malformations (bAVMs) in adult mice upon angiogenic stimulation. Here, we addressed three related questions: (1) couldAlk1− mutant bone marrow (BM)-derived ECs (BMDECs) cause bAVMs? (2) is Alk1− ECs clonally expended during bAVM development? and (3) is the number of mutant ECs correlates to bAVM severity? For the first question, we transplanted BM fromPdgfbiCreER;Alk12f/2f mice (EC-specific tamoxifen-inducible Cre withAlk1-floxed alleles) into wi...
Source: Translational Stroke Research - October 21, 2021 Category: Neurology Source Type: research

Mitochondrial Transfer as a Therapeutic Strategy Against Ischemic Stroke
AbstractStroke is a debilitating disease that remains the second leading cause of death and disability worldwide. Despite accumulating knowledge of the disease pathology, treatments for stroke are limited, and clinical translation of the neuroprotective agents has not been a complete success. Accumulating evidence links mitochondrial dysfunction to brain impairments after stroke. Recent studies have implicated the important roles of healthy mitochondria in neuroprotection and neural recovery following ischemic stroke. New and convincing studies have shown that mitochondrial transfer to the damaged cells can help revive cel...
Source: Translational Stroke Research - June 25, 2020 Category: Neurology Source Type: research

Adenosine A 2A Receptors in Bone Marrow-Derived Cells Attenuate Cognitive Impairment in Mice After Chronic Hypoperfusion White Matter Injury
AbstractThe mechanism of cognitive dysfunction caused by ischemic white matter lesions is unclear. To explore the effect and mechanism of different cell-derived adenosine A2A receptor (A2AR) in cognitive impairment caused by chronic hypoperfusion white matter lesions (CHWMLs), we destroyed the bone marrow hematopoietic capacity of the recipient mice using radiation irradiation followed by establishing the selectively inactivated or reconstituted A2AR models with the transplanting bone marrow from global A2AR gene knockout or wild-type mice into wild-type or gene knockout mice, respectively. Then Morris Water Maze (MWM), EL...
Source: Translational Stroke Research - May 10, 2020 Category: Neurology Source Type: research

p5 Peptide-Loaded Human Adipose-Derived Mesenchymal Stem Cells Promote Neurological Recovery After Focal Cerebral Ischemia in a Rat Model
In conclusion, administration of hADMSC-loaded p5 peptide to post-stroke rats created conditions that supported survival of drug-loaded hADMSCs after cerebral ischemia, suggesting its therapeutic potential in patients with stroke.
Source: Translational Stroke Research - May 5, 2020 Category: Neurology Source Type: research

Cerebral Organoids Repair Ischemic Stroke Brain Injury
AbstractStroke is the second leading cause of death and main cause of disability worldwide, but with few effective therapies. Although stem cell-based therapy has been proposed as an exciting regenerative medicine strategy for brain injury, there are limitations. The developed cerebral organoids (COs) represent a promising transplantation source for stroke that remains to be answered. Here, we transplanted COs at 55  days and explored the feasibility in the rat middle cerebral artery occlusion (MCAO) model of stroke. COs transplantation at 6 h or even 24 h after MCAO significantly reduces brain infarct volume and improv...
Source: Translational Stroke Research - December 29, 2019 Category: Neurology Source Type: research

Transplantation of Directly Reprogrammed Human Neural Precursor Cells Following Stroke Promotes Synaptogenesis and Functional Recovery
AbstractStroke is one of the leading causes of long-term disability. Cell transplantation is a promising strategy to treat stroke. We explored the efficacy of directly reprogrammed human neural precursor cell (drNPC) transplants to promote functional recovery in a model of focal ischemic stroke in the mouse sensorimotor cortex. We show that drNPCs express neural precursor cell markers and are neurally committed at the time of transplantation. Mice that received drNPC transplants recovered motor function, irrespective of transplant vehicle or recipient sex, and with no correlation to lesion volume or glial scarring. The maj...
Source: Translational Stroke Research - February 12, 2019 Category: Neurology Source Type: research

Hydrogel Scaffolds: Towards Restitution of Ischemic Stroke-Injured Brain
AbstractChronic brain injury following cerebral ischemia is a severe debilitating neurological condition, where clinical intervention is well known to decrease morbidity and mortality. Despite the development of several therapeutic strategies, clinical outcome in the majority of patients could be better improved, since many still face life-long neurological deficits. Among the several strategic options that are currently being pursued, tissue engineering provides much promise for neural tissue salvage and regeneration in brain ischemia. Specifically, hydrogel biomaterials have been utilized to docket biomolecules, adhesion...
Source: Translational Stroke Research - August 27, 2018 Category: Neurology Source Type: research

Intrathecal Injection of Allogenic Bone Marrow-Derived Mesenchymal Stromal Cells in Treatment of Patients with Severe Ischemic Stroke: Study Protocol for a Randomized Controlled Observer-Blinded Trial
AbstractMesenchymal stromal cells (MSCs) can differentiate into multiple tissues. Preclinical studies have shown that MSC-based therapy is a potential new treatment approach for ischemic stroke. These results support the urgent need for further studies of MSC transplantation in the treatment of ischemic stroke in humans. Here, we develop a prospective, randomized, controlled, observer-blinded phase II trial to assess the clinical safety, feasibility, and therapeutic mechanisms of allogenic bone marrow-derived MSCs (BM-MSCs) by intrathecal infusion in the treatment of patients with cerebral infarction within the middle cere...
Source: Translational Stroke Research - May 23, 2018 Category: Neurology Source Type: research

Cell Therapy in Stroke —Cautious Steps Towards a Clinical Treatment
AbstractIn the future, stroke patients may receive stem cell therapy as this has the potential to restore lost functions. However, the development of clinically deliverable therapy has been slower and more challenging than expected. Despite recommendations by STAIR and STEPS consortiums, there remain flaws in experimental studies such as lack of animals with comorbidities, inconsistent approaches to experimental design, and concurrent rehabilitation that might lead to a bias towards positive results. Clinical studies have typically been small, lacking control groups as well as often without clear biological hypotheses to g...
Source: Translational Stroke Research - November 17, 2017 Category: Neurology Source Type: research

Biomaterials for Enhancing CNS Repair
Abstract The health of the central nervous system (CNS) does not only rely on the state of the neural cells but also on how various extracellular components organize cellular behaviors into proper tissue functions. Biomaterials have been valuable in restoring or augmenting the roles of extracellular components in the CNS in the event of injury and disease. In this review, we highlight how biomaterials have been enabling tools in important therapeutic strategies involving cell transplantation and drug/protein delivery. We further discuss advances in biomaterial design and applications that can potentially be transl...
Source: Translational Stroke Research - May 31, 2016 Category: Neurology Source Type: research

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