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Risk of New-onset Stroke in Patients with Type 2 Diabetes with Chronic Kidney Disease on Sodium-glucose Co-transporter-2 Inhibitor Users
This study aimed to examine the association between the use of SGLT2 inhibitors and NOS risk in patients with T2D and CKD. We conducted a nationwide retrospective cohort study using data from the Taiwan Health Insurance Review and Assessment Service database for the years 2004 to 2019. The primary outcome was the risk of incident stroke, which was estimated using hazard ratios (HRs) and 95% confidence intervals (CIs). We used multiple Cox regression modeling to analyze the association between SGLT2 inhibitor use and the risk of stroke in patients with T2D and CKD. In a cohort of 113,710 patients with T2D and CKD who were u...
Source: Translational Stroke Research - July 14, 2023 Category: Neurology Source Type: research

Gut Microbiota in Ischemic Stroke: Role of Gut Bacteria-Derived Metabolites
AbstractIschemic stroke (IS) remains a leading cause of death and long-term disability globally. Several mechanisms including glutamate excitotoxicity, calcium overload, neuroinflammation, oxidative stress, mitochondrial damage, and apoptosis are known to be involved in the pathogenesis of IS, but the underlying pathophysiology mechanisms of IS are not fully clarified. During the past decade, gut microbiota were recognized as a key regulator to affect the health of the host either directly or via their metabolites. Recent studies indicate that gut bacterial dysbiosis is closely related to hypertension, diabetes, obesity, d...
Source: Translational Stroke Research - October 24, 2022 Category: Neurology Source Type: research

High-Dose Vitamin C Prevents Secondary Brain Damage After Stroke via Epigenetic Reprogramming of Neuroprotective Genes
AbstractVitamin C has recently been identified as an epigenetic regulator by activating ten-eleven translocases (TETs), enzymes involved in generating DNA hydroxymethylcytosine (5hmC). Currently, we investigated whether high-dose vitamin C promotes neuroprotection through epigenetic modulation of 5hmC, if there are sex-specific differences in outcome, and the therapeutic potential of vitamin C in stroke-related comorbidities in adult mice. Post-stroke treatment with ascorbate (reduced form), but not dehydroascorbate (oxidized form), increased TET3 activity and 5hmC levels and reduced infarct following focal ischemia. Hydro...
Source: Translational Stroke Research - March 20, 2022 Category: Neurology Source Type: research

Delayed rFGF21 Administration Improves Cerebrovascular Remodeling and White Matter Repair After Focal Stroke in Diabetic Mice
This study aims to evaluate the potential effects of rFGF21 on cerebrovascular remodeling after T2DM stroke. Permanent distal middle cerebral artery occlusion was performed in heterozygous non-diabetic db/  + and homozygous diabetic db/db mice. Daily rFGF21 administration was initiated 1 week after stroke induction and maintained for up to 2 weeks thereafter. Multiple markers associated with post-stroke recovery, including angiogenesis, oligodendrogenesis, white matter integrity, and neurogenesi s, were assessed up to 3 weeks after stroke. Our results showed an impairment in post-stroke vascular remodeling under T2D...
Source: Translational Stroke Research - March 14, 2022 Category: Neurology Source Type: research

Diabetes Mellitus/Poststroke Hyperglycemia: a Detrimental Factor for tPA Thrombolytic Stroke Therapy
AbstractIntravenous administration of tissue-type plasminogen activator (IV tPA) therapy has long been considered a mainstay in ischemic stroke management. However, patients respond to IV tPA therapy unequally with some subsets of patients having worsened outcomes after treatment. In particular, diabetes mellitus (DM) is recognized as a clinically important vascular comorbidity that leads to lower recanalization rates and increased risks of hemorrhagic transformation (HT). In this short-review, we summarize the recent advances in understanding of the underlying mechanisms involved in post-IV tPA worsening of outcome in dia...
Source: Translational Stroke Research - April 20, 2021 Category: Neurology Source Type: research

CYP2C19 Loss-of-Function Associated with First-Time Ischemic Stroke in Non-surgical Asymptomatic Carotid Artery Stenosis During Clopidogrel Therapy
This study measures effect ofCYP2C19 genotype on ischemic stroke risk during clopidogrel therapy for asymptomatic, extracranial carotid stenosis patients. Using deidentified electronic health records, patients were selected for retrospective cohort using administrative code for carotid stenosis, availability ofCYP2C19 genotype result, clopidogrel exposure, and established patient care. Patients with intracranial atherosclerosis, aneurysm, arteriovenous malformation, prior ischemic stroke, or observation time<1 month were excluded. Dual antiplatelet therapy patients were included. Patients with carotid endarterectomy or ...
Source: Translational Stroke Research - February 21, 2021 Category: Neurology Source Type: research

Deferoxamine Treatment Prevents Post-Stroke Vasoregression and Neurovascular Unit Remodeling Leading to Improved Functional Outcomes in Type 2 Male Diabetic Rats: Role of Endothelial Ferroptosis
This study aimed to determine the impact of iron chelation with deferoxamine (DFX) on (1) cerebral vascularization patterns and (2) functional outcomes after stroke in control and diabetic rats. After 8  weeks of type 2 diabetes induced by a combination of high-fat diet and low-dose streptozotocin, male control and diabetic animals were subjected to thromboembolic middle cerebral artery occlusion (MCAO) and randomized to vehicle, DFX, or tPA/DFX and followed for 14 days with behavioral tests. Vas cular indices (vascular volume and surface area), neurovascular remodeling (AQP4 polarity), and microglia activation were meas...
Source: Translational Stroke Research - August 31, 2020 Category: Neurology Source Type: research

Endogenous Regulatory T Cells Promote M2 Macrophage Phenotype in Diabetic Stroke as Visualized by Optical Imaging
AbstractRegulatory T cells (Tregs) play an immunosuppressive role in various diseases, yet their function remains controversial in stroke and obscure in diabetic stroke. In the present study, Tregs were found downregulated in the peripheral blood of type 2 diabetes mellitus (T2DM) stroke models and patients compared with controls. In ischemic stroke mice (both T2DM and wild type), endogenous Tregs boosted by CD28SA increased CD206+ M2 macrophage/microglia cells, decreased infarct volumes, and improved neurological recovery. Our results demonstrated the potential of boosting Tregs for treating T2DM stroke. Furthermore, we u...
Source: Translational Stroke Research - April 1, 2020 Category: Neurology Source Type: research

CD133+Exosome Treatment Improves Cardiac Function after Stroke in Type 2 Diabetic Mice
In this study, we tested whether treatment with exosomes harvested from human umbilical cord blood derived CD133+ cells (CD133+Exo) improves cardiac function in type 2 diabetes mellitus (T2DM) stroke mice. Adult (3 –4 m), male, BKS.Cg-m+/+Leprdb/J (db/db, T2DM) and non-DM (db+) mice were randomized to sham or photothrombotic stroke groups. T2DM-stroke mice were treated with phosphate-buffered saline (PBS) or CD133+Exo (20  μg, i.v.) at 3 days after stroke. T2DM sham and T2DM+CD133+Exo treatment groups were included as controls. Echocardiography was performed, and mice were sacrificed at 28 days after stroke. Cardiom...
Source: Translational Stroke Research - March 19, 2020 Category: Neurology Source Type: research

Delayed Administration of Angiotensin II Type 2 Receptor (AT2R) Agonist Compound 21 Prevents the Development of Post-stroke Cognitive Impairment in Diabetes Through the Modulation of Microglia Polarization
AbstractA disabling consequence of stroke is cognitive impairment, occurring in 12% –48% of patients, for which there is no therapy. A critical barrier is the lack of understanding of how post-stroke cognitive impairment (PSCI) develops. While 70% of stroke victims present with comorbid diseases such as diabetes and hypertension, the limited use of comorbid disease models in prec linical research further contributes to this lack of progress. To this end, we used a translational model of diabetes to study the development of PSCI. In addition, we evaluated the application of compound 21 (C21), an angiotensin II Type 2 rece...
Source: Translational Stroke Research - December 2, 2019 Category: Neurology Source Type: research

Association Between Systemic Inflammation, Carotid Arteriosclerosis, and Autonomic Dysfunction
In conclusion, systemic inflammation is associated with carotid rather than with generalized arteriosclerotic disease. The association between systemic inflammation and carotid arteriosclerosis is mediated by a reduction in vagal tone which indicates a major role of carotid arteriosclerosis-mediated autonomic dysfunction in the pathogenesis of systemic inflammation in arteriosclerotic disease.
Source: Translational Stroke Research - May 15, 2019 Category: Neurology Source Type: research

Very Low Frequency Heart Rate Variability Predicts the Development of Post-Stroke Infections
AbstractStroke-induced immunodepression is a major risk factor for severe infectious complications in the immediate post-stroke period. We investigated the predictive value of heart rate variability (HRV) to identify patients at risk of post-stroke infection, systemic inflammatory response syndrome, or severe sepsis during the post-acute interval from days 3 to 5 after stroke onset. A prospective, observational monocentric cohort study was conducted in a university hospital stroke unit of patients with ischemic infarction in the territory of the middle cerebral artery without an ongoing infection at admission. Standard HRV...
Source: Translational Stroke Research - January 7, 2019 Category: Neurology Source Type: research

Inhibition of VEGF Signaling Reduces Diabetes-Exacerbated Brain Swelling, but Not Infarct Size, in Large Cerebral Infarction in Mice
This study suggests consideration of stroke therapies aiming at primarily reducing brain swelling for subjects with diabetes.
Source: Translational Stroke Research - October 1, 2018 Category: Neurology Source Type: research

MMP10 Promotes Efficient Thrombolysis After Ischemic Stroke in Mice with Induced Diabetes
AbstractDiabetes is an important risk factor for ischemic stroke (IS). Tissue-type plasminogen activator (tPA) has been associated with less successful revascularization and poor functional outcome in diabetes. We assessed whether a new thrombolytic strategy based on MMP10 was more effective than tPA in a murine IS model of streptozotocin (STZ)-induced diabetes. Wild-type mice were administered a single dose of streptozotocin (STZ) (180  mg/kg) to develop STZ-induced diabetes mellitus. Two weeks later, IS was induced by thrombin injection into the middle cerebral artery and the effect of recombinant MMP10 (6.5 μg/kg), t...
Source: Translational Stroke Research - July 27, 2018 Category: Neurology Source Type: research

Genetic and Environmental Contributions to Variation in the Posterior Communicating Collaterals of the Circle of Willis
AbstractVariation in blood flow mediated by the posterior communicating collateral arteries (PComs) contributes to variation in the severity of tissue injury in obstructive disease. Evidence in animals and humans indicates that differences in the extent of PComs, i.e., their anatomic lumen diameter and whether they are present bilaterally, unilaterally, or absent, are a major factor. These differences arise during development since they are present at birth. However, the causal mechanisms are unknown. We used angiography after maximal dilation to examine involvement of genetic, environmental, and stochastic factors. The ex...
Source: Translational Stroke Research - March 27, 2018 Category: Neurology Source Type: research

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