scholarly journals Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Grissi ◽  
Cédric Boudot ◽  
Maryam Assem ◽  
Alexandre Candellier ◽  
Mathilde Lando ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Ischemic Stroke ◽  
Kidney Disease ◽  
Brain Activity ◽  
Artery Occlusion ◽  
Diabetic Patients ◽  
Stroke Severity ◽  
Neurological Score ◽  
Amp Activated Protein Kinase ◽  
Cerebral Artery Occlusion

AbstractChronic kidney disease (CKD) worsens ischemic stroke severity in both patients and animals. In mice, these poorer functional outcomes are associated with decreased brain activity of AMP-activated protein kinase (AMPK), a molecule that recently emerged as a potential therapeutic target for ischemic stroke. The antidiabetic drug metformin, a well-known activator of AMPK, has improved stroke outcomes in diabetic patients with normal renal function. We investigated whether chronic metformin pre-conditioning can rescue AMPK activity and prevent stroke damage in non-diabetic mice with CKD. Eight-week-old female C57BL/6J mice were assigned to CKD or SHAM groups. CKD was induced through right kidney cortical electrocautery, followed by left total nephrectomy. Mice were then allocated to receive metformin (200 mg/kg/day) or vehicle for 5 weeks until stroke induction by transient middle cerebral artery occlusion (tMCAO). The infarct volumes were lower in CKD mice exposed to metformin than in vehicle-treated CKD mice 24 h after tMCAO. Metformin pre-conditioning of CKD mice improved their neurological score, grip strength, and prehensile abilities. It also enhanced AMPK activation, reduced apoptosis, increased neuron survival and decreased microglia/macrophage M1 signature gene expression as well as CKD-induced activation of the canonical NF-κB pathway in the ischemic lesions of CKD mice.

scholarly journals Cellular and molecular mechanisms associated with ischemic stroke severity in female mice with chronic kidney disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lucie Hénaut ◽  
Maria Grissi ◽  
François Brazier ◽  
Maryam Assem ◽  
Sabrina Poirot-Leclercq ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Ischemic Stroke ◽  
Kidney Disease ◽  
Molecular Mechanisms ◽  
Stroke Severity ◽  
Female Mice

scholarly journals Sphingosine 1-phosphate, a Novel TREM2 Ligand, Promotes Phagocytosis and Reduce Ischemic Injury

2020 ◽  
Author(s):  
Xiu-Lan Sun ◽  
Teng-Fei Xue ◽  
Juan Ji ◽  
Ruo-Bing Guo ◽  
Yu-Qin Sun ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Infarct Volume ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Endogenous Ligand ◽  
Microglial Phagocytosis ◽  
Neurological Score ◽  
Cellular Debris ◽  
Sphingosine 1 Phosphate ◽  
Cerebral Artery Occlusion

Abstract Background: Activation of TREM2 protects against brain injury in ischemic stroke via immunoregulation. However, the endogenous ligand of TREM2 remains unknown. Here, we tested the hypothesis that S1P, an immunoregulator, functions as TREM2 ligand to promote microglial phagocytosis.Methods: SD rats, C57BL/6J mice and TREM2-/- mice were subjected to transient middle cerebral artery occlusion, and primary microglia were subjected to oxygen-glucose deprivation. Phagocytosis was investigated via immunofluorescence and two-photon microscope. LC-MS/MS, microscale thermophoresis and surface plasmon resonance were used to confirm the TREM2-S1P interaction.Results: FTY720, an analog of S1P, promoted microglial phagocytosis in ischemic stroke independent of S1PRs expressed on microglia. S1P was confirmed to be a novel endogenous ligand for TREM2 and promote cellular debris clearance. The enhanced cellular debris clearance ameliorated neurological score and infarct volume, relying on TREM2. Moreover, FTY720 was demonstrated to promote hemoglobin clearance in intracerebral hemorrhage and ameliorate hemorrhagic injury.Conlusions: The present work reveals for the first time that S1P acts as a novel endogenous ligand of TREM2 to effectively promote microglial phagocytosis, and provides a new lead compound for developing TREM2 modulator.

scholarly journals Association of lipid profiles with severity and outcome of acute ischemic stroke in patients with and without chronic kidney disease

2020 ◽  
Author(s):  
Ailing Zhang ◽  
Wenjing Deng ◽  
Bin Zhang ◽  
Mengyang Ren ◽  
Long Tian ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Ischemic Stroke ◽  
Kidney Disease ◽  
Acute Ischemic Stroke ◽  
Lipid Profiles ◽  
Stepwise Logistic Regression ◽  
Stroke Severity ◽  
Severe Stroke ◽  
Adjusted Risk ◽  
Lipid Components

Abstract Background Contribution of lipid profiles to stroke severity and outcome was inconclusive, whether chronic kidney disease (CKD) (estimated glomerular filtration rate < 60 mL/min/1.73 m2) affects the association has not been investigated. We aim to evaluate this relationship. Methods A retrospective study of consecutive acute ischemic stroke patients was performed. We assessed the risk of severe stroke with the National Institutes of Health Stroke Scale (NIHSS) ≥ 5 at admission and poor outcome with the modified Rankin Scale (mRS) ≥ 3 at discharge. Multivariate stepwise logistic regression models were adopted to study interaction and independent association of lipid components with stroke severity and outcome according to lipid level quartiles by CKD stratification. Results Among the 875 included patients (mean age 64.9 years, 67.8% males), 213 (24.3%) presented with CKD. Elevated low-density lipoprotein cholesterol (LDL-C) was independently associated with severe stroke in patients with CKD (P for trend = 0.033) than in those without CKD (P for trend = 0.121). The association between the level of LDL-C and stroke severity was appreciably modified by CKD (Pinteraction = 0.013). Compared with without CKD patients in the lowest LDL-C quartile, the multivariable-adjusted risk of severe stroke increased significantly by 2.9-fold (95% CI 1.48–5.74) in patients with CKD in the highest LDL-C quartile. No significant association was observed between lipid components and early outcome in patients with and without CKD. Conclusion LDL-C levels are positively associated with stroke severity in only patients with CKD, with an interactive impact of LDL-C and CKD on ischemic stroke in the acute phase.

scholarly journals Radiation outcome in mechanical thrombectomy of acute ischemic stroke

2019 ◽  
Vol 10 (1) ◽  
pp. 10-13 ◽  
Author(s):  
Xiaoying Cai ◽  
Xianhui Ding ◽  
Wenbin Wang ◽  
Ke Yang ◽  
Zhiming Zhou ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Cerebral Artery ◽  
Mechanical Thrombectomy ◽  
Skin Diseases ◽  
Artery Occlusion ◽  
Stroke Severity ◽  
Large Artery ◽  
Operation Duration ◽  
Cerebral Artery Occlusion

Abstract Objective Mechanical thrombectomy is recommended for acute ischemic stroke (AIS) with large artery occlusion. Radiation during the endovascular procedure would increase the risk of skin diseases. We sought to identify radiation outcomes during mechanical thrombectomy. Methodology We prospectively collected and analyzed radiation parameters during mechanical thrombectomy in 41 patients affected with acute cerebral artery occlusion. Results There were 41 cases (68.73 ± 11.05 years) in this study, with a National Institute Health Stroke Scale (NIHSS) score of 15.66 ± 5.94. The time parameters were recorded as following: 84.45 ± 31.66 min (operation duration), 129.71 ± 81.14 s (angiographic run), 16.02 ± 11.03 min (fluoroscopy) and 18.19 ± 11.14 min (angiographic exposure). The doses produced in the procedure were: 1276.43 ± 1647.56 mGy (shot dose), 607.26 ± 412.34 mGy (fluoroscopy) and 1635.52 ± 593.65 mGy (angiographic exposure). Further analysis discovered no association between NIHSS and these time and radiation parameters (P > 0.05). Conclusion This study provided the description of radiation details during mechanical thrombectomy for acute cerebral artery occlusion. The stroke severity would not influence the procedure parameters.

Stentul JJ ureteral - care este optiunea mai buna? New Considerations Regarding Chronic Kidney Disease, Cardiovascular Disease and Dyslipidemia in Diabetic Patients

2018 ◽  
Vol 69 (8) ◽  
pp. 2064-2066
Author(s):  
Mircea Munteanu ◽  
Adrian Apostol ◽  
Viviana Ivan
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Total Cholesterol ◽  
Total Cholesterol Level ◽  
Vascular Complications ◽  
Hdl Cholesterol ◽  
Controlled Study ◽  
Diabetic Patients ◽  
Artery Disease

The aim of the present study is to investigate the prevalance of chronic kidney disease (CKD), of cardiovascular disease (CVD) and dyslipidemia in patients with diabetes mellitus (DM). We conducted a prospective, controlled study involving 420 diabetic patients (120 T1DM, 300 T2DM) and investigate the following aspects: the presence of vascular complications (stroke, coronary artery disease, peripheral artery disease), lipid profile (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), kidney function (glomerular filtration rate, albuminuria), blood pressure, HbA1C. The results that in diabetic patients with CKD there is an increased prevalence of CVD and of dislipidemia. Also we noticed a negative correlation between total cholesterol level and decease in eGFR in all patients, with or without CKD.

Energy-Sensing Pathways in Ischemia: The Counterbalance Between AMPK and mTORC

2020 ◽  
Vol 25 (45) ◽  
pp. 4763-4770
Author(s):  
Angel Cespedes ◽  
Mario Villa ◽  
Irene Benito-Cuesta ◽  
Maria J. Perez-Alvarez ◽  
Lara Ordoñez ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Cause Of Death ◽  
Artery Occlusion ◽  
Brain Pathology ◽  
Common Cause ◽  
Specific Analysis ◽  
Energy Sensing ◽  
Cerebral Artery Occlusion

: Stroke is an important cause of death and disability, and it is the second leading cause of death worldwide. In humans, middle cerebral artery occlusion (MCAO) is the most common cause of ischemic stroke. The damage occurs due to the lack of nutrients and oxygen contributed by the blood flow. : The present review aims to analyze to what extent the lack of each of the elements of the system leads to damage and which mechanisms are unaffected by this deficiency. We believe that the specific analysis of the effect of lack of each component could lead to the emergence of new therapeutic targets for this important brain pathology.

Cerebrolysin and Aquaporin 4 Inhibition Improve Pathological and Motor Recovery after Ischemic Stroke

2018 ◽  
Vol 17 (4) ◽  
pp. 299-308 ◽  
Author(s):  
Bogdan Catalin ◽  
Otilia-Constantina Rogoveanu ◽  
Ionica Pirici ◽  
Tudor Adrian Balseanu ◽  
Adina Stan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Vasogenic Edema ◽  
Artery Occlusion ◽  
Aquaporin 4 ◽  
Hypertonic Solution ◽  
Water Metabolism ◽  
Scar Region ◽  
Function Preservation ◽  
Neurotropic Factor ◽  
Cerebral Artery Occlusion

Background: Edema represents one of the earliest negative markers of survival and consecutive neurological deficit following stroke. The mixture of cellular and vasogenic edema makes treating this condition complicated, and to date, there is no pathogenically oriented drug treatment for edema, which leaves parenteral administration of a hypertonic solution as the only non-surgical alternative. Objective: New insights into water metabolism in the brain have opened the way for molecular targeted treatment, with aquaporin 4 channels (AQP4) taking center stage. We aimed here to assess the effect of inhibiting AQP4 together with the administration of a neurotropic factor (Cerebrolysin) in ischemic stroke. Methods: Using a permanent medial cerebral artery occlusion rat model, we administrated a single dose of the AQP4 inhibitor TGN-020 (100 mg/kg) at 15 minutes after ischemia followed by daily Cerebrolysin dosing (5ml/kg) for seven days. Rotarod motor testing and neuropathology examinations were next performed. Results: We showed first that the combination treatment animals have a better motor function preservation at seven days after permanent ischemia. We have also identified distinct cellular contributions that represent the bases of behavior testing, such as less astrocyte scarring and a larger neuronalsurvival phenotype rate in animals treated with both compounds than in animals treated with Cerebrolysin alone or untreated animals. Conclusion: Our data show that water diffusion inhibition and Cerebrolysin administration after focal ischemic stroke reduces infarct size, leading to a higher neuronal survival in the peri-core glial scar region.

scholarly journals Guidelines adherence in the prevention and management of chronic kidney disease in patients with diabetes mellitus on the background of recent European recommendations – a registry-based analysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Peter Bramlage ◽  
Stefanie Lanzinger ◽  
Sascha R. Tittel ◽  
Eva Hess ◽  
Simon Fahrner ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Clinical Practice ◽  
Kidney Disease ◽  
Analysis Data ◽  
Disease Diagnosis ◽  
Diabetic Patients ◽  
European Society Of Cardiology

Abstract Background Recent European Society of Cardiology (ESC)/European Association for the Study of Diabetes (EASD) guidelines provide recommendations for detecting and treating chronic kidney disease (CKD) in diabetic patients. We compared clinical practice with guidelines to determine areas for improvement. Methods German database analysis of 675,628 patients with type 1 or type 2 diabetes, with 134,395 included in this analysis. Data were compared with ESC/EASD recommendations. Results This analysis included 17,649 and 116,747 patients with type 1 and type 2 diabetes, respectively. The analysis showed that 44.1 and 49.1 % patients with type 1 and type 2 diabetes, respectively, were annually screened for CKD. Despite anti-diabetic treatment, only 27.2 % patients with type 1 and 43.5 % patients with type 2 achieved a target HbA1c of < 7.0 %. Use of sodium-glucose transport protein 2 inhibitors (1.5 % type 1/8.7 % type 2 diabetes) and glucagon-like peptide-1 receptor agonists (0.6 % type 1/5.2 % type 2 diabetes) was limited. Hypertension was controlled according to guidelines in 41.1 and 67.7 % patients aged 18–65 years with type 1 and 2 diabetes, respectively, (62.4 vs. 68.4 % in patients > 65 years). Renin angiotensin aldosterone inhibitors were used in 24.0 and 40.9 % patients with type 1 diabetes (micro- vs. macroalbuminuria) and 39.9 and 47.7 %, respectively, in type 2 diabetes. Conclusions Data indicate there is room for improvement in caring for diabetic patients with respect to renal disease diagnosis and treatment. While specific and potentially clinically justified reasons for non-compliance exist, the data may serve well for a critical appraisal of clinical practice decisions.

scholarly journals The Key Regulator of Necroptosis, RIP1 Kinase, Contributes to the Formation of Astrogliosis and Glial Scar in Ischemic Stroke

2021 ◽  
Author(s):  
Yong-Ming Zhu ◽  
Liang Lin ◽  
Chao Wei ◽  
Yi Guo ◽  
Yuan Qin ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Glial Scar ◽  
Scar Formation ◽  
Reactive Astrocytes ◽  
Interacting Protein ◽  
Protein Levels ◽  
Endothelial Growth Factor ◽  
Cerebral Artery Occlusion

AbstractNecroptosis initiation relies on the receptor-interacting protein 1 kinase (RIP1K). We recently reported that genetic and pharmacological inhibition of RIP1K produces protection against ischemic stroke-induced astrocytic injury. However, the role of RIP1K in ischemic stroke-induced formation of astrogliosis and glial scar remains unknown. Here, in a transient middle cerebral artery occlusion (tMCAO) rat model and an oxygen and glucose deprivation and reoxygenation (OGD/Re)-induced astrocytic injury model, we show that RIP1K was significantly elevated in the reactive astrocytes. Knockdown of RIP1K or delayed administration of RIP1K inhibitor Nec-1 down-regulated the glial scar markers, improved ischemic stroke-induced necrotic morphology and neurologic deficits, and reduced the volume of brain atrophy. Moreover, knockdown of RIP1K attenuated astrocytic cell death and proliferation and promoted neuronal axonal generation in a neuron and astrocyte co-culture system. Both vascular endothelial growth factor D (VEGF-D) and its receptor VEGFR-3 were elevated in the reactive astrocytes; simultaneously, VEGF-D was increased in the medium of astrocytes exposed to OGD/Re. Knockdown of RIP1K down-regulated VEGF-D gene and protein levels in the reactive astrocytes. Treatment with 400 ng/ml recombinant VEGF-D induced the formation of glial scar; conversely, the inhibitor of VEGFR-3 suppressed OGD/Re-induced glial scar formation. RIP3K and MLKL may be involved in glial scar formation. Taken together, these results suggest that RIP1K participates in the formation of astrogliosis and glial scar via impairment of normal astrocyte responses and enhancing the astrocytic VEGF-D/VEGFR-3 signaling pathways. Inhibition of RIP1K promotes the brain functional recovery partially via suppressing the formation of astrogliosis and glial scar. Graphical Abstract

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