scholarly journals Galectin-3 protects against ischemic stroke by promoting neuro-angiogenesis via apoptosis inhibition and Akt/Caspase regulation

2020 ◽  
pp. 0271678X2093113
Author(s):  
Umadevi V Wesley ◽  
Ian C Sutton ◽  
Katelin Cunningham ◽  
Jacob W Jaeger ◽  
Allan Q Phan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Rat Brain ◽  
Functional Recovery ◽  
Neuronal Cell ◽  
Vessel Density ◽  
Angiogenic Factor ◽  
Ischemic Lesion ◽  
Post Stroke ◽  
Phosphorylated Akt ◽  
Galectin 3

Post-stroke neurological deficits and mortality are often associated with vascular disruption and neuronal apoptosis. Galectin-3 (Gal3) is a potent pro-survival and angiogenic factor. However, little is known about its protective role in the cerebral ischemia/reperfusion (I/R) injury. We have previously shown significant up-regulation of Gal3 in the post-stroke rat brain, and that blocking of Gal3 with neutralizing antibody decreases the cerebral blood vessel density. Our current study demonstrates that intracerebral local delivery of the Gal3 into rat brain at the time of reperfusion exerts neuroprotection. Ischemic lesion volume and neuronal cell death were significantly reduced as compared with the vehicle-treated MCAO rat brains. Gal3 increased vessel density and neuronal survival after I/R in rat brains. Importantly, Gal3-treated groups showed significant improvement in motor and sensory functional recovery. Gal3 increased neuronal cell viability under in vitro oxygen–glucose deprivation conditions in association with increased phosphorylated-Akt, decreased phosphorylated-ERK1/2, and reduced caspase-3 activity. Gene expression analysis showed down regulation of pro-apoptotic and inflammatory genes including Fas-ligand, and upregulation of pro-survival and pro-angiogenic genes including Bcl-2, PECAM, and occludin. These results indicate a key role for Gal3 in neuro-vascular protection and functional recovery following ischemic stroke through modulation of angiogenic and apoptotic pathways.

scholarly journals Protection against Neurological Symptoms by Consuming Corn Silk Water Extract in Artery-Occluded Gerbils with Reducing Oxidative Stress, Inflammation, and Post-Stroke Hyperglycemia through the Gut-Brain Axis

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 168
Author(s):  
Jin Ah Ryuk ◽  
Byoung Seob Ko ◽  
Na Rang Moon ◽  
Sunmin Park
Keyword(s):  
Ischemic Stroke ◽  
Neuronal Cell Death ◽  
Cell Mass ◽  
Water Extract ◽  
Neuronal Cell ◽  
Artery Occlusion ◽  
Sham Control ◽  
Β Cell ◽  
Post Stroke ◽  
Corn Silk

Corn silk (Stigma maydis), rich in flavonoids, is traditionally used to treat edema, depression, and hyperglycemia and may alleviate ischemic stroke symptoms in Chinese medicine. This study examined whether corn silk water extract (CSW) could alleviate ischemic stroke symptoms and post-stroke hyperglycemia in Mongolian gerbils with transient cerebral ischemia and reperfusion (I/R). After being given 0.05% (I/R-LCSW) and 0.2% (I/R-HCSW), 0.02% aspirin (I/R-aspirin), and cellulose (I/R-control) in their 40 energy% fat diets for three weeks, the gerbils underwent an artery occlusion for eight minutes and reperfusion. They took the assigned diet for an additional three weeks. Sham-operated gerbils without artery occlusion had the same diet as Sham-control. CSW intake reduced neuronal cell death in gerbils with I/R and dose-dependently improved the neurological symptoms, including drooped eyes, crouched posture, flexor reflex, and walking patterns. CSW intake also alleviated the short-term memory and spontaneous alteration and grip strength compared to the I/R-control group. The protection against ischemic stroke symptoms was associated with the reduced tumor necrosis factor-α, interleukin-1β, superoxide, and lipid peroxide levels, promoting superoxide dismutase activity in the hippocampus in the CSW groups, compared to the I/R-control. The blood flow measured by Doppler was improved with CSW compared to the I/R-control. Furthermore, CSW intake prevented the post-stroke hyperglycemia related to decreasing pancreatic β-cell mass as much as the Sham-control, and it was related to protection against β-cell apoptosis, restoring the β-cell mass similar to the Sham-control. CSW intake elevated the relative abundance of Lactobacillus, Bifidobacterium, Allobaculum, and Akkermansia compared to the I/R-control. Picrust2 analysis showed that CSW increased the propionate and butyrate metabolism and the starch and glucose metabolism but reduced lipopolysaccharide biosynthesis compared to the I/R-control. In conclusion, CSW intake protects against neuronal cell death and post-hyperglycemia by reducing oxidative stress and inflammation and increasing blood flow and the β-cell mass. The alleviation was associated with promoting the gut-brain axis by changing the gut microbiome community.

scholarly journals Temporal and Spatial Dynamics of Inflammasome Activation After Ischemic Stroke

2021 ◽  
Vol 12 ◽  
Author(s):  
Danli Lu ◽  
Mengyan Hu ◽  
Bingjun Zhang ◽  
Yinyao Lin ◽  
Qiang Zhu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Spatial Dynamics ◽  
Size Control ◽  
Inflammasome Activation ◽  
Therapeutic Effects ◽  
Ischemic Lesion ◽  
Stroke Outcomes ◽  
Post Stroke ◽  
Caspase 1 ◽  
The Impact

Background: The inflammasome represents a highly pro-inflammatory mechanism. It has been identified that inflammasome was activated after ischemic stroke. However, the impact of inflammasomes on stroke outcomes remains contradictory. The participating molecules and the functioning arena of post-stroke inflammasome activation are still elusive.Methods: In the present study, blood samples from stroke patients were collected and analyzed with flow cytometry to evaluate the correlation of inflammasome activation and stroke outcomes. A stroke model was established using male C57/Bl6 mice with transient middle cerebral artery occlusion (tMCAO, 1 h). The dynamics of inflammasome components, cell type, and location of inflammasome activation and the therapeutic effects of inhibiting post-stroke inflammasome executors were evaluated.Results: We found that a high level of inflammasome activation might indicate detrimental stroke outcomes in patients and mice models. Post-stroke inflammasome activation, especially NLRP3, cleaved Caspase-1, cleaved Caspase-11, IL-1β, IL-18, and GSDMD, peaked at 3–5 days and declined at 7 days with the participation of multiple components in mice. Macrophage that infiltrated into the ischemic lesion was the main arena for post-stroke inflammasome activation among myeloid cells according to the data of mice. Among all the members of the Caspase family, Caspase-1 and −11 served as the main executing enzymes. Inhibiting Caspase-1/−11 signaling efficiently suppressed DAMPs-induced macrophage inflammasome activation and displayed neuroprotection to stroke models including infarct size (Control: 48.05 ± 14.98; Cas1.i: 19.34 ± 12.21; Cas11.i: 21.43 ± 14.67, P < 0.001) and neurological deficit score (0 d-Control: 2.20 ± 0.63; 0 d-Cas1.i: 2.20 ± 0.63; 0 d-Cas11.i: 2.20 ± 0.63; 1 d-Control: 2.50 ± 0.53; 1 d-Cas1.i: 1.50 ± 0.71; 1 d-Cas11.i: 2.00 ± 0.67; 2 d-Control: 2.30 ± 0.48; 2 d-Cas1.i: 1.30 ± 0.48; 2 d-Cas11.i: 1.50 ± 0.53; 3 d-Control: 2.00 ± 0.67; 3 d-Cas1.i: 1.20 ± 0.42; 3 d-Cas11.i: 1.30 ± 0.48, P < 0.001).Conclusions: Taken together, inflammasome activation played a detrimental role in stroke pathology. Targeting post-stroke inflammasome executing enzymes fitting in the dynamics of macrophages might obtain potential and efficient therapeutic effects.

scholarly journals ЗАСТОСУВАННЯ Α-ГЛІЦЕРИЛФОСФОРИЛХОЛІНУ В СХЕМІ КОМПЛЕКСНОГО ЛІКУВАННЯ ДЛЯ ФУНКЦІОНАЛЬНОГО ВІДНОВЛЕННЯ ПІСЛЯ МОЗКОВОГО ПІВКУЛЬОВОГО ІШЕМІЧНОГО ІНСУЛЬТУ

2021 ◽  
Vol 25 (3-4) ◽  
pp. 8-13
Author(s):  
О.О. Пушко ◽  
Н.В. Литвиненко
Keyword(s):  
Ischemic Stroke ◽  
Functional Recovery ◽  
Vascular Diseases ◽  
Comprehensive Treatment ◽  
Post Stroke ◽  
Rehabilitation Programs ◽  
Comprehensive Therapy ◽  
Progressive Growth ◽  
Active Rehabilitation ◽  
Combination Of Methods

The article considers the influence of α-glycerylphosphorylcholine in the scheme of comprehensive therapy on the dynamics of functional recovery in patients with cerebral hemispheric ischemic stroke. Against the background of the progressive growth of acute cerebral infarction, the problem of timely care is relevant. Timely treatment of stroke, based on evidence-based medicine, along with early activation and rehabilitation of patients is designed to reduce mortality and subsequent disability of patients. Given that cholinergic insufficiency and structural and functional damage of neurons play an important role in the pathogenesis of post-stroke disorders, the use of medicines for their correction, in particular α-glycerylphosphorylcholine, is justified. Choline alfoscerate, a precursor of acetylcholine and phosphatidylcholine, is broken down by enzymes into choline and glycerophosphate when ingested, and the choline thus obtained is able to improve neuronal functionality in patients with neurodegenerative and vascular diseases. The study revealed a significantly better recovery of impaired motor and cognitive functions after cerebral hemispheric stroke under the influence of comprehensive therapeutic and rehabilitation measures using active rehabilitation methods in conjunction with α-glycerylphosphorylcholine. The results obtained during the study allow us to report the advantage of a combination of methods of active rehabilitation and the use of the pharmacological agent α-glycerylphosphorylcholine. The feasibility and efficacy of α-glycerylphosphorylcholine are related to its ability to reduce motor and cognitive deficits after ischemic stroke. The scheme of comprehensive treatment of patients in acute and restorative periods of cerebral hemispheric ischemic stroke with the use of α-glycerylphosphorylcholine helps to increase the effectiveness of functional recovery after an acute cerebral accident, and can be used in the use of therapeutic and rehabilitation programs for patients after cerebral hemispheric ischemic stroke to reduce the post-stroke deficit.

scholarly journals GAT3 selective substrate l-isoserine upregulates GAT3 expression and increases functional recovery after a focal ischemic stroke in mice

2017 ◽  
Vol 39 (1) ◽  
pp. 74-88 ◽  
Author(s):  
Maria EK Lie ◽  
Emma K Gowing ◽  
Nina B Johansen ◽  
Nils Ole Dalby ◽  
Louise Thiesen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Recovery ◽  
Surface Expression ◽  
Tonic Inhibition ◽  
Stroke Recovery ◽  
Gaba Uptake ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Post Stroke ◽  
Long Term Treatment

Ischemic stroke triggers an elevation in tonic GABA inhibition that impairs the ability of the brain to form new structural and functional cortical circuits required for recovery. This stroke-induced increase in tonic inhibition is caused by impaired GABA uptake via the glial GABA transporter GAT3, highlighting GAT3 as a novel target in stroke recovery. Using a photothrombotic stroke mouse model, we show that GAT3 protein levels are decreased in peri-infarct tissue from 6 h to 42 days post-stroke. Prior studies have shown that GAT substrates can increase GAT surface expression. Therefore, we aimed to assess whether the GAT3 substrate, L-isoserine, could increase post-stroke functional recovery. L-Isoserine (38 µM or 380 µM) administered directly into the infarct from day 5 to 32 post-stroke, significantly increased motor performance in the grid-walking and cylinder tasks in a concentration-dependent manner, without affecting infarct volumes. Additionally, L-isoserine induced a lasting increase in GAT3 expression in peri-infarct regions accompanied by a small decrease in GFAP expression. This study is the first to show that a GAT3 substrate can increase GAT3 expression and functional recovery after focal ischemic stroke following a delayed long-term treatment. We propose that enhancing GAT3-mediated uptake dampens tonic inhibition and promotes functional recovery after stroke.

scholarly journals Post-stroke Delivery of Valproic acid Promotes Functional Recovery and Differentially Modifies Responses of Peri-infarct Microglia

2020 ◽  
Author(s):  
Tung-Tai Kuo ◽  
Yuan-Hao Chen ◽  
Vicki Wang ◽  
Jui-Sheng Wu ◽  
Kuan-Yin Tseng
Keyword(s):  
Extracellular Matrix ◽  
Valproic Acid ◽  
Functional Recovery ◽  
Microglial Activation ◽  
Low Dose ◽  
Infarct Volume ◽  
Post Stroke ◽  
Qpcr Analysis ◽  
Circularity Index ◽  
Galectin 3

Abstract Background: Recently, microglia, being the determinant of environment in peri-infarct tissue and strongly influence the potential for neuronal plasticity, has been implicated in post-ischemic secondary injury and functional recovery. However, the specific role of peri-infarct microglia and the timing of its morphological changes following ischemic stroke are not well understood. Valproic acid (VPA) can protect against ischemic damage and promote recovery. These effects are usually attributed, at least partially, to the anti-inflammatory ability of this drug to suppress microglial activation. In this study, we explored whether a low dose of VPA after stroke could modify reactive responses in microglia/macrophages and optimize peri-infarct microenvironments to improve functional recovery.Methods: Male Sprague-Dawley rats were subjected to distal middle cerebral artery occlusion (dMCAo) for 90 minutes, followed by reperfusion. Some received a single injection of VPA (200 mg/kg) 90 minutes after the induction of ischemia, while vehicle-treated animals underwent the same procedure with physiological saline. Infarction volume was calculated at 48 hours after reperfusion, and neurological symptoms were evaluated through 48 hours thereafter. The production of cytokines and biomarkers after insult was determined using enzyme-linked immunosorbent assays (ELISAs) and western blot. The effects of VPA on the activation of peri-infarct CD11b-positive cells were assessed based on cellular density and quality observation of morphology with fractal analysis and circularity index. The expressions of genes within peri-infarct zones at 3 days were determined by RNA-sequencing analysis. To determine whether VPA modulates microglial polarization, gentleMACS Dissociator was used to isolate CD11b-positive cells from the peri-infarct cortex of rats treated with or without VPA 3 days after dMCAo, after which the cells were subjected to qPCR analysis.Results: 200 mg/kg of VPA injected 90 minutes after ischemia induction did not significantly reduce infarct volume but did improve neurological deficit at least partially compared with vehicle. Meanwhile, VPA significantly reduced dMCAo-induced elevation of IL-6 at 24 hours post-stroke and significantly decreased the number of CD11b-positive microglia/macrophages within peri-infarct cortex at 7 but not at 2 days. Morphological analysis revealed that VPA therapy leads to higher fractal dimensions and lower circularity index of CD11b-positive cells within peri-infarct cortex at both 2 days and 7 days, suggesting that VPA has core effects on microglial activation. The attenuation of microglia/macrophage activation caused by VPA might involve HDAC inhibition-mediated suppression of galectin-3 production. Analysis of VPA-induced changes to gene expressions in the peri-infarct cortex at 3 days post-stroke indicated the upregulation of wound healing, collagen trimmer, and extracellular matrix genes. Furthermore, qPCR analysis of CD11b-positive cells suggested that VPA could partially enhance M2 subset polarization of microglia/macrophages in peri-infarct cortex.Conclusions: Our results are the first to show that a low dose of VPA promotes short-term functional recovery but does not alter infarct volume. The decreases in the expression of both IL-6 and galectin-3 might influence the extracellular matrix remodeling and morphological characteristics and transcriptional profiles of microglia/macrophages, which could contribute to the improved recovery.

Abstract TMP121: Gender Differences in Functional Outcomes After Acute Ischemic Stroke: The Role of White Matter Structural Integrity

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Mark Etherton ◽  
Ona Wu ◽  
Pedro Cougo ◽  
Anne-Katrin Giese ◽  
Lisa Cloonan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Functional Recovery ◽  
Stroke Subtype ◽  
Post Stroke ◽  
Significant Difference ◽  
Acute Infarct ◽  
Underlying Mechanisms ◽  
Microstructural Integrity

Background: Women are known to have worse post-stroke outcomes; however, the underlying mechanisms remain unclear. We evaluated sex-specific clinical and neuroimaging characteristics linked to cerebrovascular brain health in association with functional recovery after acute ischemic stroke (AIS). Methods: We reviewed 316 AIS patients with acute MRI (<48 hours from symptom onset) and modified Rankin scale score (mRS) assessed at 3-6 months post-stroke. Acute infarct volume on diffusion-weighted imaging (DWIv) and white matter hyperintensity volume (WMHv) on FLAIR sequences were determined using a validated semi-automated method. Mean diffusivity (MD) and fractional anisotropy (FA) of normal appearing white matter (NAWM) were derived from the contralesional hemisphere. Wilcoxon rank sum, Spearman correlation, and Fisher’s exact tests were used at p-value <0.05, as appropriate. Results: Women comprised 41.1% of this AIS cohort, and as compared to men, they were older (68 vs. 62.8 years, p = 0.002), had higher prevalence of atrial fibrillation (21.5% vs. 12.4%, p = 0.04), and less tobacco use (21.1% vs. 36.3%, p = 0.03). There was no statistically significant difference between men and women in admission stroke severity, TOAST stroke subtype distribution, DWIv or WMHv. However, women were significantly less likely to have a favorable outcome (mRS <2), as compared to men (53.7% vs. 68.5%, p = 0.01). Both FA (ρ -0.18, p=0.04) and MD (ρ 0.28, p=0.002) values in NAWM correlated with follow-up mRS in women, but only MD (ρ 0.26, p=0.0004) in men. Conclusion: Despite no differences in admission NIHSS, acute infarct size, WMH burden or stroke subtype, women with AIS had significantly worse post-stroke outcomes in our cohort. Our findings suggest that microstructural integrity, as assessed by NAWM diffusivity anisotropy measurements, may represent a neuroimaging correlate of worse outcomes in women. The correlation between markers of white matter microstructural integrity and long-term mRS provides insight into the underlying mechanisms of disease that may influence functional recovery after stroke.

scholarly journals Assessment of Post-Stroke Consequences in Pediatric Ischemic Stroke in the Context of Neuroimaging Results—Experience from a Single Medical Center

Children ◽  
2021 ◽  
Vol 8 (4) ◽  
pp. 292
Author(s):  
Ilona Kopyta ◽  
Beata Sarecka-Hujar ◽  
Dorota Raczkiewicz ◽  
Katarzyna Gruszczyńska ◽  
Magdalena Machnikowska-Sokołowska
Keyword(s):  
Ischemic Stroke ◽  
Medical Center ◽  
Vascular Pathology ◽  
Arterial Ischemic Stroke ◽  
Stroke Subtype ◽  
Ischemic Lesion ◽  
Early Therapy ◽  
Stroke Outcomes ◽  
Post Stroke ◽  
Tertiary Center

Arterial ischemic stroke (AIS) in children is a rare condition; its frequency is estimated at 0.58 to 7.9 new onsets in 100,000 children per year. The knowledge on risk factors, clinical outcomes and consequences of pediatric AIS is increasing. However, there are still many unknowns in the field. The aim of the study was to analyze the clinical presentation of pediatric AIS and its consequences according to the neuroimaging results and location of ischemia. The research was retrospective and observational. The analyzed group consisted of 75 AIS children (32 girls, 43 boys), whereby the age of the patients ranged from 9 months to 18 years at stroke onset. All the patients were diagnosed and treated in one tertiary center. The most frequent stroke subtype was total anterior circulation infarct (TACI) with most common ischemic focus location in temporal lobe and vascular pathology in middle cerebral artery (MCA). The location of ischemic focus in the brain correlated with post-stroke outcomes: intellectual delay and epilepsy, hemiparesis corresponded to the location of vascular pathology. A correlation found between ischemic lesion location and vascular pathology with post-stroke consequences in pediatric AIS may be important information and helpful in choosing proper early therapy. The expected results should lead to lesser severity of late post-stroke outcomes.

scholarly journals Transplantation of bFGF-expressing neural stem cells promotes cell migration and functional recovery in rat brain after transient ischemic stroke

Oncotarget ◽  
2017 ◽  
Vol 8 (60) ◽  
pp. 102067-102077 ◽  
Author(s):  
Jin-Jing Zhang ◽  
Juan-Juan Zhu ◽  
Yuan-Bo Hu ◽  
Guang-Heng Xiang ◽  
Lian-Cheng Deng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Migration ◽  
Ischemic Stroke ◽  
Neural Stem Cells ◽  
Rat Brain ◽  
Functional Recovery

scholarly journals Ambroxol Upregulates Glucocerebrosidase Expression to Promote Neural Stem Cells Differentiation Into Neurons Through Wnt/β-Catenin Pathway After Ischemic Stroke

2021 ◽  
Vol 13 ◽  
Author(s):  
Hongfei Ge ◽  
Chao Zhang ◽  
Yang Yang ◽  
Weixiang Chen ◽  
Jun Zhong ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Recovery ◽  
Infarct Volume ◽  
Basic Knowledge ◽  
Brain Disorders ◽  
Potential Mechanism ◽  
Stroke Patients ◽  
Stroke Treatment ◽  
Post Stroke

Ischemic stroke has been becoming one of the leading causes resulting in mortality and adult long-term disability worldwide. Post-stroke pneumonia is a common complication in patients with ischemic stroke and always associated with 1-year mortality. Though ambroxol therapy often serves as a supplementary treatment for post-stroke pneumonia in ischemic stroke patients, its effect on functional recovery and potential mechanism after ischemic stroke remain elusive. In the present study, the results indicated that administration of 70 mg/kg and 100 mg/kg enhanced functional recovery by virtue of decreasing infarct volume. The potential mechanism, to some extent, was due to promoting NSCs differentiation into neurons and interfering NSCs differentiation into astrocytes through increasing GCase expression to activate Wnt/β-catenin signaling pathway in penumbra after ischemic stroke, which advanced basic knowledge of ambroxol in regulating NSCs differentiation and provided a feasible therapy for ischemic stroke treatment, even in other brain disorders in clinic.

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