Abstract WP161: Sovateltide Promotes Regeneration and Functional Recovery of Ischemic Brain by Improving Mitochondrial Function

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Amaresh Ranjan ◽  
Thomas Hauert ◽  
Mazin Hussain ◽  
Anthony Giometti ◽  
Seema Briyal ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Vehicle Group ◽  
Mitochondrial Activity ◽  
Mitochondrial Morphology ◽  
Specific Gene ◽  
Tem Analysis ◽  
Cross Sectional ◽  
Brain Functions ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

Mitochondrial dysfunction is associated with cerebral ischemic stroke. Sovateltide (IRL-1620; PMZ-1620) undergoing clinical trials (NCT04047563; NCT04046484) has been demonstrated, in preclinical studies, to provide recovery of brain functions when administered following acute cerebral ischemic stroke. We hypothesize that sovateltide preserves mitochondrial activity and provides neural protection and regeneration. We investigated the effect of sovateltide on mitochondrial morphology and function following acute cerebral ischemic stroke. Rats underwent permanent middle cerebral artery occlusion (MCAO) and then received three intravenous injections of vehicle or sovateltide (5 μg/kg) at 4, 6, and 8 h and sacrificed at 24 h post MCAO. Another set of rats were treated similarly on day 0, 3 and 6 and sacrificed on day 7. Western blot and/or immunofluorescence were used to evaluate protein expression of NeuroD1, DoubleCortin, HUC+HUD, NeuN, Sox2, Oct4, DRP1 and MFN2. Mitochondrial biogenesis was evaluated using in situ PCR and transmission electron microscopy (TEM). Sovateltide produced (p<0.001) improvement in neurological deficit and motor function compared to vehicle at 24 h and day 7 post MCAO. Expression of NeuroD1 (p=0.0003), HuC-HuD (p=0.0373) and DoubleCortin (p=0.013) was higher in sovateltide compared to vehicle at 24 h but not at day 7. No change in Oct4 and Sox2 was observed. Immunofluorescence of cultured NPCs showed elevated expression of NeuroD1 and NeuN in sovateltide compared to vehicle. Sovateltide significantly decreased fission marker, DRP1 (p<0.001) and increased fusion marker MFN2 (p<0.0001) at 24 h and day 7 compared to vehicle. A significantly increased mitochondrial DNA (MT-ATP8, mitochondria specific gene) fluorescence in sovateltide group compared to vehicle (p=0.0418) and sham (p=0.0085) was observed. TEM analysis showed significant increase in mitochondrial cross-sectional area x number and % mitochondrial/tissue area in sovateltide group at 24 hours compared to vehicle. Mitochondrial number increased (p=0.032) at day 7 compared to 24 h in vehicle group. Sovateltide preserves mitochondrial activity and provides neural protection and regeneration in rat model of acute cerebral ischemic stroke.

scholarly journals Influence of the Volume of the Ischemic Origin on Clinical Outcomes of the Brain Stroke

2019 ◽  
pp. 1-3
Author(s):  
Z. A. Akbarkhodjaeva ◽  
G. S. Rakhimbaeva
Keyword(s):  
Ischemic Stroke ◽  
Clinical Outcomes ◽  
Brain Diseases ◽  
Brain Functions ◽  
Large Size ◽  
Brain Stroke ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic ◽  
Relationship Of ◽  
The Brain

In this article authors discussed about the influence of volume of the ischemic origin on clinical outcomes in patients with stroke. Cerebral ischemic stroke is one of the main cause of death among cardiovascular and brain diseases. The study is dedicated to learn the relationship of the dynamics of the volume of the ischemic focus with clinical outcome of stroke. For this study, 125 patients were examined and analyzed. MRI of the brain in acute period of ischemic stroke in 78% of patients were assessed that foci of ischemia of small (less than 10 cm3), medium (10-50 cm3) and large size (more than 50 cm3). Lacunarstrokes, as well as the size of the penumbra, affecting the ability to restore impaired brain functions, can be identified only by magnetic resonance imaging of the brain.

Irisin Ameliorates Hypoxia/Reoxygenation-Induced Inflammation and Apoptosis in PC12 Cells by Inhibiting TLR4/MYD88 Signaling Pathway

2019 ◽  
Vol 17 (3) ◽  
pp. 329-336
Author(s):  
Wang Jinli ◽  
Xu Fenfen ◽  
Zheng Yuan ◽  
Cheng Xu ◽  
Zhang Piaopiao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Major Complication ◽  
Lactic Dehydrogenase ◽  
Dependent Manner ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic ◽  
Myd88 Signaling ◽  
Hypoxia Reoxygenation

Cardiovascular disease including cerebral ischemic stroke is the major complication that increases the morbidity and mortality in patients with diabetes mellitus as much as four times. It has been well established that irisin, with its ability to regulate glucose and lipid homeostasis as well as anti-inflammatory and anti-apoptotic properties, has been widely examined for its therapeutic potentials in managing metabolic disorders. However, the mechanism of irisin in the regulation of cerebral ischemic stroke remains unclear. Using PC12 cells as a model, we have shown that hypoxia/reoxygenation inhibits cell viability and increases lactic dehydrogenase. Irisin, in a dose-dependent manner, reversed these changes. The increase in inflammatory mediators (IL-1β, IL-6, and TNF-α) by hypoxia/reoxygenation was reversed by irisin. Furthermore, the cell apoptosis promoted by hypoxia/reoxygenation was also inhibited by irisin. Irisin suppressed TLR4/MyD88 signaling pathway leading to amelioration of inflammation and apoptosis in PC12 cells. Thus, inhibition of TLR4/MyD88 signaling pathway via irisin could be an important mechanism in the regulation of hypoxia/reoxygenation-induced inflammation and apoptosis in PC12 cells.

T Cells and Cerebral Ischemic Stroke

2015 ◽  
Vol 40 (9) ◽  
pp. 1786-1791 ◽  
Author(s):  
Lijuan Gu ◽  
Zhihong Jian ◽  
Creed Stary ◽  
Xiaoxing Xiong
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

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

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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