scholarly journals Intravenous Administration of Coenzyme Q10 in Acute Period of Cerebral Ischemia Decreases Mortality by Reducing Brain Necrosis and Limiting Its Increase within 4 Days in Rat Stroke Model

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1240
Author(s):  
Obolenskaia Olga Nikolaevna ◽  
Gorodetskaya Evgeniya Aronovna ◽  
Kalenikova Elena Igorevna ◽  
Belousova Margarita Alekseevna ◽  
Gulyaev Mikhail Vladimirovich ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Intravenous Administration ◽  
Coenzyme Q10 ◽  
Brain Lesion ◽  
Neurological Status ◽  
Brain Necrosis ◽  
Rate Improvement ◽  
The Brain ◽  
Targeting Effect

Oxidative stress plays a key role in the pathogenesis of ischemic stroke. Coenzyme Q10 has a multi-targeting effect and may protect the brain against ischemic damage. The aim of our study was to evaluate the neuroprotective potential of ubiquinol by its intravenous administration. The study was performed on rats; a stroke was modeled by occlusion of the middle cerebral artery. On days 1 and 4 after ischemia, the neurological deficit and volume of the brain lesion were determined by MRI and TTC staining. Intravenous administration of coenzyme Q10 led to a decrease in rat mortality rate, improvement in neurological status, and decrease in the brain necrosis area in acute and delayed period after cerebral ischemia. A single intravenous administration of ubiquinol led to a limitation of the size of the brain damage for at least four days after ischemia. Thus, intravenous administration of coenzyme Q10 has a persistent neuroprotective potential. This finding suggests a possible therapeutic role of ubiquinol in acute ischemic conditions.

scholarly journals Anti-apoptotic effects of 2-pyrrolidone derivatives in cerebral ischemia

2021 ◽  
Vol 9 (4) ◽  
pp. 517-526
Author(s):  
Dmitriy I. Pozdnyakov ◽  
◽  
Anastasiya V. Sosnovskaya ◽  
Andrey V. Mamleyev ◽  
Alina A. Ladyka ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Caspase 3 ◽  
Reference Drug ◽  
Brain Necrosis ◽  
Wide Range ◽  
Ischemic Period ◽  
Apoptotic Effects ◽  
The Brain ◽  
Ischemic Events ◽  
Neuroprotective Action

INTRODUCTION: Uncontrolled course of apoptosis reactions underlies a wide range of pathological processes, including ischemic events. AIM: To evaluate the anti-apoptotic properties of some racetams in experimental brain ischemia in rats. MATERIALS AND METHODS: Cerebral ischemia was modeled in Wistar rats by irreversible occlusion of the middle cerebral artery. The test-compounds and the reference drug piracetam were administered per os at a dose of 250 mg/kg. After 72 hours of the ischemic period, the activity of apoptotic systems in the brain tissue was evaluated by determining the concentration of the apoptotic-inducing factor (AIF), caspase-3, ionized calcium, the latent opening time of the mitochondrial transition permeability pore and the zone of brain necrosis. RESULTS: The study showed that the use of the studied compounds contributed to a decrease in the intensity of reactions, both caspase-dependent and caspase-independent apoptosis, which was reflected in a decrease in the concentration of AIF and caspase-3 by 32.4% (p < 0.05); 34.6% (p < 0.05); 31.1% (p < 0.05), and 41.9% (p < 0.05); 39.1% (p < 0.05); 34.5% (p < 0.05) when PirPr, PirAc and PirBut were administered, respectively. Also, the use of the studied substances led to an increase in the latent period of opening the mitochondrial transition permeability pore, a decrease in the concentration of intracellular calcium and the zone of brain necrosis. At the same time, the pharmacological effect of the administration of the compound PirAc exceeded the effect of piracetam and other test substances. CONCLUSIONS: Based on the results obtained, it can be assumed that the studied racetams have neuroprotective action, realized through suppression of the reactions of apoptosis.

scholarly journals Histone Deacetylases and Their Isoform-Specific Inhibitors in Ischemic Stroke

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1445
Author(s):  
Svetlana Demyanenko ◽  
Valentina Dzreyan ◽  
Svetlana Sharifulina
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Histone Deacetylases ◽  
Histone Deacetylase Inhibitors ◽  
Neuroprotective Activity ◽  
Stroke Therapy ◽  
Brain Areas ◽  
Histone Deacetylases Inhibitors ◽  
The Brain

Cerebral ischemia is the second leading cause of death in the world and multimodal stroke therapy is needed. The ischemic stroke generally reduces the gene expression due to suppression of acetylation of histones H3 and H4. Histone deacetylases inhibitors have been shown to be effective in protecting the brain from ischemic damage. Histone deacetylases inhibitors induce neurogenesis and angiogenesis in damaged brain areas promoting functional recovery after cerebral ischemia. However, the role of different histone deacetylases isoforms in the survival and death of brain cells after stroke is still controversial. This review aims to analyze the data on the neuroprotective activity of nonspecific and selective histone deacetylase inhibitors in ischemic stroke.

scholarly journals Ischemia-Induced Interleukin-6 as a Potential Endogenous Neuroprotective Cytokine against NMDA Receptor-Mediated Excitoxicity in the Brain

2000 ◽  
Vol 20 (6) ◽  
pp. 956-966 ◽  
Author(s):  
Carine Ali ◽  
Olivier Nicole ◽  
Fabian Docagne ◽  
Sylvain Lesne ◽  
Eric T. MacKenzie ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Nmda Receptor ◽  
Interleukin 6 ◽  
Cortical Neurons ◽  
Focal Cerebral Ischemia ◽  
Calcium Ionophore ◽  
Receptor Activation ◽  
Neuronal Cultures ◽  
The Brain

In the brain, the expression of the pleiotropic cytokine interleukin-6 (IL-6) is enhanced in various chronic or acute central nervous system disorders. However, the significance of IL-6 production in such neuropathologic states remains controversial. The present study investigated the role of IL-6 after cerebral ischemia. First, the authors showed that focal cerebral ischemia in rats early up-regulated the expression of IL-6 mRNA, without affecting the transcription of its receptors (IL-6Rα: and gp130). Similarly, the striatal injection of N-methyl-d-aspartate (NMDA) in rats, a paradigm of excitotoxic injury, activated the expression of IL-6 mRNA. The involvement of glutamatergic receptor activation was further investigated by incubating cortical neurons with NMDA or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA). NMDA and ionomycin (a calcium ionophore) up-regulated IL-6 mRNA, suggesting that neurons may produce IL-6 in response to the calcium influx mediated through NMDA receptors. The potential role of IL-6 during ischemic/excitotoxic insults was then studied by testing the effect of IL-6 against apoptotic or excitotoxic challenges in cortical cultures. IL-6 did not prevent serum deprivation- or staurosporine-induced apoptotic neuronal death, or AMPA/kainate-mediated excitotoxicity. However, in both mixed and pure neuronal cultures, IL-6 dose-dependently protected neurons against NMDA toxicity. This effect was blocked by a competitive inhibitor of IL-6. Overall, the results suggest that the up-regulation of IL-6 induced by cerebral ischemia could represent an endogenous neuroprotective mechanism against NMDA receptor-mediated injury.

scholarly journals Cell Type-Specific Mechanisms in the Pathogenesis of Ischemic Stroke: The Role of Apoptosis Signal-Regulating Kinase 1

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
So Yeong Cheon ◽  
Eun Jung Kim ◽  
Jeong Min Kim ◽  
Bon-Nyeo Koo
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Cerebral Ischemia ◽  
Cell Types ◽  
Ischemic Brain Injury ◽  
Cell Type ◽  
Ischemic Brain ◽  
Cell Type Specific ◽  
The Brain

Stroke has become a more common disease worldwide. Despite great efforts to develop treatment, little is known about ischemic stroke. Cerebral ischemia activates multiple cascades of cell type-specific pathomechanisms. Ischemic brain injury consists of a complex series of cellular reactions in various cell types within the central nervous system (CNS) including platelets, endothelial cells, astrocytes, neutrophils, microglia/macrophages, and neurons. Diverse cellular changes after ischemic injury are likely to induce cell death and tissue damage in the brain. Since cells in the brain exhibit different functional roles at distinct time points after injury (acute/subacute/chronic phases), it is difficult to pinpoint genuine roles of cell types after brain injury. Many experimental studies have shown the association of apoptosis signal-regulating kinase 1 (ASK1) with cellular pathomechanisms after cerebral ischemia. Blockade of ASK1, by either pharmacological or genetic manipulation, leads to reduced ischemic brain injury and subsequent neuroprotective effects. In this review, we present the cell type-specific pathophysiology of the early phase of ischemic stroke, the role of ASK1 suggested by preclinical studies, and the potential use of ASK suppression, either by pharmacologic or genetic suppression, as a promising therapeutic option for ischemic stroke recovery.

scholarly journals The Protective and Reparative Role of Colony Stimulating Factors in the Brain with Cerebral Ischemia / Reperfusion Injury

2020 ◽  
Author(s):  
Aysha Mohamed Rafik Patel ◽  
Nattayaporn Apaiajai ◽  
Nipon Chattipakorn ◽  
Siriporn Chattipakorn
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Clinical Indication ◽  
Colony Stimulating Factor ◽  
Stroke Therapy ◽  
Post Stroke ◽  
Cerebral Ischemia Reperfusion ◽  
The Brain ◽  
Stimulating Factor

Stroke is a debilitating disease and has the ability to culminate in devastating clinical outcomes. Ischemic stroke followed by reperfusion entrains cerebral ischemia / reperfusion (I/R) injury, which is a complex pathological process and is associated with serious clinical manifestations. Therefore, the development of a robust and effective post-stroke therapy is crucial. Granulocyte colony stimulating factor (GCSF) and erythropoietin (EPO), originally discovered as hematopoietic growth factors, are versatile and have transcended beyond their traditional role of orchestrating the proliferation, differentiation and survival of hematopoietic progenitors to one that fosters brain protection/ neuroregeneration. The clinical indication regarding GCSF and EPO as an auspicious therapeutic strategy is conferred in a plethora of illnesses, including anemia and neutropenia. EPO and GCSF alleviate cerebral I/R injury through a multitude of mechanisms, involving anti-apoptotic, anti-inflammatory, antioxidant, neurogenic and angiogenic effects. Despite bolstering evidence from preclinical studies, the multiple brain protective modalities of GCSF and EPO failed to translate in clinical trials and thereby raises several questions. The present review comprehensively compiles and discusses key findings from in vitro, in vivo and clinical data pertaining to the administration of EPO, GCSF, and other drugs which alter levels of colony stimulating factor (CSF) in the brain following cerebral I/R injury and elaborates on the contributing factors which led to the lost in translation of CSFs from bench to bedside. Any controversial findings are discussed to enable a clear overview of the role of EPO and GCSF as robust and effective candidates for post-stroke therapy.

Energy-requiring cell functions in the ischemic brain

1982 ◽  
Vol 56 (4) ◽  
pp. 482-497 ◽  
Author(s):  
Jens Astrup
Keyword(s):  
Blood Flow ◽  
Cerebral Ischemia ◽  
Global Cerebral Ischemia ◽  
Specific Inhibition ◽  
Ischemic Brain ◽  
Content Type ◽  
Cell Functions ◽  
The Brain ◽  
Fine Print

✓ The energy-requiring cell functions in the brain are described. The role of specific inhibition of these functions, and their critical low-supply levels of blood flow and oxygen are reviewed in relation to clinical management of focal and complete global cerebral ischemia.

Neuroprotection and Angiogenesis: Dual Role of Erythropoietin in Brain Ischemia

Physiology ◽  
2000 ◽  
Vol 15 (5) ◽  
pp. 225-229 ◽  
Author(s):  
Hugo H. Marti ◽  
Myriam Bernaudin ◽  
Edwige Petit ◽  
Christian Bauer
Keyword(s):  
Cerebral Ischemia ◽  
Growth Factor ◽  
Protective Effect ◽  
Brain Tissue ◽  
Brain Ischemia ◽  
Vessel Growth ◽  
The Brain ◽  
Indirect Protection ◽  
Brain Vessel

Erythropoietin, originally defined as an erythroid growth factor, is upregulated in the brain under conditions of hypoxia. So far, two functions have been identified for this locally produced cytokine: a direct protective effect on neuronal cells during cerebral ischemia and an indirect protection of brain tissue that could be provided by promoting brain vessel growth.

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