scholarly journals Neuroprotective mechanisms of the ubiquinol action in experimental focal ischemia

2020 ◽  
Vol 66 (2) ◽  
pp. 145-150
Author(s):  
T.N. Fedorova ◽  
V.S. Gusakov ◽  
A.A. Devyatov ◽  
O.A. Muzichuk ◽  
A.V. Lopachev ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Lipid Hydroperoxide ◽  
New Drugs ◽  
Neuroprotective Activity ◽  
Neuroprotective Effects ◽  
The Brain

Ischemic stroke is one of the most socially important diseases characterized by impaired cerebral circulation with focal damage of the brain tissue and decreased functionality. Despite the successes of modern pharmacology, possibilities of pharmacotherapy for stroke remain limited, and the research for new drugs with neuroprotective effects that can prevent brain cell death is still relevant. In this study we have investigated the neuroprotective activity of ubiquinol as a part of an innovative form on a rat model of irreversible 24 h-cerebral ischemia with evaluation of the mechanisms of its neuroprotective effect. Ubiquinol (30 mg/kg), administered intravenously in the acute period of irreversible 24 h focal cerebral ischemia, had a direct neuroprotective effect, characterized by a decrease in the volume of brain tissue necrosis. The protective effect of ubiquinol is due to its ability to inhibit the development of oxidative stress by the direct anti-radical action, preventing the increase in the lipid hydroperoxide content in the brain tissue adjacent to the focus of necrosis, lowering the lipid oxidation rate in plasma against under conditions of increased total antioxidant activity in the brain and blood of experimental animals. In vitro experiments have shown the ability of ubiquinol to prevent cell death in primary culture of cerebral neurons of rat brain under 4 h oxygen/glucose deprivation followed by 20 h reoxygenation.

scholarly journals Neuroprotective Effects of a Novel Inhibitor of c-Jun N-Terminal Kinase in the Rat Model of Transient Focal Cerebral Ischemia

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1860 ◽  
Author(s):  
Mark B. Plotnikov ◽  
Galina A. Chernysheva ◽  
Vera I. Smolyakova ◽  
Oleg I. Aliev ◽  
Eugene S. Trofimova ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Rat Model ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Specific Inhibitor ◽  
Fold Increase ◽  
Neuroprotective Activity ◽  
Prophylactic Regimen ◽  
Neuroprotective Effects

A novel specific inhibitor of c-Jun N-terminal kinase, 11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt (IQ-1S), has a high affinity to JNK3 compared to JNK1/JNK2. The aim of this work was to study the mechanisms of neuroprotective activity of IQ-1S in the models of reversible focal cerebral ischemia (FCI) in Wistar rats. The animals were administered with an intraperitoneal injection of IQ-1S (5 and 25 mg/kg) or citicoline (500 mg/kg). Administration of IQ-1S exerted a pronounced dose-dependent neuroprotective effect, not inferior to the effects of citicoline. Administration of IQ-1S at doses of 5 and 25 mg/kg reduced the infarct size by 20% and 50%, respectively, 48 h after FCI, whereas administration of citicoline reduced the infarct size by 34%. The administration of IQ-1S was associated with a faster amelioration of neurological status. Control rats showed a 2.0-fold increase in phospho-c-Jun levels in the hippocampus compared to the corresponding values in sham-operated rats 4 h after FCI. Administration of IQ-1S at a dose of 25 mg/kg reduced JNK-dependent phosphorylation of c-Jun by 20%. Our findings suggest that IQ-1S inhibits JNK enzymatic activity in the hippocampus and protects against stroke injury when administered in the therapeutic and prophylactic regimen in the rat model of FCI.

scholarly journals Study of the neuroprotective effects of carnosine in an experimental model of focal cerebral ischemia/reperfusion

2018 ◽  
Vol 64 (4) ◽  
pp. 344-348 ◽  
Author(s):  
A.A. Devyatov ◽  
T.N. Fedorova ◽  
S.L. Stvolinsky ◽  
I.N. Ryzhkov ◽  
N.A. Riger ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Experimental Model ◽  
Glutathione Transferase ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Protein Carbonyls ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion

Oxidative stress is one of the key factors in brain tissue damage in ischemia, which indicates the appropriateness of using antioxidants under these conditions. One of the promising antioxidants for the therapy of ischemic stroke is the natural dipeptide carnosine. The neuroprotective effect of dietary carnosine administration was investigated in an experimental model of focal cerebral ischemia/reperfusion in Wistar rats. Animals received carnosine with a diet at a daily dose of 150 mg/kg for 7 days before temporary occlusion of the middle cerebral artery (MCA), performed for 60 min. At 24 h after the onset of ischemia the effect of carnosine on the area of the necrotic core was evaluated in animals. In brain tissue of animals the content of malondialdehyde (MDA), protein carbonyls (PC), total antioxidant capacity (TAC), total activity of superoxide dismutase (SOD), glutathione peroxidase (GP), catalase (CAT) and glutathione transferase (GT), content of isoprostanes and cytokines were measured. Carnosine significantly reduced the infarct size. Carnosine also increased TAC and reduced the level of MDA and isoprostanes in brain tissue. Influence of carnosine on other parameters was not detected. Thus carnosine consumed prophylactically with the diet for 7 days before the induction of ischemia by means of MCA occlusion in rats provides the direct neuroprotective effect, retains high antioxidant activity of brain tissue, reduces the level of oxidative damage markers (MDA and isoprostanes) but does not have any effect on the activity of antioxidant enzyme systems and production of cytokines in brain tissue.

scholarly journals Zingiber officinaleMitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Jintanaporn Wattanathorn ◽  
Jinatta Jittiwat ◽  
Terdthai Tongun ◽  
Supaporn Muchimapura ◽  
Kornkanok Ingkaninan
Keyword(s):  
Cognitive Function ◽  
Cerebral Ischemia ◽  
Brain Damage ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Morris Water Maze Test ◽  
Brain Infarct ◽  
Ginger Rhizome ◽  
The Brain

Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect ofZingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.

scholarly journals A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia

2000 ◽  
Vol XXXII (3-4) ◽  
pp. 76-76
Author(s):  
J. Yrjanheikki ◽  
T. Tikka ◽  
R. Keinanen ◽  
G. Goldsteins ◽  
P. H. Chan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Acute Ischemic Stroke ◽  
Brain Tissue ◽  
Focal Cerebral Ischemia ◽  
The Brain ◽  
Tetracycline Derivative

One of the reasons for the insufficient effectiveness of treatment of acute ischemic stroke may be secondary inflammation of the brain tissue, which, according to the results of modern studies, significantly worsens the consequences and outcome of the disease.

scholarly journals Cerebrovascular and Neuroprotective Effects of Adamantane Derivative

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Ruben S. Mirzoyan ◽  
Tamara S. Gan’shina ◽  
Denis V. Maslennikov ◽  
Georgy I. Kovalev ◽  
Ivan A. Zimin ◽  
...  
Keyword(s):  
Blood Flow ◽  
Nmda Receptors ◽  
Middle Cerebral Artery ◽  
Brain Tissue ◽  
Cerebral Artery ◽  
Brain Ischemia ◽  
Adamantane Derivative ◽  
Neuroprotective Activity ◽  
Neuroprotective Effects ◽  
The Brain

Objectives. The influence of 5-hydroxyadamantane-2-on was studied on the rats’ brain blood flow and on morphological state of brain tissue under the condition of brain ischemia. The interaction of the substance with NMDA receptors was also studied.Methods. Study has been implemented using the methods of local blood flow registration by laser flowmeter, [3H]-MK-801binding, and morphological examination of the brain tissue. We used the models of global transient ischemia of the brain, occlusion of middle cerebral artery, and hypergravity ischemia of the brain.Results. Unlike memantine, antagonist of glutamatergic receptors, the 5-hydroxyadamantane-2-on does not block NMDA receptors but enhances the cerebral blood flow of rats with brain ischemia. This effect is eliminated by bicuculline. Under conditions of permanent occlusion of middle cerebral artery, 5-hydroxyadamantane-2-on has recovered compensatory regeneration in neural cells, axons, and glial cells, and the number of microcirculatory vessels was increased. 5-Hydroxyadamantane-2-on was increasing the survival rate of animals with hypergravity ischemia.Conclusions. 5-Hydroxyadamantane-2-on, an adamantane derivative, which is not NMDA receptors antagonist, demonstrates significant cerebrovascular and neuroprotective activity in conditions of brain ischemia. Presumably, the GABA-ergic system of brain vessels is involved in mechanisms of cerebrovascular and neuroprotective activity of 5-hydroxyadamantane-2-on.

scholarly journals A Nerve Growth Factor Dipeptide Mimetic Stimulates Neurogenesis and Synaptogenesis in the Hippocampus and Striatum of Adult Rats with Focal Cerebral Ischemia

Acta Naturae ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 31-37 ◽  
Author(s):  
T. A. Gudasheva ◽  
P. Yu. Povarnina ◽  
A. A. Volkova ◽  
S. V. Kruglov ◽  
T. A. Antipova ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Cerebral Ischemia ◽  
Growth Factor ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
New Drugs ◽  
Neuroprotective Activity ◽  
Experimental Stroke ◽  
Adult Rats ◽  
Nerve Growth

The nerve growth factor (NGF) and its mimetics, which have neuroprotective and neuroregenerative properties, are attractive candidates for developing new drugs for brain injury therapy. A dipeptide mimetic of NGF loop 4, bis(N-succinyl-L-glutamyl-L-lysine) hexamethylenediamide (GK-2), developed at the Zakusov Research Institute of Pharmacology, has the NGF-like ability to activate TrkA receptors, but unlike NGF, GK-2 activates mainly the PI3K/AKT pathway associated with neuroprotection and has no effect on the MAPK cascade associated with hyperalgesia, the main side effect of NGF. That GK-2 possesses neuroprotective activity has been observed in various models of cerebral ischemia. GK-2 was found to statistically significantly reduce the cerebral infarct volume in experimental stroke, even at treatment onset 24 h after injury. This suggests that GK-2 possesses neuroregenerative properties, which may be associated with the activation of neurogenesis and/or synaptogenesis. We studied the effect of GK-2 on neurogenesis and synaptogenesis in experimental ischemic stroke caused by transient occlusion of the middle cerebral artery in rats. GK-2 was administered 6 or 24 h after surgery and then once a day for 7 days. One day after the last administration, proliferative activity in the hippocampus and striatum of the affected hemisphere was assessed using Ki67 and synaptogenesis in the striatum was evaluated using synaptophysin and PSD-95. Ki67 immunoreactivity, both in the striatum and in the hippocampus of the ischemic rats, was found to have dropped by approximately 30% compared to that in the sham-operated controls. Synaptic markers - synaptophysin and PSD-95 - were also statistically significantly reduced, by 14 and 29%, respectively. GK-2 in both administration schedules completely restored the level of Ki67 immunoreactivity in the hippocampus and promoted its increase in the striatum. In addition, GK-2 restored the level of the postsynaptic marker PSD-95, with the therapeutic effect amounting to 70% at the start of its administration after 6 h, and promoted restoration of the level of this marker at the start of administration 24 h after an experimental stroke. GK-2 had no effect on the synaptophysin level. These findings suggest that the neurotrophin mimetic GK-2, which mainly activates one of the main Trk receptor signaling pathways PI3K/ AKT, has a stimulating effect on neurogenesis (and, probably, gliogenesis) and synaptogenesis in experimental cerebral ischemia. This effect may explain the protective effect observed at the start of dipeptide administration 24 h after stroke simulation.

The protective effect of lipophilic iron chelator 2, 2′-dipyridyl after focal cerebral ischemia closely correlates with limitation of apoptotic cell death

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S482-S482
Author(s):  
Michaël C Van Hoecke ◽  
Anne Prigent-Tessier ◽  
Philippe E Garnier ◽  
Christine Marie ◽  
Alain Beley
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Protective Effect ◽  
Apoptotic Cell ◽  
Focal Cerebral Ischemia ◽  
Iron Chelator ◽  
Apoptotic Cell Death
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