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 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.

Therapeutic Neuroprotective Effects of XQ-1H in a Rat Model of Permanent Focal Cerebral Ischemia

Pharmacology ◽  
2012 ◽  
Vol 89 (1-2) ◽  
pp. 1-6 ◽  
Author(s):  
Qichuan Yang ◽  
Weirong Fang ◽  
Peng Lv ◽  
Xiaohan Geng ◽  
Yunman Li ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Rat Model ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effects

scholarly journals Sustained Blockade of Brain AT1 Receptors before and after Focal Cerebral Ischemia Alleviates Neurologic Deficits and Reduces Neuronal Injury, Apoptosis, and Inflammatory Responses in the Rat

2004 ◽  
Vol 24 (5) ◽  
pp. 536-547 ◽  
Author(s):  
Min Lou ◽  
Annegret Blume ◽  
Yi Zhao ◽  
Peter Gohlke ◽  
Günther Deuschl ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Inflammatory Responses ◽  
Focal Cerebral Ischemia ◽  
At1 Receptor ◽  
Neuroprotective Effects ◽  
Reactive Microglia ◽  
At1 Receptors ◽  
Before And After

In the present study, we investigate whether a long-term blockade of brain AT1 receptors in male Wistar rats before and after ischemic injury exerts neuroprotective effects and modulates apoptosis and inflammatory responses, which are associated with the post-ischemic progression of brain damage. The AT1 receptor antagonist irbesartan was continuously infused intracerebroventricularly using osmotic minipumps over a 5-day period before and for 3 or 7 days after middle cerebral artery occlusion (MCAO) for 90 minutes. Neurologic status was evaluated daily, starting 24 hours after MCAO. After MCAO (3 and 7 days), brains were removed for the measurement of infarct size and immunohistochemical evaluation of apoptosis and accumulation of reactive microglia and macrophages. Treatment with irbesartan before ischemia improved motor functions, whereas post-ischemic treatment improved sensory functions. Blockade of brain AT1 receptors reduced the infarct size on days 3 and 7 after MCAO. In the peri-infarct cortex, irbesartan treatment decreased the number of apoptotic cells on day 3 and attenuated the invasion of activated microglia and macrophages on days 3 and 7 after ischemia. Long-term blockade of brain AT1 receptors improves the recovery from cerebral ischemia. Antiapoptotic mechanisms and inhibition of post-ischemic inflammation are involved in the AT1 receptor blockade-induced neuroprotective effects in ischemic brain tissue.

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