Skullcapflavone II protects neuronal damage in cerebral ischemic rats via inhibiting NF-ĸB and promoting angiogenesis

Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPARγagonist in that it upregulated PPARγexpression and PPARγ-PPRE binding activity. Administration of curcumin markedly decreased the infarct volume, improved neurological deficits, and reduced neuronal damage of rats. In addition, curcumin suppressed neuroinflammatory response by decreasing inflammatory mediators, such as IL-1β, TNF-α, PGE2, NO, COX-2, and iNOS induced by cerebral ischemia of rats. Furthermore, curcumin suppressed IκB degradation that was caused by cerebral ischemia. The present data also showed that PPARγinteracted with NF-κB-p65 and thus inhibited NF-κB activation. All the above protective effects of curcumin on cerebral ischemic injury were markedly attenuated by GW9662, an inhibitor of PPARγ. Our results as described above suggested that PPARγinduced by curcumin may play a critical role in protecting against brain injury through suppression of inflammatory response. It also highlights the potential of curcumin as a therapeutic agent against cerebral ischemia.

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Combination of Citicoline and L-NAME Restores Neurological Functions, Reverts Biochemical Alterations and Reduces Neuronal Damage in Transient Focal Cerebral Ischemic Rats

Indian Journal of Science and Technology ◽

10.17485/ijst/2015/v8i9/65704 ◽

2015 ◽

Vol 8 (9) ◽

pp. 804

Author(s):

B. Pramila ◽

P. Kalaivani ◽

R. Barathidasan ◽

C. Saravana Babu

Keyword(s):

Neuronal Damage ◽

Biochemical Alterations ◽

Cerebral Ischemic

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LncRNA WT1-AS Attenuates hypoxia/ischemia Induced Neuronal Injury in Cerebral Ischemic Stroke via miR-186-5p/XIAP Axis

10.21203/rs.3.rs-818657/v1 ◽

2021 ◽

Author(s):

Jianquan You ◽

Fei Qian ◽

Yu Huang ◽

Yingxuan Guo ◽

Yaqian Lv ◽

...

Keyword(s):

Ischemic Stroke ◽

Cell Viability ◽

Cell Apoptosis ◽

Neuronal Damage ◽

Luciferase Reporter ◽

Occurrence Rate ◽

Pcr Analysis ◽

Gene Assay ◽

Cerebral Ischemic Stroke ◽

Cerebral Ischemic

Abstract BackgroundCerebral ischemic stroke was a nervous system disease with high occurrence rate and mortality rate. This study aimed to investigate the role and mechanism of lncRNA WT1-AS in cerebral ischemic stroke. Materials and methodsStarbase and dual luciferase reporter gene assay were used to analyze the target relationship between lncRNA WT1-AS and miR-186-5p. qRT-PCR analysis was used to detect lncRNA WT1-AS and miR-186-5p expression. OGD-induced SH-SY5Y cells injury model was conducted, and cell viability and cell apoptosis were determined by MTT and flow cytometer assay. Caspase3 ability was determined using Caspase3 activity detection kit. ResultsmiR-186-5p was a target of lncRNA-WT1-AS. lncRNA WT1-AS was down-regulated and miR-186-5p was up-regulated in blood samples of patients with ischemic stroke and in OGD-induced SH-SY5Y cells. We found that WT1-AS-plasmid promoted OGD-induced cell viability, reduced cell apoptosis and decreased caspase3 ability, and these changes were reversed by miR-186-5p mimic. Subsequently, our results proved that XIAP was a target of miR-186-5p. Similarly, miR-186-5p inhibitor reduced OGD-induced neuronal damage by up-regulating XIAP expression. ConclusionlncRNA-WT1-AS/miR-186-5p/XIAP might be a new target for cerebral ischemic stroke treatment.

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Regulatory mechanism of the SNHG3/miR-302a-3p/E2F1 feedback loop in nerve repair post cerebral ischemic stroke

Current Neurovascular Research ◽

10.2174/1567202618666211210155715 ◽

2021 ◽

Vol 18 ◽

Author(s):

Xiaoyu Sun ◽

Lizhou Wang ◽

Xueqing Huang ◽

Shi Zhou ◽

Tianpeng Jiang

Keyword(s):

Ischemic Stroke ◽

Neuronal Damage ◽

Current Knowledge ◽

Nerve Repair ◽

Related Factors ◽

Tnf Α ◽

Cerebral Ischemic Stroke ◽

Cerebral Ischemic ◽

E2f1 Expression ◽

Brain Tissues

Objective: Cerebral ischemic stroke (CIS) remains a primary cause of death worldwide. The current knowledge has identified the implication of microRNAs (miRNAs) in the pathophysiology of CIS. This study investigated the mechanism of miR-302a-3p in nerve repair post-CIS. Methods: A middle cerebral artery occlusion (MCAO) model was established in mice to simulate CIS. miR-302a-3p expression in brain tissues of MCAO mice was up-regulated by injecting agomiR-302a-3p. The neurological deficit of MCAO mice was evaluated through neurological function score, forelimb placing test, and balance beam walking test. Neuronal damage was measured using Nissl staining. The concentrations of nerve injury-related factors (S100B and GFAP) and the contents of neuroinflammatory factors (TNF-α and IL-1β) in serum were examined using ELISA kits. miR-302a-3p, E2F1, and long non-coding RNA (lncRNA) SNHG3 expressions in brain tissues of MCAO mice were determined using RT-qPCR and Western blot. The binding relationships between miR-302a-3p and E2F1 and E2F1 and SNHG3 were validated using dual-luciferase and ChIP assays, respectively. Results: miR-302a-3p expression was reduced in brain tissues of MCAO mice. miR-302a-3p overexpression increased the number of neurons, decreased the concentrations of S100B and GFAP, reduced the contents of TNF-α and IL-1β, promoted nerve repair, and alleviated CIS-induced brain injury. miR-302a-3p targeted E2F1 expression, and E2F1 activated SNHG3 transcription. E2F1 overexpression or SNHG3 overexpression reversed the effect of miR-302a-3p overexpression on nerve repair in MCAO mice. Conclusion: miR-302a-3p overexpression repressed SNHG3 transcription by targeting E2F1 expression, thereby promoting nerve repair and alleviating CIS.

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Post-ischemic hyperglycemia exacerbates the development of cerebral ischemic neuronal damage through the cerebral sodium-glucose transporter

Brain Research ◽

10.1016/j.brainres.2012.10.020 ◽

2012 ◽

Vol 1489 ◽

pp. 113-120 ◽

Cited By ~ 26

Author(s):

Yui Yamazaki ◽

Shinichi Harada ◽

Shogo Tokuyama

Keyword(s):

Glucose Transporter ◽

Neuronal Damage ◽

Cerebral Ischemic

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Functional, Behavioral, and Histological Changes Induced by Transient Global Cerebral Ischemia in Rats: Effects of Cinnarizine and Flunarizine

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1989.92 ◽

1989 ◽

Vol 9 (5) ◽

pp. 646-654 ◽

Cited By ~ 30

Author(s):

H. Poignet ◽

M. Beaughard ◽

G. Lecoin ◽

R. Massingham

Keyword(s):

Cerebral Ischemia ◽

Neuronal Damage ◽

Global Cerebral Ischemia ◽

Experimental Conditions ◽

Vessel Occlusion ◽

Transient Global Cerebral Ischemia ◽

Behavioral Parameters ◽

Ischemic Episode ◽

Cerebral Ischemic ◽

Positive Effect

Temporary cerebral ischemia (15 min) produced by “four-vessel occlusion” in the rat causes neurological disorders, changes in behavior (locomotor hyperactivity), and neuronal damage in the neocortex, striatum, and especially the CA1 zone of the hippocampus. We have studied the effects of two calcium overload blockers, flunarizine (50 mg/kg p.o. twice a day) and cinnarizine (100 mg/kg p.o. twice a day), on these alterations. Cinnarizine markedly improved the functional abnormalities of ischemia but had little or no effect upon the neuronal damage. In contrast, flunarizine provided far greater neuronal protection but with less obvious effects upon behavioral parameters. However, there was evidence of sedation 2 h after treating animals with this dose of flunarizine that might have masked any positive effect of the drug on behavior. We conclude that under the present experimental conditions, there is no correlation between the early and late behavioral changes observed following a temporary cerebral ischemic episode and the histological damage observed in certain vulnerable neurons, particularly in the hippocampus, 72 h after the insult.

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