Pterostilbene alleviates cerebral ischemia and reperfusion injury in rats by modulating microglial activation

Hou, Yue; Xu, Jikai; Mi, Yan; Yang, Yanqiu; Li, Qing; Zhou, Di; Wei, Kun; Chen, Gang; Li, Ning; Hou, Yue

doi:10.1039/d0fo00084a

Cited by 29 publications

(27 citation statements)

References 46 publications

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Section: Discussionmentioning

confidence: 99%

Neuroprotective effect of Indobufen against pyroptosis following cerebral ischemia-reperfusion injury both in vivo and in vitro

Tian

et al. 2020

Preprint

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Background: Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, the efficacy of Indobufen on cerebral ischemia/reperfusion (I/R) injury and its mechanisms remain to be investigated. Methods: In this study, the efficacy of Indobufen with both pre- (5days) and post- (15days) treatment on rats suffering middle cerebral artery occlusion/reperfusion (MCAO/R, 2h of ischemia and 24h/15days of reperfusion) was investigated. Furthermore, human umbilical vein endothelial cells (HUVECs) were cultured and underwent oxygen glucose deprivation/reoxygenation (OGD/R) injury for in vitro studies. Relationship between Indobufen and pyroptosis associated NF-κB/Caspase-1/GSDMD pathway was preliminarily discussed. Results: The pharmacodynamic tests revealed that Indobufen ameliorated I/R injury by decreasing the platelet aggregation, infarct size, brain edema and neurologic impairment in rats and rescuing cell apoptosis/pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by platelet inhibition induced regulation of the NF-κB/Caspase-1/GSDMD pathway. Conclusion: Overall, these studies indicates that Indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective effect of Indobufen against pyroptosis following cerebral ischemia-reperfusion injury both in vivo and in vitro

Tian

et al. 2020

Preprint

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“…After ischemic stroke, IκB is phosphorylated and degraded, causing NF-κB p65 translocation from the cytoplasm to the nucleus, promoting the transcription of a number of genes, such as IL-1β [31]. Moreover, latest research provided new evidence that ROS is related to platelet and in ammatory pyroptosis activation [32] and is able to regulate NF-κB as a second messenger [33,34]. Caspase-1 can be stimulated by the typical signal of NF-κB-p65 entry into the nucleus and is activated by canonical in ammasomes such as NLRP3, which promotes brain tissue damage [8].…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effect of Indobufen against pyroptosis following cerebral ischemia-reperfusion injury both in vivo and in vitro

Tian

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, the efficacy of Indobufen on cerebral ischemia/reperfusion (I/R) injury and its mechanisms remain to be investigated. Methods: In this study, the efficacy of Indobufen with both pre- (5days) and post- (15days) treatment on rats suffering middle cerebral artery occlusion/reperfusion (MCAO/R, 2h of ischemia and 24h/15days of reperfusion) was investigated. Furthermore, human umbilical vein endothelial cells (HUVECs) were cultured and underwent oxygen glucose deprivation/reoxygenation (OGD/R) injury for in vitro studies. Relationship between Indobufen and pyroptosis associated NF-κB/Caspase-1/GSDMD pathway was preliminarily discussed. Results: The pharmacodynamic tests revealed that Indobufen ameliorated I/R injury by decreasing the platelet aggregation, infarct size, brain edema and neurologic impairment in rats and rescuing cell apoptosis/pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by platelet inhibition induced regulation of the NF-κB/Caspase-1/GSDMD pathway.Conclusion: Overall, these studies indicates that Indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.

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“…Though calcitriol has shown neuroprotective effects in experimental models of IS [77][78][79], our human data might point to loss of efficacy outside of an early time window. Pterostilbene, an antioxidant, anti-inflammatory and anti-apoptotic compound with a beneficial effect after stroke [80][81][82][83], was predicted as an upstream regulator of the observed changes in neutrophil gene expression but only at times >48h after IS.…”

Section: Gene Expression Dynamics After Ischemic Strokementioning

confidence: 99%

Monocyte, Neutrophil and Whole Blood Transcriptome Dynamics Following Ischemic Stroke

Carmona-Mora

Knepp

Jickling

et al. 2022

Preprint

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BackgroundAfter ischemic stroke (IS), peripheral leukocytes infiltrate the damaged region and modulate the response to injury. Peripheral blood cells display distinctive gene expression signatures post IS and these transcriptional programs reflect changes in immune responses to IS. Dissecting the temporal dynamics of gene expression after IS improves our understanding of immune and clotting responses at the molecular and cellular level that are involved in acute brain injury and may assist with time-targeted, cell-specific therapy.MethodsThe transcriptomic profiles from peripheral monocytes, neutrophils, and whole blood from 38 ischemic stroke patients and 18 controls were analyzed with RNAseq as a function of time and etiology after stroke. Differential expression analyses were performed at 0-24 h, 24-48 h, and >48 h following stroke.ResultsUnique patterns of temporal gene expression and pathways were distinguished for monocytes, neutrophils and whole blood with enrichment of interleukin signaling pathways for different timepoints and stroke etiologies. Compared to control subjects, gene expression was generally up-regulated in neutrophils and generally down- regulated in monocytes over all times for cardioembolic, large vessel and small vessel strokes. Self-Organizing Maps identified gene clusters with similar trajectories of gene expression over time for different stroke causes and sample types. Weighted Gene Co- expression Network Analyses identified modules of co-expressed genes that significantly varied with time after stroke and included hub genes of immunoglobulin genes in whole blood.ConclusionsAltogether, the identified genes and pathways are critical for understanding how the immune and clotting systems change over time after stroke. This study identifies potential time- and cell-specific biomarkers and treatment targets.

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Pterostilbene alleviates cerebral ischemia and reperfusion injury in rats by modulating microglial activation

Abstract: The study demonstrates the mechanism of pterostilbene alleviating cerebral ischemia and reperfusion injury in rats may associate with the inhibition of ROS/NF-κB-mediated inflammatory pathway.

Cited by 29 publications

References 46 publications

Neuroprotective effect of Indobufen against pyroptosis following cerebral ischemia-reperfusion injury both in vivo and in vitro

Neuroprotective effect of Indobufen against pyroptosis following cerebral ischemia-reperfusion injury both in vivo and in vitro

Neuroprotective effect of Indobufen against pyroptosis following cerebral ischemia-reperfusion injury both in vivo and in vitro

Monocyte, Neutrophil and Whole Blood Transcriptome Dynamics Following Ischemic Stroke

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