Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury

An, Ying; Belevych, Natalya; Wang, Yufen; Zhang, Hao; Nasse, Jason S.; Herschman, Harvey; Chen, Qun; Tarr, A.J.; Liu, Xiaoyu; Quan, Ning

doi:10.2147/jir.s63205

Cited by 4 publications

(3 citation statements)

References 23 publications

(29 reference statements)

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“…Their correlation with neuroinflammation is suggested by a series of seven elected isomeric prostaglandin analogues derived from PGD 2 , PGE 1 , PGE 2 , and PGI 2 . The role of these species and their derivatives in protecting the CNS is widely discussed in the literature, and it is known that they reflect an anti-inflammatory response to neuronal injuries 22 , contributing to neuroprotection in the CNS in the context of excitotoxicity 23 , which is a known contributor to acute brain injury 24 . Recently, Olmo, et al .…”

Section: Inflammation As An Important Player In Impaired Neural Growthmentioning

confidence: 99%

Inflammation markers in the saliva of infants born from Zika-infected mothers: exploring potential mechanisms of microcephaly during fetal development

Oliveira

Lima

Melo

et al. 2019

Sci Rep

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Zika virus (ZIKV) has emerged as one of the most medically relevant viral infections of the past decades; the devastating effects of this virus over the developing brain are a major matter of concern during pregnancy. Although the connection with congenital malformations are well documented, the mechanisms by which ZIKV reach the central nervous system (CNS) and the causes of impaired cortical growth in affected fetuses need to be better addressed. We performed a non-invasive, metabolomics-based screening of saliva from infants with congenital Zika syndrome (CZS), born from mothers that were infected with ZIKV during pregnancy. We were able to identify three biomarkers that suggest that this population suffered from an important inflammatory process; with the detection of mediators associated with glial activation, we propose that microcephaly is a product of immune response to the virus, as well as excitotoxicity mechanisms, which remain ongoing even after birth.

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Section: Inflammation As An Important Player In Impaired Neural Growthmentioning

confidence: 99%

Inflammation markers in the saliva of infants born from Zika-infected mothers: exploring potential mechanisms of microcephaly during fetal development

Oliveira

Lima

Melo

et al. 2019

Sci Rep

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“…In an animal model of excitotoxic brain injury, MRE-269 was found to exert neuroprotective effects 11 , which is a significant finding since excitotoxicity contributes to neuronal death in stroke. There is very limited information regarding the protective mechanisms and the potential to target the IP receptor pathway to reduce stroke injury and improve long-term neurological recovery.…”

Section: Introductionmentioning

confidence: 99%

Sustained Neurological Recovery After Stroke in Aged Rats Treated With a Novel Prostacyclin Analog

Yang

DeMars

Alexander

et al. 2017

Stroke

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Background and Purpose Targeting the prostacyclin/IP receptor to reduce stroke injury has been hindered by the lack of selective drugs. MRE-269 is the active metabolite of selexipag showing a very high selectivity toward the IP receptor. Selexipag has been recently approved for clinical use in pulmonary hypertension. We hypothesized that post-ischemic treatment with MRE-269 provides long-lasting neuroprotection with improved neurological outcomes in a clinically relevant rat stroke model. Methods Aged male Sprague-Dawley rats underwent transient middle cerebral artery occlusion (MCAO) and were randomly selected to receive either vehicle or MRE-269 (0.25 mg/kg) intravenously starting at 4.5h post-ischemia. Accelerating rotarod and adhesive removal tests were conducted before and at 3, 7, 14 and 21 days after stroke. Infarct volume was quantified by MRI at 48h and 21 days post-MCAO. In parallel experiments, cerebral cortex samples from stroke and non-stroke sides from vehicle- and MRE-269-treated groups were collected at 18h post-MCAO for molecular biology analyses. Results Quantitative MRI data showed that post-ischemic MRE-269 treatment significantly reduced infarct volume compared with vehicle-treated rats at both 48 h and three weeks after stroke. MRE-269 treatment resulted in a significant long-term recovery in both locomotor and somatosensory functions following MCAO, which was associated with a reduced weight loss in animals receiving the IP receptor agonist. Post-ischemic MRE-269 treatment reduced pro-inflammatory cytokines/chemokines and oxidative stress. Damage to the blood-brain barrier, as assessed by extravasation of immunoglobulin G to the ischemic brain, was significantly reduced by MRE-269, which was associated with a reduction in matrix metalloproteinase-9 (MMP-9) activity in the brain of stroked aged rats given the IP agonist at 4.5h after ischemia onset. Conclusions Our data suggest that targeting the IP receptor with MRE-269 is a novel strategy to reduce cerebral ischemia injury and promote long-term neurological recovery in ischemic stroke.

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“…PGD 2 , PGE 1 , PGE 2 , and PGI 2 have been correlated with neuroinflammation, protecting the CNS, and physiological responses to minimize further damage to neural tissue. Their anti-inflammatory reaction has been demonstrated in neuronal injuries (Shi et al, 2010) and neuroprotection during acute brain injury (Liang et al, 2005;An et al, 2014) 15d-PGJ 2 activates PPAR-γ by downregulating microglial activation despite the proinflammatory environment because of the neural damage (Bernardo and Minghetti, 2006).…”

Section: The Effect Of Cyclopentenone Prostaglandins On Viral Infection Induced Inflammationmentioning

confidence: 99%

Cyclopentenone Prostaglandins: Biologically Active Lipid Mediators Targeting Inflammation

2021

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Cyclopentenone prostaglandins (cyPGs) are biologically active lipid mediators, including PGA2, PGA1, PGJ2, and its metabolites. cyPGs are essential regulators of inflammation, cell proliferation, apoptosis, angiogenesis, cell migration, and stem cell activity. cyPGs biologically act on multiple cellular targets, including transcription factors and signal transduction pathways. cyPGs regulate the inflammatory response by interfering with NF-κB, AP-1, MAPK, and JAK/STAT signaling pathways via both a group of nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) dependent and PPAR-γ independent mechanisms. cyPGs promote the resolution of chronic inflammation associated with cancers and pathogen (bacterial, viral, and parasitic) infection. cyPGs exhibit potent effects on viral infections by repressing viral protein synthesis, altering viral protein glycosylation, inhibiting virus transmission, and reducing virus-induced inflammation. We summarize their anti-proliferative, pro-apoptotic, cytoprotective, antioxidant, anti-angiogenic, anti-inflammatory, pro-resolution, and anti-metastatic potential. These properties render them unique therapeutic value, especially in resolving inflammation and could be used in adjunct with other existing therapies. We also discuss other α, β -unsaturated carbonyl lipids and cyPGs like isoprostanes (IsoPs) compounds.

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Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury

Cited by 4 publications

References 23 publications

Inflammation markers in the saliva of infants born from Zika-infected mothers: exploring potential mechanisms of microcephaly during fetal development

Inflammation markers in the saliva of infants born from Zika-infected mothers: exploring potential mechanisms of microcephaly during fetal development

Sustained Neurological Recovery After Stroke in Aged Rats Treated With a Novel Prostacyclin Analog

Cyclopentenone Prostaglandins: Biologically Active Lipid Mediators Targeting Inflammation

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