Efficacy of prophylactic flavan-3-ol in permanent focal ischemia in 12-mo-old mice

Leonardo, Christopher C.; Mendes, Monique; Ahmad, Abdullah Shafique; Doré, Sylvain

doi:10.1152/ajpheart.00239.2014

Cited by 8 publications

(10 citation statements)

References 66 publications

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“…EC-treated ischemic WT mice displayed a reduction of forelimb motor coordination impairments associated with reduced anatomical injury and microglia/macrophage activation in pMCAO and tMCAO models of adult WT mice, impairments which were abolished in tissues and neurons from Nrf2 −/− mice (Shah et al, 2010 ). Interestingly, this neuroprotection was observed in 12 month-old WT and Nrf2 −/− mice, indicating that age influences Nrf2 function (Leonardo et al, 2013 , 2015 ).…”

Section: Nrf2 Targeted Intervention In Ischemic Stroke—advancements Fmentioning

confidence: 95%

“…Multiple lines of evidence demonstrate the beneficial contribution of Nrf2 in various pathological conditions, and most come from studies using Nrf2 knockout (Nrf2 −/− ) or knockdown animals. Reports showed that Nrf2 −/− mice do not exhibit any overt abnormal phenotype regarding size, body weight, food intake, mobility, fertility, or other characteristics at baseline (Itoh et al, 1997 ; Wang et al, 2007 ; Wang Y. C. et al, 2011 ; Wang B. et al, 2012 ; Leonardo et al, 2013 , 2015 ; Doré, 2015 ; Liu et al, 2018 ). In addition, Nrf2 −/− mice exhibit similar cerebrovascular architecture in anastomosis, vascular physiology, and blood pH compared to their WT counterparts (Leonardo et al, 2015 ).…”

Section: Functional Benefit Of Nrf2 In Cerebral Ischemia— Imentioning

confidence: 99%

“…Reports showed that Nrf2 −/− mice do not exhibit any overt abnormal phenotype regarding size, body weight, food intake, mobility, fertility, or other characteristics at baseline (Itoh et al, 1997 ; Wang et al, 2007 ; Wang Y. C. et al, 2011 ; Wang B. et al, 2012 ; Leonardo et al, 2013 , 2015 ; Doré, 2015 ; Liu et al, 2018 ). In addition, Nrf2 −/− mice exhibit similar cerebrovascular architecture in anastomosis, vascular physiology, and blood pH compared to their WT counterparts (Leonardo et al, 2015 ). Basal GST and NQO1 activities, but not GSH content, modestly but significantly decreased in multiple brain regions of Nrf2 −/− mice compared to their Nrf2 +/+ littermates, suggesting that the constitutive synthesis of brain GSH does not rely on Nrf2 function, at least in young adult mice (Shih et al, 2005 ).…”

Section: Functional Benefit Of Nrf2 In Cerebral Ischemia— Imentioning

confidence: 99%

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Critical Role of Nrf2 in Experimental Ischemic Stroke

2019

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Ischemic stroke is one of the leading causes of death and long-term disability worldwide; however, effective clinical approaches are still limited. The transcriptional factor Nrf2 is a master regulator in cellular and organismal defense against endogenous and exogenous stressors by coordinating basal and stress-inducible activation of multiple cytoprotective genes. The Nrf2 network not only tightly controls redox homeostasis but also regulates multiple intermediary metabolic processes. Therefore, targeting Nrf2 has emerged as an attractive therapeutic strategy for the prevention and treatment of CNS diseases including stroke. Here, the current understanding of the Nrf2 regulatory network is critically examined to present evidence for the contribution of Nrf2 pathway in rodent ischemic stroke models. This review outlines the literature for Nrf2 studies in preclinical stroke and focuses on the in vivo evidence for the role of Nrf2 in primary and secondary brain injuries. The dynamic change and functional importance of Nrf2 signaling, as well as Nrf2 targeted intervention, are revealed in permanent, transient, and global cerebral ischemia models. In addition, key considerations, pitfalls, and future potentials for Nrf2 studies in preclinical stroke investigation are discussed.

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Section: Nrf2 Targeted Intervention In Ischemic Stroke—advancements Fmentioning

confidence: 95%

Section: Functional Benefit Of Nrf2 In Cerebral Ischemia— Imentioning

confidence: 99%

Section: Functional Benefit Of Nrf2 In Cerebral Ischemia— Imentioning

confidence: 99%

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Critical Role of Nrf2 in Experimental Ischemic Stroke

2019

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“…Traditionally, microglia were considered a homogeneous population, which was supported by the fact that they originated from a uniform progenitor pool that invaded the brain early in development and populated all brain regions. Although differences in morphology between white and gray matter microglia were appreciated in early studies (Del Rio‐Hortega, 1932; Easley‐Neal et al., 2019; Lawson et al., 1990), only recently has there been a renewed interest in understanding microglial heterogeneity. It is becoming clear that microglial distribution differs by brain region and that microglial morphology is remarkably fluid, changing both during physiological conditions and injury.…”

Section: Distinct Subtypes Of Microglia May Have Specific Roles In Different Brain Areas and Developmental Time Periodsmentioning

confidence: 99%

An overview of microglia ontogeny and maturation in the homeostatic and pathological brain

Mendes

Majewska

2021

Eur J of Neuroscience

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Microglia are the resident immune cells of the central nervous system (CNS) and are increasingly recognized as critical players in development, brain homeostasis, and disease pathogenesis. The lifespan, maintenance, proliferation, and turnover of microglia are important factors that regulate microglial behavior and affect their roles in the CNS. However, emerging evidence suggests that microglia are morphologically and phenotypically distinct in different brain areas, at different ages, and during disease. Ongoing research focuses on understanding how microglia acquire specific phenotypes in response to extrinsic cues in the environment and how phenotypes are specified by intrinsic properties of different populations of microglia. With the development of pharmacological and genetic tools that allow the investigation of microglia in vivo, there have been considerable advances in understanding molecular signatures of both homeostatic microglia and those reacting to injury and disease. Here, we review the master gene regulators that define microglia as well as discuss the evidence that microglia are heterogeneous and fall into distinct clusters that display specific intrinsic properties and perform unique tasks in different settings. Taken together, the information presented supports the idea that microglia morphology and transcriptional heterogeneity should be considered when studying the complex nature of microglia and their roles in brain health and disease.

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“…This result indicated that Nrf2 modulated protection in the aging phenotype at least in part, but that with aging, the action of Nrf2 is weak. However, EC treatment did not alter microglia activation, vascular permeability or spontaneous hemorrhage [ 31 ].…”

Section: Natural Compounds As Modulator Of Nrf2 Pathway In Stroke mentioning

confidence: 99%

Activation of Nrf2 by Natural Bioactive Compounds: A Promising Approach for Stroke?

Gugliandolo

Bramantı

Mazzon

2020

IJMS

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Stroke represents one of the main causes of disability and death worldwide. The pathological subtypes of stroke are ischemic stroke, the most frequent, and hemorrhagic stroke. Nrf2 is a transcription factor that regulates redox homeostasis. In stress conditions, Nrf2 translocates inside the nucleus and induces the transcription of enzymes involved in counteracting oxidative stress, endobiotic and xenobiotic metabolism, regulators of inflammation, and others. Different natural compounds, including food and plant-derived components, were shown to be able to activate Nrf2, mediating an antioxidant response. Some of these compounds were tested in stroke experimental models showing several beneficial actions. In this review, we focused on the studies that evidenced the positive effects of natural bioactive compounds in stroke experimental models through the activation of Nrf2 pathway. Interestingly, different natural compounds can activate Nrf2 through multiple pathways, inducing a strong antioxidant response associated with the beneficial effects against stroke. According to several studies, the combination of different bioactive compounds can lead to a better neuroprotection. In conclusion, natural bioactive compounds may represent new therapeutic strategies against stroke.

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Efficacy of prophylactic flavan-3-ol in permanent focal ischemia in 12-mo-old mice

Abstract: Leonardo CC, Mendes M, Ahmad AS, Doré S. Efficacy of prophylactic flavan-3-ol in permanent focal ischemia in 12-mo-old mice.

Cited by 8 publications

References 66 publications

Critical Role of Nrf2 in Experimental Ischemic Stroke

Critical Role of Nrf2 in Experimental Ischemic Stroke

An overview of microglia ontogeny and maturation in the homeostatic and pathological brain

Activation of Nrf2 by Natural Bioactive Compounds: A Promising Approach for Stroke?

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