Sulforaphane induces neurovascular protection against a systemic inflammatory challenge via both Nrf2-dependent and independent pathways

Holloway, Paul M.; Gillespie, Scarlett; Becker, Felix; Vital, SA; Nguyen,; Alexander, JS; Evans, Paul C.; Gavins, Felicity N. E.

doi:10.1016/j.vph.2016.07.004

Cited by 33 publications

(32 citation statements)

References 40 publications

(67 reference statements)

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“…Sulforaphane (SFN), a well-known NRF2 promoter/activator, is an organic isothiocyanate naturally found in cruciferous plants such as broccoli and cabbage. SFN has been shown to possess neuroprotective properties in vitro as well as in vivo by activating the NRF2-KEAP1 pathway and enhancing the corresponding protein synthesis [122,[131][132][133][134][135][136][137][138][139]. Several studies revealed that in addition to the activation of NRF2, SFN could independently inhibit NF-kB activity.…”

Section: Current Treatments Of Tbimentioning

confidence: 99%

Traumatic Brain Injury and Blood–Brain Barrier (BBB): Underlying Pathophysiological Mechanisms and the Influence of Cigarette Smoking as a Premorbid Condition

Sivandzade

Alqahtani

Cucullo

2020

IJMS

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Traumatic brain injury (TBI) is among the most pressing global health issues and prevalent causes of cerebrovascular and neurological disorders all over the world. In addition to the brain injury, TBI may also alter the systemic immune response. Thus, TBI patients become vulnerable to infections, have worse neurological outcomes, and exhibit a higher rate of mortality and morbidity. It is well established that brain injury leads to impairments of the blood–brain barrier (BBB) integrity and function, contributing to the loss of neural tissue and affecting the response to neuroprotective drugs. Thus, stabilization/protection of the BBB after TBI could be a promising strategy to limit neuronal inflammation, secondary brain damage, and acute neurodegeneration. Herein, we present a review highlighting the significant post-traumatic effects of TBI on the cerebrovascular system. These include the loss of BBB integrity and selective permeability, impact on BBB transport mechanisms, post-traumatic cerebral edema formation, and significant pathophysiological factors that may further exacerbate post-traumatic BBB dysfunctions. Furthermore, we discuss the post-traumatic impacts of chronic smoking, which has been recently shown to act as a premorbid condition that impairs post-TBI recovery. Indeed, understanding the underlying molecular mechanisms associated with TBI damage is essential to better understand the pathogenesis and progression of post-traumatic secondary brain injury and the development of targeted treatments to improve outcomes and speed up the recovery process. Therapies aimed at restoring/protecting the BBB may reduce the post-traumatic burden of TBI by minimizing the impairment of brain homeostasis and help to restore an optimal microenvironment to support neuronal repair.

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Section: Current Treatments Of Tbimentioning

confidence: 99%

Traumatic Brain Injury and Blood–Brain Barrier (BBB): Underlying Pathophysiological Mechanisms and the Influence of Cigarette Smoking as a Premorbid Condition

Sivandzade

Alqahtani

Cucullo

2020

IJMS

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“…3), indicating a profound inflammatory response, possibly through increased expression of endothelial adhesion molecules [6, 11, 21]. Thus, we provide an additional evidence for the role of Nrf2 and importantly, ABCB10, in protection of BBB endothelium against inflammation.…”

Section: Discussionmentioning

confidence: 66%

Blood-brain barrier disruption in diabetic mice is linked to Nrf2 signaling deficits: Role of ABCB10?

Sajja

Prasad

Tang

et al. 2017

Neuroscience Letters

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Blood-brain barrier (BBB) damage is a critical neurovascular complication of diabetes mellitus that adversely affects the CNS health and function. Previously, we showed the protective role of NF-E2 related factor-2 (Nrf2), a redox sensitive transcription factor, in regulation of BBB integrity. Given the pathogenic role of mitochondrial oxidative stress in diabetes-related microvascular complications, we focused on assessing: 1) the impact of diabetes on brain Nrf2 in correlation with BBB permeability and 2) Nrf2-dependent regulation of the mitochondrial transporter ABCB10, an essential player in mitochondrial function and redox balance at BBB endothelium. Using live animal fluorescence imaging, we demonstrated a strong increase in BBB permeability to 70kDa dextran in db/db diabetic mice that correlated with significant down-regulation of brain Nrf2 protein. Further, Nrf2 gene silencing in human BBB endothelial cells markedly suppressed ABCB10 protein, while Nrf2 activation by sulforaphane up-regulated ABCB10 expression. Interestingly, ABCB10 knockdown resulted in a strong-induction of Nrf2 driven anti-oxidant responses as evidenced by increased expression of Nrf2 and its downstream targets. Nrf2 or ABCB10 silencing elevated endothelial-monocyte adhesion suggesting an activated inflammatory cascade. Thus, our results demonstrate a novel mechanism of ABCB10 regulation driven by Nrf2. In summary, Nrf2 dysregulation and ABCB10 suppression could likely mediate endothelial oxidative/inflammatory stress and BBB disruption in diabetic subjects.

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“…Along with other beneficial effects of SFN, such as anti-inflammation [88]. Multiple in vitro and in vivo studies have demonstrated the ability of SFN to prevent various brain diseases, including stroke, TBI, AD, PD, and ASD.…”

Section: Resultsmentioning

confidence: 99%

“…Because of its BBB permeability, SFN can reach effective concentration in the CNS. Considering its other beneficial effects, such as anti-inflammation [88], SFN is a promising dietary and medical agent for neuroprotection.…”

Section: Resultsmentioning

confidence: 99%

Sulforaphane Protects against Brain Diseases: Roles of Cytoprotective Enzymes

Zhang¹

2017

Austin J Cerebrovasc Dis & Stroke

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Sulforaphane (SFN) is a kind of isothiocyanate derived from broccoli and other cruciferous vegetables. Because of its roles of antioxidant, anti-inflammatory, and anti-tumor through multiple targets and various mechanisms, SFN has drawn broad attention of the researchers. One of the most important target of SFN is nuclear factor erythroid 2 related factor 2 (Nrf2), wildly known for its ability to regulate the expression of a series of cytoprotective enzymes with antioxidative, prosurvival, and detoxification effects. Multiple researches have shown that SFN protects against central nervous system diseases through Nrf2pathway. In this article, we list SFN contents in common cruciferous vegetables, and summarize recent advances in the protective effects of SFN against acute brain injuries and neurodegenerative diseases through activating Nrf2 signaling pathway.

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Sulforaphane induces neurovascular protection against a systemic inflammatory challenge via both Nrf2-dependent and independent pathways

Cited by 33 publications

References 40 publications

Traumatic Brain Injury and Blood–Brain Barrier (BBB): Underlying Pathophysiological Mechanisms and the Influence of Cigarette Smoking as a Premorbid Condition

Traumatic Brain Injury and Blood–Brain Barrier (BBB): Underlying Pathophysiological Mechanisms and the Influence of Cigarette Smoking as a Premorbid Condition

Blood-brain barrier disruption in diabetic mice is linked to Nrf2 signaling deficits: Role of ABCB10?

Sulforaphane Protects against Brain Diseases: Roles of Cytoprotective Enzymes

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