Interaction of free radicals, matrix metalloproteinases and caveolin-1 impacts blood-brain barrier permeability

Gu, Yong; Dee, Cathleen Michelle; Shen, Jiangang

doi:10.2741/222

Cited by 142 publications

(92 citation statements)

References 156 publications

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“…Cav-1 regulates expression of junction-associated proteins in brain microvascular endothelial cells, and attenuated Cav-1 levels are correlated with heightened permeability of endothelia [14]. In addition, Cav-1 knockout mice present higher vascular permeability, which has been found to aggravate disorders in rodent models [15,16]. Although the exact role of Cav-1 in SCI remains unclear, it is plausible that Cav-1 is a critical mediator of BSCB integrity.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood–Spinal Cord Barrier and Functional Recovery

Xia

et al. 2016

Neurotherapeutics

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The blood-spinal cord barrier (BSCB) plays important roles in the recovery of spinal cord injury (SCI), and caveolin-1 is essential for the integrity and permeability of barriers. Basic fibroblast growth factor (bFGF) is an important neuroprotective protein and contributes to the survival of neuronal cells. This study was designed to investigate whether bFGF is beneficial for the maintenance of junction proteins and the integrity of the BSCB to identify the relations with caveolin-1 regulation. We examined the integrity of the BSCB with Evans blue dye and fluorescein isothiocyanate-dextran extravasation, measured the junction proteins and matrix metalloproteinases, and evaluated the locomotor function recovery. Our data indicated that bFGF treatment improved the recovery of BSCB and functional locomotion in contusive SCI model rats, reduced the expression and activation of matrix metalloproteinase-9, and increased the expressions of caveolin-1 and junction proteins, including occludin, claudin-5, p120-catenin, and β-catenin. In the brain, in microvascular endothelial cells, bFGF treatment increased the levels of junction proteins, caveolin-1 small interfering RNA abolished the protective effect of bFGF under oxygen-glucose deprivation conditions, and the expression of fibroblast growth factor receptor 1 and co-localization with caveolin-1 decreased significantly, which could not be reversed by bFGF treatment. These findings provide a novel mechanism underlying the beneficial effects of bFGF on the BSCB and recovery of SCI, especially the regulation of caveolin-1.

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Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood–Spinal Cord Barrier and Functional Recovery

Xia

et al. 2016

Neurotherapeutics

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“…88,89 Indeed, infarct size is larger in cav-1 knockout mice. 88 After brain ischemia, cav-1 is decreased and correlates with an increase in brain MMP-2 and BBB permeability. 89 In cultured endothelial cells, inhibition of cav-1 with siRNA alters the distribution of the TJP claudin-5 in response to oxygen glucose deprivation.…”

Section: Early and Delayed Hemorrhagic Transformationmentioning

confidence: 99%

Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

Jickling

Liu

Stamova

et al. 2013

J Cereb Blood Flow Metab

450

369

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Hemorrhagic transformation (HT) is a common complication of ischemic stroke that is exacerbated by thrombolytic therapy. Methods to better prevent, predict, and treat HT are needed. In this review, we summarize studies of HT in both animals and humans. We propose that early HT (o18 to 24 hours after stroke onset) relates to leukocyte-derived matrix metalloproteinase-9 (MMP-9) and brain-derived MMP-2 that damage the neurovascular unit and promote blood-brain barrier (BBB) disruption. This contrasts to delayed HT (418 to 24 hours after stroke) that relates to ischemia activation of brain proteases (MMP-2, MMP-3, MMP-9, and endogenous tissue plasminogen activator), neuroinflammation, and factors that promote vascular remodeling (vascular endothelial growth factor and high-moblity-group-box-1). Processes that mediate BBB repair and reduce HT risk are discussed, including transforming growth factor beta signaling in monocytes, Src kinase signaling, MMP inhibitors, and inhibitors of reactive oxygen species. Finally, clinical features associated with HT in patients with stroke are reviewed, including approaches to predict HT by clinical factors, brain imaging, and blood biomarkers. Though remarkable advances in our understanding of HT have been made, additional efforts are needed to translate these discoveries to the clinic and reduce the impact of HT on patients with ischemic stroke.

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“…The accumulation of ROS is known to increase the susceptibility of brain tissue to damage. They also trigger numerous molecular cascades, leading to increased blood-brain barrier permeability (through activation of matrix metalloproteinases and subsequently degradation of tight junctions), alterations of brain morphology, neuroinflammation, and neuronal death (61).…”

Section: The Link Between Sls Brain Oxidative Stress and The Develomentioning

confidence: 99%

Severe Life Stress and Oxidative Stress in the Brain: From Animal Models to Human Pathology

Schiavone

Jaquet

Trabace

et al. 2013

Antioxidants & Redox Signaling

280

211

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Significance: Severe life stress (SLS), as opposed to trivial everyday stress, is defined as a serious psychosocial event with the potential of causing an impacting psychological traumatism. Recent Advances: Numerous studies have attempted to understand how the central nervous system (CNS) responds to SLS. This response includes a variety of morphological and neurochemical modifications; among them, oxidative stress is almost invariably observed. Oxidative stress is defined as disequilibrium between oxidant generation and the antioxidant response. Critical Issues: In this review, we discuss how SLS leads to oxidative stress in the CNS, and how the latter impacts pathophysiological outcomes. We also critically discuss experimental methods that measure oxidative stress in the CNS. The review covers animal models and human observations. Animal models of SLS include sleep deprivation, maternal separation, and social isolation in rodents, and the establishment of hierarchy in non-human primates. In humans, SLS, which is caused by traumatic events such as child abuse, war, and divorce, is also accompanied by oxidative stress in the CNS. Future Directions: The outcome of SLS in humans ranges from resilience, over post-traumatic stress disorder, to development of chronic mental disorders. Defining the sources of oxidative stress in SLS might in the long run provide new therapeutic avenues.

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Interaction of free radicals, matrix metalloproteinases and caveolin-1 impacts blood-brain barrier permeability

Cited by 142 publications

References 156 publications

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood–Spinal Cord Barrier and Functional Recovery

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood–Spinal Cord Barrier and Functional Recovery

Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

Severe Life Stress and Oxidative Stress in the Brain: From Animal Models to Human Pathology

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