The role of NADPH oxidase in blood -brain barrier dysfunction following stroke in aged rats

It is well-known that stroke is one of the leading causes of death and disability all over the world. After a stroke, the blood-brain barrier subsequently breaks down. The BBB consists of endothelial cells surrounded by astrocytes. Microglia, considered the long-living resident immune cells of the brain, play a vital role in BBB function. M1 microglia worsen BBB disruption, while M2 microglia assist in repairing BBB damage. Microglia can also directly interact with endothelial cells and affect BBB permeability. In this review, we are going to discuss the mechanisms responsible for the dual role of microglia in BBB dysfunction after stroke.

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Role of endothelial TRPA1 expression in blood‐brain barrier dysfunction

Alzheimer s & Dementia ◽

10.1002/alz.058550 ◽

2021 ◽

Vol 17 (S2) ◽

Author(s):

Euitaek Yang ◽

Amal Kaddoumi

Keyword(s):

Blood Brain Barrier ◽

Brain Barrier ◽

Barrier Dysfunction ◽

Blood Brain

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The Role of Brain Microvascular Endothelial Cell and Blood-Brain Barrier Dysfunction in Schizophrenia

Complex Psychiatry ◽

10.1159/000511552 ◽

2020 ◽

Vol 6 (1-2) ◽

pp. 30-46

Author(s):

Sovannarath Pong ◽

Rakesh Karmacharya ◽

Marianna Sofman ◽

Jeffrey R. Bishop ◽

Paulo Lizano

Keyword(s):

Blood Brain Barrier ◽

Association Studies ◽

Central Element ◽

Brain Barrier ◽

Microvascular Endothelial Cell ◽

Genome Wide Association Studies ◽

Barrier Dysfunction ◽

Blood Brain ◽

Microvascular Endothelial

Background: Despite decades of research, little clarity exists regarding pathogenic mechanisms related to schizophrenia. Investigations on the disease biology of schizophrenia have primarily focused on neuronal alterations. However, there is substantial evidence pointing to a significant role for the brain’s microvasculature in mediating neuroinflammation in schizophrenia. Summary: Brain microvascular endothelial cells (BMEC) are a central element of the microvasculature that forms the blood-brain barrier (BBB) and shields the brain against toxins and immune cells via paracellular, transcellular, transporter, and extracellular matrix proteins. While evidence for BBB dysfunction exists in brain disorders, including schizophrenia, it is not known if BMEC themselves are functionally compromised and lead to BBB dysfunction. Key Messages: Genome-wide association studies, postmortem investigations, and gene expression analyses have provided some insights into the role of the BBB in schizophrenia pathophysiology. However, there is a significant gap in our understanding of the role that BMEC play in BBB dysfunction. Recent advances differentiating human BMEC from induced pluripotent stem cells (iPSC) provide new avenues to examine the role of BMEC in BBB dysfunction in schizophrenia.

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1958-P: Role of Leptin in Blood-Brain Barrier Dysfunction

Diabetes ◽

10.2337/db19-1958-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 1958-P

Author(s):

THERESE S. SALAMEH ◽

WILLIAM MORTELL ◽

WILLIAM A. BANKS

Keyword(s):

Blood Brain Barrier ◽

Brain Barrier ◽

Barrier Dysfunction ◽

Blood Brain

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Role of Histaminergic System in Blood–Brain Barrier Dysfunction Associated with Neurological Disorders

Archives of Medical Research ◽

10.1016/j.arcmed.2014.11.010 ◽

2014 ◽

Vol 45 (8) ◽

pp. 677-686 ◽

Cited By ~ 17

Author(s):

Ivette Bañuelos-Cabrera ◽

María Guadalupe Valle-Dorado ◽

Blanca Irene Aldana ◽

Sandra Adela Orozco-Suárez ◽

Luisa Rocha

Keyword(s):

Blood Brain Barrier ◽

Neurological Disorders ◽

Brain Barrier ◽

Barrier Dysfunction ◽

Histaminergic System ◽

Blood Brain

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Alzheimer’s disease: A matter of blood–brain barrier dysfunction?

Journal of Experimental Medicine ◽

10.1084/jem.20171406 ◽

2017 ◽

Vol 214 (11) ◽

pp. 3151-3169 ◽

Cited By ~ 191

Author(s):

Axel Montagne ◽

Zhen Zhao ◽

Berislav V. Zlokovic

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Blood Brain Barrier ◽

Amyloid Β ◽

Brain Barrier ◽

Barrier Dysfunction ◽

Neurodegenerative Process ◽

Blood Brain ◽

Underlying Mechanisms

The blood–brain barrier (BBB) keeps neurotoxic plasma-derived components, cells, and pathogens out of the brain. An early BBB breakdown and/or dysfunction have been shown in Alzheimer’s disease (AD) before dementia, neurodegeneration and/or brain atrophy occur. However, the role of BBB breakdown in neurodegenerative disorders is still not fully understood. Here, we examine BBB breakdown in animal models frequently used to study the pathophysiology of AD, including transgenic mice expressing human amyloid-β precursor protein, presenilin 1, and tau mutations, and apolipoprotein E, the strongest genetic risk factor for AD. We discuss the role of BBB breakdown and dysfunction in neurodegenerative process, pitfalls in BBB measurements, and how targeting the BBB can influence the course of neurological disorder. Finally, we comment on future approaches and models to better define, at the cellular and molecular level, the underlying mechanisms between BBB breakdown and neurodegeneration as a basis for developing new therapies for BBB repair to control neurodegeneration.

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Role of NADPH Oxidase-Induced Hypoxia-Induced Factor-1α Increase in Blood-Brain Barrier Disruption after 2-Hour Focal Ischemic Stroke in Rat

Neural Plasticity ◽

10.1155/2021/9928232 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Yanping Wang ◽

Yufei Shen ◽

Xin Yu ◽

Jingxia Gu ◽

Xiaoling Zhang ◽

...

Keyword(s):

Ischemic Stroke ◽

Nadph Oxidase ◽

Acute Ischemic Stroke ◽

Blood Brain Barrier ◽

Critical Role ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Brain Barrier ◽

Blood Brain ◽

Junction Protein

We recently showed that inhibition of hypoxia-induced factor-1α (HIF-1α) decreased acute ischemic stroke-induced blood-brain barrier (BBB) damage. However, factors that induce the upregulation of HIF-1α expression remain unclear. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase played a critical role in reperfusion-induced BBB damage after stroke. However, the role of NADPH oxidase in BBB injury during the acute ischemia stage remains unclear. This study is aimed at investigating the role of NADPH oxidase in BBB injury and the expression of HIF-1α after acute ischemic stroke. A sutured middle cerebral artery occlusion (MCAO) model was used to mimic ischemic stroke in rats. Our results show that the inhibition of NADPH oxidase by apocynin can significantly reduce the BBB damage caused by 2 h ischemic stroke accompanied by reducing the degradation of tight junction protein occludin. In addition, treatment with apocynin significantly decreased the upregulation of HIF-1α induced by 2 h MCAO. More importantly, apocynin could also inhibit the MMP-2 upregulation. Of note, HIF-1α was not colocalized with a bigger blood vessel. Taken together, our results showed that inhibition of NADPH oxidase-mediated HIF-1α upregulation reduced BBB damage accompanied by downregulating MMP-2 expression and occludin degradation after 2 h ischemia stroke. These results explored the mechanism of BBB damage after acute ischemic stroke and may help reduce the associated cerebral hemorrhage transformation after thrombolysis and endovascular treatment after ischemic stroke.

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