scholarly journals Oxidative Stress Increases Blood–Brain Barrier Permeability and Induces Alterations in Occludin during Hypoxia–Reoxygenation

2010 ◽  
Vol 30 (9) ◽  
pp. 1625-1636 ◽  
Author(s):  
Jeffrey J Lochhead ◽  
Gwen McCaffrey ◽  
Colleen E Quigley ◽  
Jessica Finch ◽  
Kristin M DeMarco ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Brain Barrier ◽  
Critical Role ◽  
Brain Barrier ◽  
Central Component ◽  
Radical Scavenger ◽  
Cerebral Microvessels ◽  
Disease States ◽  
Blood Brain ◽  
The Brain

The blood–brain barrier (BBB) has a critical role in central nervous system homeostasis. Intercellular tight junction (TJ) protein complexes of the brain microvasculature limit paracellular diffusion of substances from the blood into the brain. Hypoxia and reoxygenation (HR) is a central component to numerous disease states and pathologic conditions. We have previously shown that HR can influence the permeability of the BBB as well as the critical TJ protein occludin. During HR, free radicals are produced, which may lead to oxidative stress. Using the free radical scavenger tempol (200 mg/kg, intraperitoneal), we show that oxidative stress produced during HR (6% O2 for 1 h, followed by room air for 20 min) mediates an increase in BBB permeability in vivo using in situ brain perfusion. We also show that these changes are associated with alterations in the structure and localization of occludin. Our data indicate that oxidative stress is associated with movement of occludin away from the TJ. Furthermore, subcellular fractionation of cerebral microvessels reveals alterations in occludin oligomeric assemblies in TJ associated with plasma membrane lipid rafts. Our data suggest that pharmacological inhibition of disease states with an HR component may help preserve BBB functional integrity.

scholarly journals The Potential Roles of Blood–Brain Barrier and Blood–Cerebrospinal Fluid Barrier in Maintaining Brain Manganese Homeostasis

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1833
Author(s):  
Shannon Morgan McCabe ◽  
Ningning Zhao
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Blood Circulation ◽  
Critical Role ◽  
Systemic Circulation ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Brain

Manganese (Mn) is a trace nutrient necessary for life but becomes neurotoxic at high concentrations in the brain. The brain is a “privileged” organ that is separated from systemic blood circulation mainly by two barriers. Endothelial cells within the brain form tight junctions and act as the blood–brain barrier (BBB), which physically separates circulating blood from the brain parenchyma. Between the blood and the cerebrospinal fluid (CSF) is the choroid plexus (CP), which is a tissue that acts as the blood–CSF barrier (BCB). Pharmaceuticals, proteins, and metals in the systemic circulation are unable to reach the brain and spinal cord unless transported through either of the two brain barriers. The BBB and the BCB consist of tightly connected cells that fulfill the critical role of neuroprotection and control the exchange of materials between the brain environment and blood circulation. Many recent publications provide insights into Mn transport in vivo or in cell models. In this review, we will focus on the current research regarding Mn metabolism in the brain and discuss the potential roles of the BBB and BCB in maintaining brain Mn homeostasis.

Abstract TP340: The Level of Occludin in Blood as a Potential Biomarker for Blood-Brain Barrier Damage and Predicting Hemorrhage Transformation After Acute Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Zhifeng Qi ◽  
Ke Jian Liu
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Brain Infarction ◽  
Critical Role ◽  
Onset Time ◽  
Brain Barrier ◽  
Cerebral Microvessels ◽  
Blood Brain ◽  
Potential Biomarker

Fear of hemorrhage transformation (HT) has been the primary reason for withholding the effective recanalization therapies (thrombolysis or thrombectomy) from most acute ischemic stroke (AIS) patients. Currently there is no reliable indicator available to predict HT before recanalization. The degradation of tight junction proteins plays a critical role in blood-brain barrier (BBB) disruption in ischemic stroke. We hypothesize that since occludin fragment in peripheral blood is derived from the degradation of occludin on cerebral microvessels, elevated blood occludin level directly reflects BBB disruption and may serve as a biomarker for BBB damage to predict the risk of HT after recanalization. In this study, we determined occludin fragment in the blood of rats, non-human primates and human patients after AIS using ELISA assay, and evaluated its level with BBB damage, HT, and other neurological outcomes. We found that ischemia induced rapid occludin degradation and BBB disruption, while occludin fragment was released into the blood circulation. Cerebral ischemia resulted in a dramatic increase of occludin fragments in rat blood samples after 4-hr ischemia, which was correlated well with occludin loss from ischemic cerebral microvessels. In the blood sample from ischemic rhesus monkeys, occludin level significantly increased after 2h ischemia from baseline, which correlated well with brain infarction shown in MRI images. We further collected the sera of AIS patients as early as they arrived at hospital. Our results indicated that the level of occludin increased in accord with ischemia onset time and neurological dysfunctions. The level of blood occludin in AIS patients with HT was much higher that those without HT. Together, our findings from rats, non-human primates and patients suggest that the level of occludin fragment in blood could serve as a biomarker for HT and neurological outcome following AIS, which could be used to safely guide recanalization for AIS in the clinic.

Oatp58Dc contributes to blood-brain barrier function by excluding organic anions from the Drosophila brain

2013 ◽  
Vol 305 (5) ◽  
pp. C558-C567 ◽  
Author(s):  
Sara Seabrooke ◽  
Michael J. O'Donnell
Keyword(s):  
Blood Brain Barrier ◽  
Organic Anion ◽  
Complex Structure ◽  
Critical Role ◽  
Organic Anions ◽  
Molecular Techniques ◽  
Brain Barrier ◽  
Blood Brain ◽  
Wide Range ◽  
The Brain

The blood-brain barrier (BBB) physiologically isolates the brain from the blood and, thus, plays a vital role in brain homeostasis. Ion transporters play a critical role in this process by effectively regulating access of chemicals to the brain. Organic anion-transporting polypeptides (Oatps) transport a wide range of amphipathic substrates and are involved in efflux of chemicals across the vertebrate BBB. The anatomic complexity of the vascularized vertebrate BBB, however, creates challenges for experimental analysis of these processes. The less complex structure of the Drosophila BBB facilitates measurement of solute transport. Here we investigate a physiological function for Oatp58Dc in transporting small organic anions across the BBB. We used genetic manipulation, immunocytochemistry, and molecular techniques to supplement a whole animal approach to study the BBB. For this whole animal approach, the traceable small organic anion fluorescein was injected into the hemolymph. This research shows that Oatp58Dc is involved in maintaining a chemical barrier against fluorescein permeation into the brain. Oatp58Dc expression was found in the perineurial and subperineurial glia, as well as in postmitotic neurons. We specifically targeted knockdown of Oatp58Dc expression in the perineurial and subperineurial glia to reveal that Oatp58Dc expression in the perineurial glia is necessary to maintain the barrier against fluorescein influx into the brain. Our results show that Oatp58Dc contributes to maintenance of a functional barrier against fluorescein influx past the BBB into the brain.

Evaluation of the effect of stress on the blood–brain barrier: critical role of the brain perfusion time

2001 ◽  
Vol 905 (1-2) ◽  
pp. 21-25 ◽  
Author(s):  
Haim Ovadia ◽  
Oded Abramsky ◽  
Shaul Feldman ◽  
Joseph Weidenfeld
Keyword(s):  
Blood Brain Barrier ◽  
Critical Role ◽  
Brain Perfusion ◽  
Brain Barrier ◽  
Blood Brain ◽  
Perfusion Time ◽  
The Brain

scholarly journals Disruption in the Blood-Brain Barrier: The Missing Link between Brain and Body Inflammation in Bipolar Disorder?

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Jay P. Patel ◽  
Benicio N. Frey
Keyword(s):  
Bipolar Disorder ◽  
Blood Brain Barrier ◽  
Peripheral Blood ◽  
Critical Role ◽  
Brain Barrier ◽  
Inflammatory Conditions ◽  
Blood Brain ◽  
The Central Nervous System ◽  
The Brain

The blood-brain barrier (BBB) regulates the transport of micro- and macromolecules between the peripheral blood and the central nervous system (CNS) in order to maintain optimal levels of essential nutrients and neurotransmitters in the brain. In addition, the BBB plays a critical role protecting the CNS against neurotoxins. There has been growing evidence that BBB disruption is associated with brain inflammatory conditions such as Alzheimer’s disease and multiple sclerosis. Considering the increasing role of inflammation and oxidative stress in the pathophysiology of bipolar disorder (BD), here we propose a novel model wherein transient or persistent disruption of BBB integrity is associated with decreased CNS protection and increased permeability of proinflammatory (e.g., cytokines, reactive oxygen species) substances from the peripheral blood into the brain. These events would trigger the activation of microglial cells and promote localized damage to oligodendrocytes and the myelin sheath, ultimately compromising myelination and the integrity of neural circuits. The potential implications for research in this area and directions for future studies are discussed.

scholarly journals A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Hossam Kadry ◽  
Behnam Noorani ◽  
Luca Cucullo
Keyword(s):  
Blood Brain Barrier ◽  
Structural Integrity ◽  
Critical Role ◽  
Brain Barrier ◽  
Clinical Aspects ◽  
Advantages And Disadvantages ◽  
Blood Brain ◽  
The Brain

AbstractThe blood–brain barrier is playing a critical role in controlling the influx and efflux of biological substances essential for the brain’s metabolic activity as well as neuronal function. Thus, the functional and structural integrity of the BBB is pivotal to maintain the homeostasis of the brain microenvironment. The different cells and structures contributing to developing this barrier are summarized along with the different functions that BBB plays at the brain–blood interface. We also explained the role of shear stress in maintaining BBB integrity. Furthermore, we elaborated on the clinical aspects that correlate between BBB disruption and different neurological and pathological conditions. Finally, we discussed several biomarkers that can help to assess the BBB permeability and integrity in-vitro or in-vivo and briefly explain their advantages and disadvantages.

scholarly journals Brain Barriers and brain fluids research in 2020 and the fluids and barriers of the CNS thematic series on advances in in vitro modeling of the blood–brain barrier and neurovascular unit

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Richard F. Keep ◽  
Hazel C. Jones ◽  
Lester R. Drewes
Keyword(s):  
Blood Brain Barrier ◽  
Neurovascular Unit ◽  
Brain Barrier ◽  
In Vitro Modeling ◽  
Disease States ◽  
System Disease ◽  
Blood Brain ◽  
The Brain ◽  
Brain Barriers

AbstractThis editorial discusses advances in brain barrier and brain fluid research in 2020. Topics include: the cerebral endothelium and the neurovascular unit; the choroid plexus; the meninges; cerebrospinal fluid and the glymphatic system; disease states impacting the brain barriers and brain fluids; drug delivery to the brain. This editorial also highlights the recently completed Fluids Barriers CNS thematic series entitled, ‘Advances in in vitro modeling of the blood–brain barrier and neurovascular unit’. Such in vitro modeling is progressing rapidly.

Mechanism of Fisetin Inhibiting Oxidative Stress to Alleviate the Damage of Blood Brain Barrier, Around the Intracerebral Hemorrhag Lesions

2020 ◽  
Vol 10 (6) ◽  
pp. 862-867
Author(s):  
Xinbo Ge ◽  
Qunfu Yang ◽  
Zhenbo Liu ◽  
Tao Zhang ◽  
Chao Liang
Keyword(s):  
Oxidative Stress ◽  
Water Content ◽  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Stress Index ◽  
Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
The Brain

Background: The paper determined the brain water content, blood-brain barrier permeability, oxidative stress-related indicators, expressions of tight junction-associated proteins ZO-1 and Occludin, as well as expressions of ERK, p38, and JNK proteins in cerebral hemorrhage rats. The paper explored whether Fisetin reduced the damage of blood-brain barrier caused by cerebral hemorrhage through inhibiting oxidative stress, and investigated whether MAPK pathway is the main pathway for BBB damage caused by oxidative stress. Material and Methods: Rat ICH model was established. After 72 hours, mNSS score was used to measure the behavior of rats. The water content of brain tissue was determined by dry-wet weight method. Evans blue method was applied to measure the blood-brain barrier permeability. Oxidative stress index was detected by spectrophotometer. The expressions of ZO-1, Occludin, ERK, p38 and JNK proteins in rat brain tissue were determined by Western blot. Results: Fisetin significantly reduced the mNSS score, brain water content, bloodbrain barrier permeability, oxidative stress index and the expressions of ERK, p38 and JNK in rat ICH model, and also significantly increased the antioxidant index of rat ICH model, as well as the expressions of ZO-1 and Occludin. The effect is becoming more significant as the therapeutic dose is increased. Conclusion: Fisetin can inhibit the oxidative stress and alleviate the damage of BBB around the lesions of rat ICH model, thus alleviating secondary brain injury. In the rat ICH model, the expressions of ERK, p38 and JNK in the brain tissue around the lesion are increased and oxidized. The stress response is enhanced, and Fisetin inhibits oxidative stress and the expressions of ERK, p38, and JNK. MAPK is imperative in the process of oxidative stress-induced BBB damage in rat ICH model.

scholarly journals Glioblastoma Chemoresistance: The Double Play by Microenvironment and Blood-Brain Barrier

2018 ◽  
Vol 19 (10) ◽  
pp. 2879 ◽  
Author(s):  
Martina Da Ros ◽  
Veronica De Gregorio ◽  
Anna Iorio ◽  
Laura Giunti ◽  
Milena Guidi ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Immune Escape ◽  
Critical Role ◽  
Brain Barrier ◽  
Multi Drug Resistance ◽  
Blood Brain ◽  
Checkpoint Inhibitor Therapy ◽  
Drug Resistant Phenotype ◽  
And Behavior ◽  
The Brain

For glioblastoma, the tumor microenvironment (TME) is pivotal to support tumor progression and therapeutic resistance. TME consists of several types of stromal, endothelial and immune cells, which are recruited by cancer stem cells (CSCs) to influence CSC phenotype and behavior. TME also promotes the establishment of specific conditions such as hypoxia and acidosis, which play a critical role in glioblastoma chemoresistance, interfering with angiogenesis, apoptosis, DNA repair, oxidative stress, immune escape, expression and activity of multi-drug resistance (MDR)-related genes. Finally, the blood brain barrier (BBB), which insulates the brain microenvironment from the blood, is strongly linked to the drug-resistant phenotype of glioblastoma, being a major physical and physiological hurdle for the delivery of chemotherapy agents into the brain. Here, we review the features of the glioblastoma microenvironment, focusing on their involvement in the phenomenon of chemoresistance; we also summarize recent advances in generating systems to modulate or bypass the BBB for drug delivery into the brain. Genetic aspects associated with glioblastoma chemoresistance and current immune-based strategies, such as checkpoint inhibitor therapy, are described too.

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