scholarly journals Acute Methylglyoxal-Induced Damage In Blood-Brain Barrier And Hippocampal Tissue

2021 ◽  
Author(s):  
Lílian Juliana Lissner ◽  
Krista Minéia Wartchow ◽  
Leticia Rodrigues ◽  
Larissa Daniele Bobermin ◽  
Ederson Borba ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Connexin 43 ◽  
Short Interval ◽  
Antioxidant Response ◽  
Treated Group ◽  
High Reactivity ◽  
Brain Barrier ◽  
Glucose Levels ◽  
Blood Brain ◽  
Hippocampal Tissue

Abstract Methylglyoxal (MG) is a reactive dicarbonyl compound formed mostly by the glycolytic pathway. Elevated blood glucose levels can cause MG accumulation in plasma and cerebrospinal fluid diabetes mellitus and Alzheimer’s disease, where the high reactivity of MG leads to modification of proteins and other biomolecules, generating advanced glycation end products (AGEs) appointed as mediators in those neurodegenerative diseases. Herein, we investigated the blood-brain barrier (BBB) integrity and astrocyte response in the hippocampus to acute insult induced by MG, administered ICV in rats. Seventy-two hours later, a loss of BBB integrity was observed, as assessed by the entry of Evans dye into brain tissue and albumin in the CSF, as well as a decrease of aquaporin-4 and connexin-43 in hippocampal tissue. MG did not induce changes in hippocampal contents of RAGE in this short interval, but decreased the expression of S100B, an astrocyte secreted protein that binds RAGE. The expressions of two important transcription factors of antioxidant response - NfkB and Nrf2, were not changed. However, hemeoxigenase-1 was upregulated in MG-treated group. This data corroborates with the idea that astrocytes, the main cells responsible for MG clearance, are targets of MG toxicity and that BBB dysfunction induced by this compound may contribute to behavioral and cognitive alterations observed in these animals.

Are Synchronized Changes in Connexin-43 and Caveolin-3 a Bystander Effect in a Phoneutria nigriventer Venom Model of Blood-Brain Barrier Breakdown?

2016 ◽  
Vol 59 (4) ◽  
pp. 452-463 ◽  
Author(s):  
Edilene Siqueira Soares ◽  
Monique Culturato Padilha Mendonça ◽  
Thalita Rocha ◽  
Evanguedes Kalapothakis ◽  
Maria Alice da Cruz-Höfling
Keyword(s):  
Blood Brain Barrier ◽  
Connexin 43 ◽  
Bystander Effect ◽  
Brain Barrier ◽  
Blood Brain ◽  
Barrier Breakdown ◽  
Blood Brain Barrier Breakdown ◽  
Phoneutria Nigriventer

scholarly journals Behind Brain Metastases Formation: Cellular and Molecular Alterations and Blood–Brain Barrier Disruption

2021 ◽  
Vol 22 (13) ◽  
pp. 7057
Author(s):  
Joana Godinho-Pereira ◽  
Ana Rita Garcia ◽  
Inês Figueira ◽  
Rui Malhó ◽  
Maria Alexandra Brito
Keyword(s):  
Endothelial Cells ◽  
Brain Metastases ◽  
Blood Brain Barrier ◽  
Light Chain ◽  
Connexin 43 ◽  
Myosin Light Chain ◽  
Brain Barrier ◽  
Malignant Cells ◽  
Blood Brain ◽  
Junction Protein

Breast cancer (BC) brain metastases is a life-threatening condition to which accounts the poor understanding of BC cells’ (BCCs) extravasation into the brain, precluding the development of preventive strategies. Thus, we aimed to unravel the players involved in the interaction between BCCs and blood–brain barrier (BBB) endothelial cells underlying BBB alterations and the transendothelial migration of malignant cells. We used brain microvascular endothelial cells (BMECs) as a BBB in vitro model, under conditions mimicking shear stress to improve in vivo-like BBB features. Mixed cultures were performed by the addition of fluorescently labelled BCCs to distinguish individual cell populations. BCC–BMEC interaction compromised BBB integrity, as revealed by junctional proteins (β-catenin and zonula occludens-1) disruption and caveolae (caveolin-1) increase, reflecting paracellular and transcellular hyperpermeability, respectively. Both BMECs and BCCs presented alterations in the expression pattern of connexin 43, suggesting the involvement of the gap junction protein. Myosin light chain kinase and phosphorylated myosin light chain were upregulated, revealing the involvement of the endothelial cytoskeleton in the extravasation process. β4-Integrin and focal adhesion kinase were colocalised in malignant cells, reflecting molecular interaction. Moreover, BCCs exhibited invadopodia, attesting migratory properties. Collectively, hub players involved in BC brain metastases formation were unveiled, disclosing possible therapeutic targets for metastases prevention.

scholarly journals Reorganization of Gap Junctions after Focused Ultrasound Blood–Brain Barrier Opening in the Rat Brain

2010 ◽  
Vol 30 (7) ◽  
pp. 1394-1402 ◽  
Author(s):  
Angelika Alonso ◽  
Eileen Reinz ◽  
Jürgen W Jenne ◽  
Marc Fatar ◽  
Hannah Schmidt-Glenewinkel ◽  
...  
Keyword(s):  
Gap Junctions ◽  
Blood Brain Barrier ◽  
Cellular Response ◽  
Connexin 43 ◽  
Brain Barrier ◽  
Ultrasound Exposure ◽  
Connexin 36 ◽  
Blood Brain ◽  
Gap Junctional ◽  
Bbb Opening

Ultrasound-induced opening of the blood–brain barrier (BBB) is an emerging technique for targeted drug delivery to the central nervous system. Gap junctions allow transfer of information between adjacent cells and are responsible for tissue homeostasis. We examined the effect of ultrasound-induced BBB opening on the structure of gap junctions in cortical neurons, expressing Connexin 36, and astrocytes, expressing Connexin 43, after focused 1-MHz ultrasound exposure at 1.25 MPa of one hemisphere together with intravenous microbubble (Optison, Oslo, Norway) application. Quantification of immunofluorescence signals revealed that, compared with noninsonicated hemispheres, small-sized Connexin 43 and 36 gap-junctional plaques were markedly reduced in areas with BBB breakdown after 3 to 6 hours (34.02±6.04% versus 66.49±2.16%, P=0.02 for Connexin 43; 33.80±1.24% versus 36.77±3.43%, P=0.07 for Connexin 36). Complementing this finding, we found significant increases in large-sized gap-junctional plaques (5.76±0.96% versus 1.02±0.84%, P=0.05 for Connexin 43; 5.62±0.22% versus 4.65±0.80%, P=0.02 for Connexin 36). This effect was reversible at 24 hours after ultrasound exposure. Western blot analyses did not show any change in the total connexin amount. These results indicate that ultrasound-induced BBB opening leads to a reorganization of gap-junctional plaques in both neurons and astrocytes. The plaque-size increase may be a cellular response to imbalances in extracellular homeostasis after BBB leakage.

scholarly journals The neurotoxicity induced by PM2.5 might be strongly related to changes of the hippocampal tissue structure and neurotransmitter levels

2018 ◽  
Vol 7 (6) ◽  
pp. 1144-1152 ◽  
Author(s):  
Qingzhao Li ◽  
Jiali Zheng ◽  
Sheng Xu ◽  
Jingshu Zhang ◽  
Yanhua Cao ◽  
...  
Keyword(s):  
Nervous System ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Tissue Structure ◽  
Metal Elements ◽  
Blood Brain ◽  
Hippocampal Tissue ◽  
Complex Components

Objective: The complex components of PM2.5 including metal elements transported through the blood brain barrier could induce nervous system damage.

Protective Effects of Ginsenoside Rb1 against Blood–Brain Barrier Damage Induced by Human Immunodeficiency Virus-1 Tat Protein and Methamphetamine in Sprague-Dawley Rats

2018 ◽  
Vol 46 (03) ◽  
pp. 551-566 ◽  
Author(s):  
Juan Li ◽  
Bairui Zeng ◽  
Xiao Hu ◽  
Zhen Li ◽  
Dongxian Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Brain Barrier ◽  
Treated Group ◽  
Neurocognitive Disorders ◽  
Brain Barrier ◽  
Tat Protein ◽  
Sprague Dawley ◽  
Related Factors ◽  
Blood Brain ◽  
Hiv 1

Although antiretroviral therapy has helped to improve the lives of individuals infected with human immunodeficiency virus 1 (HIV-1), these patients are often still afflicted with HIV-1-associated neurocognitive disorders, which can lead to neurocognitive impairment and even dementia, and continue to hamper their quality of life. Methamphetamine abuse in HIV-1 patients poses a potential risk for HIV-associated neurocognitive disorders, because methamphetamine and HIV-1 proteins such as transactivator of transcription can synergistically damage the blood–brain barrier (BBB). In this study, we aimed to examine the effects of methamphetamine and HIV-1 Tat protein on the blood–brain barrier function and to determine whether ginsenoside Rb1 (GsRb1) plays a role in protecting the BBB. Sprague-Dawley rats were divided into four groups. The experimental groups received methamphetamine and HIV-1 Tat protein or both and the control group received saline or GsRb1 pretreatment. Oxidative stress-related factors, tight junction (TJ) proteins, blood–brain barrier permeability, and morphological changes were recorded in each group. The results showed that the group treated with Methamphetamine[Formula: see text]Tat showed a significant change at the ultrastructural level and in the levels of oxidative stress-related factors, TJ proteins, and BBB permeability, suggesting that the BBB function was severely damaged by HIV-1 Tat and methamphetamine synergistically. However, malondialdehyde levels and BBB permeability were lower and the oxidative stress-related factors superoxide dismutase and glutathione were higher in the GsRb1-treated group than in the Methamphetamine[Formula: see text]Tat-treated group, indicating that GsRb1 can protect the BBB against the toxic effects of HIV-1 Tat and methamphetamine. These results show that GsRb1 may offer a potential therapeutic option for patients with HIV-associated neurocognitive disorders or other neurodegenerative diseases.

Polarized hemichannel opening of pannexin 1/connexin 43 contributes to dysregulation of transport function in blood-brain barrier endothelial cells

2020 ◽  
Vol 132 ◽  
pp. 104600 ◽  
Author(s):  
Masanori Tachikawa ◽  
Koji Murakami ◽  
Ryo Akaogi ◽  
Shin-ichi Akanuma ◽  
Tetsuya Terasaki ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Connexin 43 ◽  
Brain Barrier ◽  
Transport Function ◽  
Pannexin 1 ◽  
Blood Brain
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