scholarly journals Anti-high Mobility Group Box-1 Monoclonal Antibody Protects the Blood–Brain Barrier From Ischemia-Induced Disruption in Rats

Stroke ◽  
2011 ◽  
Vol 42 (5) ◽  
pp. 1420-1428 ◽  
Author(s):  
Jiyong Zhang ◽  
Hideo K. Takahashi ◽  
Keyue Liu ◽  
Hidenori Wake ◽  
Rui Liu ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Blood Brain Barrier ◽  
High Mobility ◽  
High Mobility Group ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Surgery Upregulates High Mobility Group Box-1 and Disrupts the Blood-Brain Barrier causing Cognitive Dysfunction in Aged Rats

2012 ◽  
Vol 18 (12) ◽  
pp. 994-1002 ◽  
Author(s):  
Hui-Juan He ◽  
Yi Wang ◽  
Yuan Le ◽  
Kai-Ming Duan ◽  
Xue-Bin Yan ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Blood Brain Barrier ◽  
High Mobility ◽  
High Mobility Group ◽  
Brain Barrier ◽  
Aged Rats ◽  
Blood Brain

scholarly journals High Mobility Group Box-1 and Blood–Brain Barrier Disruption

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2650
Author(s):  
Masahiro Nishibori ◽  
Dengli Wang ◽  
Daiki Ousaka ◽  
Hidenori Wake
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Brain Injuries ◽  
Inflammatory Responses ◽  
High Mobility ◽  
Brain Inflammation ◽  
High Mobility Group ◽  
Brain Barrier ◽  
Cns Diseases ◽  
Blood Brain

Increasing evidence suggests that inflammatory responses are involved in the progression of brain injuries induced by a diverse range of insults, including ischemia, hemorrhage, trauma, epilepsy, and degenerative diseases. During the processes of inflammation, disruption of the blood–brain barrier (BBB) may play a critical role in the enhancement of inflammatory responses and may initiate brain damage because the BBB constitutes an interface between the brain parenchyma and the bloodstream containing blood cells and plasma. The BBB has a distinct structure compared with those in peripheral tissues: it is composed of vascular endothelial cells with tight junctions, numerous pericytes surrounding endothelial cells, astrocytic endfeet, and a basement membrane structure. Under physiological conditions, the BBB should function as an important element in the neurovascular unit (NVU). High mobility group box-1 (HMGB1), a nonhistone nuclear protein, is ubiquitously expressed in almost all kinds of cells. HMGB1 plays important roles in the maintenance of chromatin structure, the regulation of transcription activity, and DNA repair in nuclei. On the other hand, HMGB1 is considered to be a representative damage-associated molecular pattern (DAMP) because it is translocated and released extracellularly from different types of brain cells, including neurons and glia, contributing to the pathophysiology of many diseases in the central nervous system (CNS). The regulation of HMGB1 release or the neutralization of extracellular HMGB1 produces beneficial effects on brain injuries induced by ischemia, hemorrhage, trauma, epilepsy, and Alzheimer’s amyloidpathy in animal models and is associated with improvement of the neurological symptoms. In the present review, we focus on the dynamics of HMGB1 translocation in different disease conditions in the CNS and discuss the functional roles of extracellular HMGB1 in BBB disruption and brain inflammation. There might be common as well as distinct inflammatory processes for each CNS disease. This review will provide novel insights toward an improved understanding of a common pathophysiological process of CNS diseases, namely, BBB disruption mediated by HMGB1. It is proposed that HMGB1 might be an excellent target for the treatment of CNS diseases with BBB disruption.

scholarly journals VX765 Attenuates Pyroptosis and HMGB1/TLR4/NF-κB Pathways to Improve Functional Outcomes in TBI Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-21 ◽  
Author(s):  
Zhezhe Sun ◽  
Mark Nyanzu ◽  
Su Yang ◽  
Xiaohong Zhu ◽  
Kankai Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Blood Brain Barrier ◽  
High Mobility ◽  
Brain Barrier ◽  
Neurological Deficits ◽  
Nf Kappa B ◽  
Neuroprotective Effects ◽  
Caspase 1 ◽  
Area Of Interest ◽  
Blood Brain

Background. Traumatic brain injury (TBI) refers to temporary or permanent damage to brain function caused by penetrating objects or blunt force trauma. TBI activates inflammasome-mediated pathways and other cell death pathways to remove inactive and damaged cells, however, they are also harmful to the central nervous system. The newly discovered cell death pattern termed pyroptosis has become an area of interest. It mainly relies on caspase-1-mediated pathways, leading to cell death. Methods. Our research focus is VX765, a known caspase-1 inhibitor which may offer neuroprotection after the process of TBI. We established a controlled cortical impact (CCI) mouse model and then controlled the degree of pyroptosis in TBI with VX765. The effects of caspase-1 inhibition on inflammatory response, pyroptosis, blood-brain barrier (BBB), apoptosis, and microglia activation, in addition to neurological deficits, were investigated. Results. We found that TBI led to NOD-like receptors (NLRs) as well as absent in melanoma 2 (AIM2) inflammasome-mediated pyroptosis in the damaged cerebral cortex. VX765 curbed the expressions of indispensable inflammatory subunits (caspase-1 as well as key downstream proinflammatory cytokines such as interleukin- (IL-) 1β and IL-18). It also inhibited gasdermin D (GSDMD) cleavage and apoptosis-associated spot-like protein (ASC) oligomerization in the injured cortex. In addition to the above, VX765 also inhibited the inflammatory activity of the high-mobility cassette -1/Toll-like receptor 4/nuclear factor-kappa B (HMGB1/TLR4/NF-kappa B) pathway. By inhibiting pyroptosis and inflammatory mediator expression, we demonstrated that VX765 can decrease blood-brain barrier (BBB) leakage, apoptosis, and microglia polarization to exhibit its neuroprotective effects. Conclusion. In conclusion, VX765 can counteract neurological damage after TBI by reducing pyroptosis and HMGB1/TLR4/NF-κB pathway activities. VX765 may have a good therapeutic effect on TBI.

scholarly journals Temporary disruption of the rat blood–brain barrier with a monoclonal antibody: A novel method for dynamic manganese-enhanced MRI

NeuroImage ◽  
2010 ◽  
Vol 50 (1) ◽  
pp. 7-14 ◽  
Author(s):  
Hanbing Lu ◽  
Steven Demny ◽  
Yantao Zuo ◽  
William Rea ◽  
Leiming Wang ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Rat Blood ◽  
Blood Brain ◽  
Enhanced Mri ◽  
Novel Method ◽  
Manganese Enhanced Mri

Osmotic Blood-Brain Barrier Modification: Monoclonal Antibody, Albumin, and Methotrexate Delivery to Cerebrospinal Fluid and Brain

Neurosurgery ◽  
1985 ◽  
Vol 17 (3) ◽  
pp. 419-423 ◽  
Author(s):  
Edward A. Neuwelt ◽  
Peggy A. Barnett ◽  
Christopher I. McCormick ◽  
Eugene P. Frenkel ◽  
John D. Minna
Keyword(s):  
Monoclonal Antibody ◽  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals High Mobility Group Protein 1 and Dickkopf-Related Protein 1 in Schizophrenia and Treatment-Resistant Schizophrenia: Associations with Interleukin-6, Symptom Domains, and Neurocognitive Impairments

2019 ◽  
Author(s):  
Arafat Hussein Al-Dujaili ◽  
Rana Fadhil Mousa ◽  
Hussein Kadhem Al-hakeim ◽  
Michael Maes
Keyword(s):  
Blood Brain Barrier ◽  
High Mobility ◽  
High Mobility Group ◽  
Brain Barrier ◽  
Beta Catenin ◽  
Related Protein ◽  
Treatment Resistant ◽  
High Mobility Group Protein ◽  
Neurotoxic Effects ◽  
Group Protein

Background: Schizophrenia and treatment-resistant schizophrenia (TRS) are associated with aberrations in immune-inflammatory pathways. Increased High Mobility Group Protein 1 (HMGB1), an inflammatory mediator, and Dickkopf-Related Protein (DKK1), a Wnt/β-catenin signaling antagonist, affect the blood-brain-barrier and induce neurotoxic effects and neurocognitive deficits.Aim of the study: The present study aims to examine HMGB1 and DDK1 in non-responders to treatments with antipsychotics (NRTT, n=60), partial RTT (PRTT, n=55) and healthy controls (n=43) in relation to established markers of schizophrenia including IL-6, IL-10 and CLL11 (eotaxin); and to delineate whether these proteins are associated with the schizophrenia symptom subdomains and neurocognitive impairments.Results: HMGB1, DKK1, IL-6 and CCL11 were significantly higher in schizophrenia patients than in controls. DKK1 and IL-6 were significantly higher in NRTT than in PRTT and controls while IL-10 was higher in NRTT than in controls. Binary logistic regression analysis showed that schizophrenia was best predicted by increased DDK1 and HMGB1 while NRTT (versus PRTT) was best predicted by increased IL-6 and CCL11 levels. A large part of the variance in psychosis, hostility, excitation, mannerism and negative (PHEMN) symptoms, and formal thought disorders was explained by HMGB1, IL-6, and CCL11 while most neurocognitive functions were predicted by HMGB1, DDK1 and CCL11. Conclusion: The neurotoxic effects of HMGB1, DKK1, IL-6 and CCL11 including effects on the blood-brain-barrier and the Wnt/β-catenin signaling pathway may cause impairments in executive functions, and working, episodic and semantic memory and explain, in part, PHEMN symptoms and a non-response to treatment with antipsychotic drugs.

scholarly journals Monoclonal Antibody-Glial-Derived Neurotrophic Factor Fusion Protein Penetrates the Blood-Brain Barrier in the Mouse

2010 ◽  
Vol 38 (4) ◽  
pp. 566-572 ◽  
Author(s):  
Qing-Hui Zhou ◽  
Ruben J. Boado ◽  
Jeff Zhiqiang Lu ◽  
Eric Ka-Wai Hui ◽  
William M. Pardridge
Keyword(s):  
Monoclonal Antibody ◽  
Fusion Protein ◽  
Blood Brain Barrier ◽  
Neurotrophic Factor ◽  
Brain Barrier ◽  
Blood Brain ◽  
Glial Derived Neurotrophic Factor
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