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 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 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 Severe Hypoglycemia Contributing to Cognitive Dysfunction in Diabetic Mice is Associated with Pericyte and Blood–Brain Barrier Dysfunction

2021 ◽  
Author(s):  
Lu Lin ◽  
Lishan Huang ◽  
Lijing Wang ◽  
Yubin Wu ◽  
Zhou Chen ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Cognitive Dysfunction ◽  
Blood Brain Barrier ◽  
Severe Hypoglycemia ◽  
Brain Barrier ◽  
Blue Staining ◽  
Diabetic Patients ◽  
Inflammatory Factor ◽  
Diabetic Mice ◽  
Blood Brain

Abstract Background: Severe hypoglycemia can cause cognitive impairment in diabetic patients, but the underlying molecular mechanism remains unclear.Objective: To assess the effect of severe hypoglycemia on cognitive function in diabetic mice to clarify the relationship between the mechanism and dysfunction of pericytes and the blood–brain barrier (BBB).Method: We established type 1 diabetes mellitus in 80 male C57BL/6J mice by intraperitoneal injection of streptozotocin (180 mg/kg). Further abdominal injection of short-acting insulin induced severe hypoglycemia. The mice were divided into normal, diabetes, and diabetic + severe hypoglycemia groups, and their blood glucose and general weight index were examined. Pericyte and BBB morphology and function were detected by histological and western blot analyses, BBB permeability was detected by Evans blue staining, and cognitive function was detected with the Morris water maze.Results: Severe hypoglycemia aggravated the histological damage, BBB damage, brain edema, and pericyte loss in the diabetic mice. It also reduced the expression of the BBB tight junction proteins occludin and claudin-5, the expression of the pericyte-specific markers PDGFR-β (platelet-derived growth factor receptor-β) and α-SMA, and increased the expression of the inflammatory factor MMP9. At the same time, diabetic mice with severe hypoglycemia had significantly reduced cognitive function.Conclusion: Severe hypoglycemia leads to cognitive dysfunction in diabetic mice, and its possible mechanism is related to pericyte dysfunction and BBB destruction.

Ulinastatin decreases permeability of blood--brain barrier by inhibiting expression of MMP-9 and t-PA in postoperative aged rats

2015 ◽  
Vol 126 (5) ◽  
pp. 463-468 ◽  
Author(s):  
Li Ma ◽  
Hui Zhang ◽  
Yong-zhe Liu ◽  
Yan-ling Yin ◽  
Ya-qun Ma ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Aged Rats ◽  
Blood Brain
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