A Polyphenolic Complex Attenuates Inflammatory Response and Blood- Brain Barrier Disruption

2020 ◽  
Vol 17 (3) ◽  
pp. 286-293 ◽  
Author(s):  
Yuting Bian ◽  
Toru Yamashita ◽  
Yuki Taira ◽  
Jingwei Shang ◽  
Keiichiro Tsunoda ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Blood Brain Barrier ◽  
Rosmarinic Acid ◽  
Infarct Volume ◽  
Brain Barrier ◽  
Total Phenolic ◽  
Necrosis Factor Alpha ◽  
Monocyte Chemoattractant Protein 1 ◽  
Blood Brain ◽  
Anti Inflammatory

Background: Cerebral ischemia causes a strong inflammatory response. Neumentix is a dietary supplement containing 14.9% rosmarinic acid and 29.9% total phenolic content, which has been proved to be beneficial against inflammatory response. Therefore, Neumentix’s effect on anti-inflammatory and blood brain barrier (BBB) disruption in transient middle cerebral artery occlusion (tMCAO) model mice is investigated in this study. Methods: After the pretreatment of vehicle or Neumentix 134 mg/kg/d, intraperitoneal injection (i.p.) (containing rosmarinic acid 20 mg/kg/d) for 14 days, mice were subjected to tMCAO for 60 min and kept receiving vehicle or Neumentix daily 5 days afterward. Results: Neumentix treatment ameliorated neurobehavioral impairment in the corner test (5d after tMCAO, **P<0.01), reduced infarct volume (#P<0.05), suppressed expression of ionized calciumbinding adapter molecule-1 (Iba-1), tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) (###P<0.001), and improved the integrity of BBB (§P<0.05) at 5 days after tMCAO. Conclusios: The present study provided an evidence of Neumentix’s anti-inflammatory and neuroprotection effect against BBB disruption on experimental tMCAO model mice, suggesting that Neumentix could be a potential therapeutic agent for stroke.

Combined Ischemic Preconditioning and Resveratrol Improved Bloodbrain Barrier Breakdown via Hippo/YAP/TAZ Signaling Pathway

2020 ◽  
Vol 18 (9) ◽  
pp. 713-722 ◽  
Author(s):  
Ganji Hong ◽  
Ying Yan ◽  
Yali Zhong ◽  
Jianer Chen ◽  
Fei Tong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Blood Brain Barrier ◽  
Ischemic Preconditioning ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Cerebral Infarct ◽  
Brain Barrier ◽  
Binding Motif ◽  
Blood Brain ◽  
Barrier Breakdown

Background: Transient Ischemia/Reperfusion (I/R) is the main reason for brain injury and results in disruption of the Blood-Brain Barrier (BBB). It had been reported that BBB injury is one of the main risk factors for early death in patients with cerebral ischemia. Numerous investigations focus on the study of BBB injury which have been carried out. Objective: The objective of this study was to investigate the treatment function of the activation of the Hippo/Yes-Associated Protein (YAP) signaling pathway by combined Ischemic Preconditioning (IPC) and resveratrol (RES) before brain Ischemia/Reperfusion (BI/R) improves Blood-Brain Barrier (BBB) disruption in rats. Methods: Sprague-Dawley (SD) rats were pretreated with 20 mg/kg RES and IPC and then subjected to 2 h of ischemia and 22 h of reperfusion. The cerebral tissues were collected; the cerebral infarct volume was determined; the Evans Blue (EB) level, the brain Water Content (BWC), and apoptosis were assessed; and the expressions of YAP and TAZ were investigated in cerebral tissues. Results: Both IPC and RES preconditioning reduced the cerebral infarct size, improved BBB permeability, lessened apoptosis, and upregulated expressions of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) compared to the Ischemia/Reperfusion (I/R) group, while combined IPC and RES significantly enhanced this action. Conclusion: combined ischemic preconditioning and resveratrol improved blood-brain barrier breakdown via Hippo/YAP/TAZ signaling pathway.

scholarly journals Could Lipoxins Represent a New Standard in Ischemic Stroke Treatment?

2021 ◽  
Vol 22 (8) ◽  
pp. 4207
Author(s):  
Nikola Tułowiecka ◽  
Dariusz Kotlęga ◽  
Andrzej Bohatyrewicz ◽  
Małgorzata Szczuko
Keyword(s):  
Ischemic Stroke ◽  
Cardiovascular Diseases ◽  
Blood Brain Barrier ◽  
Inflammatory Cytokines ◽  
The Body ◽  
Brain Barrier ◽  
Lipoxin A4 ◽  
Stroke Treatment ◽  
Blood Brain ◽  
Anti Inflammatory

Introduction: Cardiovascular diseases including stroke are one of the most common causes of death. Their main cause is atherosclerosis and chronic inflammation in the body. An ischemic stroke may occur as a result of the rupture of unstable atherosclerotic plaque. Cardiovascular diseases are associated with uncontrolled inflammation. The inflammatory reaction produces chemical mediators that stimulate the resolution of inflammation. One of these mediators is lipoxins—pro-resolving mediators that are derived from the omega-6 fatty acid family, promoting inflammation relief and supporting tissue regeneration. Aim: The aim of the study was to review the available literature on the therapeutic potential of lipoxins in the context of ischemic stroke. Material and Methods: Articles published up to 31 January 2021 were included in the review. The literature was searched on the basis of PubMed and Embase in terms of the entries: ‘stroke and lipoxin’ and ‘stroke and atherosclerosis’, resulting in over 110 articles in total. Studies that were not in full-text English, letters to the editor, and conference abstracts were excluded. Results: In animal studies, the injection/administration of lipoxin A4 improved the integrity of the blood–brain barrier (BBB), decreased the volume of damage caused by ischemic stroke, and decreased brain edema. In addition, lipoxin A4 inhibited the infiltration of neutrophils and the production of cytokines and pro-inflammatory chemokines, such as interleukin (Il-1β, Il-6, Il-8) and tumor necrosis factor-α (TNF-α). The beneficial effects were also observed after introducing the administration of lipoxin A4 analog—BML-111. BML-111 significantly reduces the size of a stroke and protects the cerebral cortex, possibly by reducing the permeability of the blood–brain barrier. Moreover, more potent than lipoxin A4, it has an anti-inflammatory effect by inhibiting the production of pro-inflammatory cytokines and increasing the amount of anti-inflammatory cytokines. Conclusions: Lipoxins and their analogues may find application in reducing damage caused by stroke and improving the prognosis of patients after ischemic stroke.

Comparative changes in the blood-brain barrier and cerebral infarction of SHR and WKY rats

2007 ◽  
Vol 292 (5) ◽  
pp. R1881-R1892 ◽  
Author(s):  
Sharon Hom ◽  
Melissa A. Fleegal ◽  
Richard D. Egleton ◽  
Christopher R. Campos ◽  
Brian T. Hawkins ◽  
...  
Keyword(s):  
Cerebral Infarction ◽  
Blood Brain Barrier ◽  
Infarct Volume ◽  
Brain Barrier ◽  
Ion Transporter ◽  
Transporter Proteins ◽  
Wky Rats ◽  
Blood Brain ◽  
Hypertension Development ◽  
The Brain

Hypertension is involved in the exacerbation of stroke. It is unclear how blood-brain barrier (BBB) tight-junction (TJ) and ion transporter proteins critical for maintaining brain homeostasis contribute to cerebral infarction during hypertension development. In the present study, we investigated cerebral infarct volume following permanent 4-h middle cerebral artery occlusion (MCAO) and characterized the expression of BBB TJ and ion transporter proteins in brain microvessels of spontaneously hypertensive rats (SHR) compared with age-matched Wistar-Kyoto (WKY) rats at 5 wk (prehypertension), 10 wk (early-stage hypertension), and 15 wk (later-stage hypertension) of age. Hypertensive SHR show increased infarct volume following MCAO compared with WKY control rats. BBB TJ and ion transporter proteins, known to contribute to edema and fluid volume changes in the brain, show differential protein expression patterns during hypertension development. Western blot analysis of TJ protein zonula occludens-2 (ZO-2) showed decreased expression, while ion transporter, Na+/H+ exchanger 1 (NHE-1), was markedly increased in hypertensive SHR. Expression of TJ proteins ZO-1, occludin, actin, claudin-5, and Na+-K+-2Cl− cotransporter remain unaffected in SHR compared with control. Selective inhibition of NHE-1 using dimethylamiloride significantly attenuated ischemia-induced infarct volume in hypertensive SHR following MCAO, suggesting a novel role for NHE-1 in the brain in the regulation of ischemia-induced infarct volume in SHR.

Abstract TP80: Panaxatriol Saponins Attenuates Blood-brain Barrier Disruption and Promotes Angiogenesis After Ischemic Stroke in Rats

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Hui Yang ◽  
Zhen Hui ◽  
Du Juan Sha ◽  
Yun Xu
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Cerebral Perfusion ◽  
Infarct Volume ◽  
Immunofluorescence Staining ◽  
Brain Barrier ◽  
Shh Pathway ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption

Background: The induction of angiogenesis and maintain the integrity of the blood brain barrier (BBB) after stroke may enhance neurorestorative processes. Panaxatriol Saponins (PTS), extracted from traditional Chinese herb Panaxnotoginseng, could noticeably prevent BBB disruption and promote angiogenesis in rodent stroke model. Methods: Middle cerebral artery occlusion (MCAO) model were applied to mimic acute stroke in vivo. Ischemic infarct volume and neurological functions were evaluated through 2,3,5-triphenyltetrazolium chloride (TTC) staining and Longa Scores (LS) respectively. The micro-PET scan was adopted to assess cerebral perfusion; evans blue extravasation assay was used to test BBB permeability; real time PCR and Western blot were used to evaluate the level of vascular growth factors, pro-inflammation factors, the components of Sonic hedgehog (Shh) pathway and NF-κB pathway. Enzyme Linked Immunosorbent Assay (ELISA) was used to detect the levels of pro-inflammation factors in the brain. The capillaries density in ischemic penumbra and tight junction in BBB were measured by immunofluorescence staining. Results: PTS treatment improved neurological function and reduced infarct volume in MCAO-rats. The result of micro-PET scan indicated that PTS could significantly enhance cerebral perfusion after MCAO operation. Treatment of PTS significantly attenuated BBB destruction. PTS could significantly increase the VEGF, Ang-1, VEGFR-2, Tie-2, CD31 and α-SMA mRNA expression at 3 d and 7 d after MCAO compared to vehicle group. Moreover, the expression levels of inflammation factors were decreased after PTS treatment. The co-immunofluorescence staining of α-SMA and Brdu with CD31 respectively showed that PTS promotes angiogenesis and endothelial cell proliferation after MCAO. Meanwhile, co-immunofluorescence staining of Claudin-5, Occludin and ZO-1 with CD31 respectively showed that PTS could protect tight junction from ischemia/reperfusion injury. PTS could also activate Shh pathway and inhibited NF-κB pathway. Conclusions: PTS alleviated ischemic stroke injury through attenuates blood-brain barrier disruption and promotes angiogenesis. PTS could be a potential medication for combating ischemic brain injury.

The immune system mediates blood-brain barrier damage; possible implications for pathophysiology of neuropsychiatric illnesses

1995 ◽  
Vol 7 (4) ◽  
pp. 114-121 ◽  
Author(s):  
Y.D. Van Der Werf ◽  
M.J.L. De Jongste ◽  
G.J. Ter Horst
Keyword(s):  
Myocardial Infarction ◽  
Immune System ◽  
Blood Brain Barrier ◽  
Immune Activation ◽  
Inflammatory Cytokine ◽  
Brain Barrier ◽  
Necrosis Factor Alpha ◽  
Blood Brain ◽  
Tnf Α ◽  
The Brain

SummaryIn this investigation the effects of immune activation on the brain are characterized. In order to study this, we used a model for chronic immune activation, the myocardial infarction, and intravenous injections with the pro-inflammatory cytokine Tumour Necrosis Factor alpha (TNF-α). The incentive for this study is the observation that myocardial infarction is accompanied by behavioural and neuronal abnormalities. The effects of myocardial infarction on the brain and its functioning are widespread. In order to examine the mechanism through which this interaction occurs, a group of rats underwent an experimentally induced myocardial infarction whereafter immunohistochemistry was performed on slices of the brain. This experiment revealed regional serum protein extravasation, pointing to leakage of the blood-brain barrier. This process occurred in certain cortical, subcortical and hindbrain areas in discrete patches. The leakage was co-localized with the expression of the immune activation marker ICAM-1. A second group of rats was therefore injected with TNF-α, a major pro-inflammatory cytokine, to assess the involvement of the immune system in the effects shown. This procedure rendered the same results. It is concluded that myocardial infarction may interfere with the integrity of the blood-brain barrier and possibly with brain functioning through activation of the immune system. The relevance for pathophysiological processes is discussed.

scholarly journals Neurological Complications Associated with the Blood-Brain Barrier Damage Induced by the Inflammatory Response During SARS-CoV-2 Infection

2020 ◽  
Author(s):  
Iván Alquisiras-Burgos ◽  
Irlanda Peralta-Arrieta ◽  
Luis Antonio Alonso-Palomares ◽  
Ana Elvira Zacapala-Gómez ◽  
Eric Genaro Salmerón-Bárcenas ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Blood Brain Barrier ◽  
Neurological Complications ◽  
Brain Barrier ◽  
Blood Brain ◽  
Blood Brain Barrier Damage
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