scholarly journals Evidence for blood‐brain barrier Na‐K‐Cl cotransport, Na/H exchange and Na‐HCO 3 cotransport involvement in hyperglycemia exacerbation of cerebral edema formation in ischemic stroke (685.3)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Olga Chechneva ◽  
Natalie Yuen ◽  
Yi‐Chen Tsai ◽  
Yi‐Je Chen ◽  
Steven Anderson ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Cerebral Edema ◽  
Brain Barrier ◽  
Edema Formation ◽  
Blood Brain

scholarly journals Exacerbated brain edema in a rat streptozotocin model of hyperglycemic ischemic stroke: Evidence for involvement of blood–brain barrier Na–K–Cl cotransport and Na/H exchange

2018 ◽  
Vol 39 (9) ◽  
pp. 1678-1692 ◽  
Author(s):  
Natalie Y Yuen ◽  
Olga V Chechneva ◽  
Yi-Je Chen ◽  
Yi-Chen Tsai ◽  
Logan K Little ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Cerebral Edema ◽  
Artery Occlusion ◽  
Brain Barrier ◽  
Microvascular Endothelial Cell ◽  
Type I ◽  
Edema Formation ◽  
Blood Brain ◽  
Na Uptake

Cerebral edema is exacerbated in diabetic ischemic stroke through poorly understood mechanisms. We showed previously that blood–brain barrier (BBB) Na–K–Cl cotransport (NKCC) and Na/H exchange (NHE) are major contributors to edema formation in normoglycemic ischemic stroke. Here, we investigated whether hyperglycemia-exacerbated edema involves changes in BBB NKCC and NHE expression and/or activity and whether inhibition of NKCC or NHE effectively reduces edema and injury in a type I diabetic model of hyperglycemic stroke. Cerebral microvascular endothelial cell (CMEC) NKCC and NHE abundances and activities were determined by Western blot, radioisotopic flux and microspectrofluorometric methods. Cerebral edema and Na in rats subjected to middle cerebral artery occlusion (MCAO) were assessed by nuclear magnetic resonance methods. Hyperglycemia exposures of 1-7d significantly increased CMEC NKCC and NHE abundance and activity. Subsequent exposure to ischemic factors caused more robust increases in NKCC and NHE activities than in normoglycemic CMEC. MCAO-induced edema and brain Na uptake were greater in hyperglycemic rats. Intravenous bumetanide and HOE-642 significantly attenuated edema, brain Na uptake and ischemic injury. Our findings provide evidence that BBB NKCC and NHE contribute to increased edema in hyperglycemic stroke, suggesting that these Na transporters are promising therapeutic targets for reducing damage in diabetic stroke.

scholarly journals Cerebral Edema Formation After Stroke: Emphasis on Blood–Brain Barrier and the Lymphatic Drainage System of the Brain

2021 ◽  
Vol 15 ◽  
Author(s):  
Sichao Chen ◽  
Linqian Shao ◽  
Li Ma
Keyword(s):  
Blood Brain Barrier ◽  
Cerebral Edema ◽  
Lymphatic System ◽  
Vasogenic Edema ◽  
Lymphatic Vessels ◽  
Drainage System ◽  
Brain Barrier ◽  
Edema Formation ◽  
Blood Brain ◽  
The Brain

Brain edema is a severe stroke complication that is associated with prolonged hospitalization and poor outcomes. Swollen tissues in the brain compromise cerebral perfusion and may also result in transtentorial herniation. As a physical and biochemical barrier between the peripheral circulation and the central nervous system (CNS), the blood–brain barrier (BBB) plays a vital role in maintaining the stable microenvironment of the CNS. Under pathological conditions, such as ischemic stroke, the dysfunction of the BBB results in increased paracellular permeability, directly contributing to the extravasation of blood components into the brain and causing cerebral vasogenic edema. Recent studies have led to the discovery of the glymphatic system and meningeal lymphatic vessels, which provide a channel for cerebrospinal fluid (CSF) to enter the brain and drain to nearby lymph nodes and communicate with the peripheral immune system, modulating immune surveillance and brain responses. A deeper understanding of the function of the cerebral lymphatic system calls into question the known mechanisms of cerebral edema after stroke. In this review, we first discuss how BBB disruption after stroke can cause or contribute to cerebral edema from the perspective of molecular and cellular pathophysiology. Finally, we discuss how the cerebral lymphatic system participates in the formation of cerebral edema after stroke and summarize the pathophysiological process of cerebral edema formation after stroke from the two directions of the BBB and cerebral lymphatic system.

scholarly journals Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation

Blood ◽  
2012 ◽  
Vol 120 (19) ◽  
pp. 4082-4092 ◽  
Author(s):  
Friederike Langhauser ◽  
Eva Göb ◽  
Peter Kraft ◽  
Christian Geis ◽  
Joachim Schmitt ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Thrombus Formation ◽  
Therapeutic Interventions ◽  
Brain Barrier ◽  
Edema Formation ◽  
Kinin System ◽  
Local Inflammatory Response ◽  
Blood Brain ◽  
Blood Brain Barrier Damage

Abstract Thrombosis and inflammation are hallmarks of ischemic stroke still unamenable to therapeutic interventions. High-molecular-weight kininogen (KNG) is a central constituent of the contact-kinin system which represents an interface between thrombotic and inflammatory circuits and is critically involved in stroke development. Kng−/− mice are protected from thrombosis after artificial vessel wall injury and lack the proinflammatory mediator bradykinin. We investigated the consequences of KNG deficiency in models of ischemic stroke. Kng−/− mice of either sex subjected to transient middle cerebral artery occlusion developed dramatically smaller brain infarctions and less severe neurologic deficits without an increase in infarct-associated hemorrhage. This protective effect was preserved at later stages of infarction as well as in elderly mice. Targeting KNG reduced thrombus formation in ischemic vessels and improved cerebral blood flow, and reconstitution of KNG-deficient mice with human KNG or bradykinin restored clot deposition and infarct susceptibility. Moreover, mice deficient in KNG showed less severe blood-brain barrier damage and edema formation, and the local inflammatory response was reduced compared with controls. Because KNG appears to be instrumental in pathologic thrombus formation and inflammation but dispensable for hemostasis, KNG inhibition may offer a selective and safe strategy for combating stroke and other thromboembolic diseases.

scholarly journals Deficiency of Vasodilator-Stimulated Phosphoprotein (VASP) Increases Blood-Brain-Barrier Damage and Edema Formation after Ischemic Stroke in Mice

PLoS ONE ◽  
2010 ◽  
Vol 5 (12) ◽  
pp. e15106 ◽  
Author(s):  
Peter Kraft ◽  
Peter Michael Benz ◽  
Madeleine Austinat ◽  
Marc Elmar Brede ◽  
Kai Schuh ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Edema Formation ◽  
Blood Brain ◽  
Blood Brain Barrier Damage

Abstract P335: Post-Treatment Blood-Brain Barrier Disruption is Associated With Cerebral Edema and Extends Into Penumbral Tissue in Anterior Circulation Large Vessel Occlusion

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Felix Ng ◽  
Gagan Sharma ◽  
Leonid Churilov ◽  
Nawaf Yassi ◽  
Timothy Kleinig ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Cerebral Edema ◽  
Post Treatment ◽  
Large Vessel ◽  
Brain Barrier ◽  
Large Vessel Occlusion ◽  
Anterior Circulation ◽  
Vessel Occlusion ◽  
Blood Brain

Background: Blood Brain Barrier (BBB) disruption is central to vasogenic edema development after ischemia in preclinical studies. We investigated the relationship between BBB disruption and cerebral edema in patients receiving reperfusion therapies for anterior circulation large vessel occlusion. Methods: In a post-hoc pooled analysis of the Tenecteplase versus Alteplase before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) part 1 and 2 multicenter RCTs, the DWI lesion on 24h post-treatment MRI and peri-infarct salvaged penumbra derived from pre-treatment CT-Perfusion (CTP) were segmented and registered to 24h MR Perfusion. A validated permeability measure (percentage of measured cerebral blood volume lost due to T1 effect from gadolinium leakage across the BBB) was calculated for each ROI. The association between post-treatment BBB disruption in the infarct and cerebral edema assessed on a trichotomized ordinal scale of negligible (<1mm midline shift), mild (≥1 to <5mm) or severe (≥5mm) was analyzed using ordinal logistic regression. Results: Of 220 patients analyzed, median (IQR) BBB disruption was 2.36(1.4-4.1)% in the infarct, 1.61(1.0-2.6)% in salvaged penumbra and 0.98(0.7-1.5)% in normal brain (p<0.001). There were 119 (54.1%) patients with negligible, 90 (40.8%) mild and 11 (5.0%) severe cerebral edema at 24h. In multivariable analysis, infarct BBB disruption was associated with increased cerebral edema (cOR=1.11 per%, 95%CI 1.02-1.21;p=0.012, adjusted for age, admission NIHSS and reperfusion (mTICI2b/3 or >50% reperfusion on early CTP 2h post-lysis). Infarct BBB disruption correlated with follow-up infarct volume (rho=0.37;p<0.001), and was associated with parenchymal hematoma (aOR=1.18, 95%CI 1.00-1.40;p=0.048) and worse outcome assessed on 90-day modified Rankin Scale (cOR=1.16 per%, 95%CI 1.08-1.26;p<0.001, adjusted for age, admission NIHSS and reperfusion). Conclusions: BBB disruption after reperfusion treatment extends beyond the infarct lesion, and is associated with cerebral edema development, hemorrhagic transformation and poor outcome. Further studies to evaluate BBB integrity as an imaging biomarker and potential therapeutic target in malignant cerebral edema after ischemic stroke are needed.

Dimethyl fumarate attenuates cerebral edema formation by protecting the blood–brain barrier integrity

2015 ◽  
Vol 266 ◽  
pp. 99-111 ◽  
Author(s):  
Reiner Kunze ◽  
Andrés Urrutia ◽  
Angelika Hoffmann ◽  
Hui Liu ◽  
Xavier Helluy ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Cerebral Edema ◽  
Dimethyl Fumarate ◽  
Brain Barrier ◽  
Edema Formation ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity

scholarly journals Sustained Opening of the Blood-Brain Barrier with Progressive Accumulation of White Matter Hyperintensities Following Ischemic Stroke

2019 ◽  
Vol 9 (1) ◽  
pp. 16 ◽  
Author(s):  
Imama Naqvi ◽  
Emi Hitomi ◽  
Richard Leigh
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Stroke ◽  
Blood Brain Barrier ◽  
White Matter Hyperintensities ◽  
Brain Barrier ◽  
Common Finding ◽  
Blood Brain ◽  
History Of ◽  
Iv Tpa

Objective: To report a patient in whom an acute ischemic stroke precipitated chronic blood-brain barrier (BBB) disruption and expansion of vascular white matter hyperintensities (WMH) into regions of normal appearing white matter (NAWM) during the following year. Background: WMH are a common finding in patients with vascular risk factors such as a history of stroke. The pathophysiology of WMH is not fully understood; however, there is growing evidence to suggest that the development of WMH may be preceded by the BBB disruption in the NAWM. Methods: We studied a patient enrolled in the National Institutes of Health Natural History of Stroke Study who was scanned with magnetic resonance imaging (MRI) after presenting to the emergency room with an acute stroke. After a treatment with IV tPA, she underwent further MRI scanning at 2 h, 24 h, 5 days, 30 days, 90 days, 6 months, and 1-year post stroke. BBB permeability images were generated from the perfusion weighted imaging (PWI) source images. MRIs from each time point were co-registered to track changes in BBB disruption and WMH over time. Results: An 84-year-old woman presented after acute onset right hemiparesis, right-sided numbness and aphasia with an initial NIHSS of 13. MRI showed diffusion restriction in the left frontal lobe and decreased blood flow on perfusion imaging. Fluid attenuated inversion recovery (FLAIR) imaging showed bilateral confluent WMH involving the deep white matter and periventricular regions. She was treated with IV tPA without complication and her NIHSS improved initially to 3 and ultimately to 0. Permeability maps identified multiple regions of chronic BBB disruption remote from the acute stroke, predominantly spanning the junction of WMH and NAWM. The severity of BBB disruption was greatest at 24 h after the stroke but persisted on subsequent MRI scans. Progression of WMH into NAWM over the year of observation was detected bilaterally but was most dramatic in the regions adjacent to the initial stroke. Conclusions: WMH-associated BBB disruption may be exacerbated by an acute stroke, even in the contralateral hemisphere, and can persist for months after the initial event. Transformation of NAWM to WMH may be evident in areas of BBB disruption within a year after the stroke. Further studies are needed to investigate the relationship between chronic BBB disruption and progressive WMH in patients with a history of cerebrovascular disease and the potential for acute stroke to trigger or exacerbate the process leading to the development of WMH.

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.

Sign in / Sign up

Export Citation Format

Share Document