scholarly journals Inhibition of Bradykinin Receptor B1 Protects Mice from Focal Brain Injury by Reducing Blood–Brain Barrier Leakage and Inflammation

2010 ◽  
Vol 30 (8) ◽  
pp. 1477-1486 ◽  
Author(s):  
Furat Raslan ◽  
Tobias Schwarz ◽  
Sven G Meuth ◽  
Madeleine Austinat ◽  
Michael Bader ◽  
...  
Keyword(s):  
Brain Injury ◽  
Blood Brain Barrier ◽  
Brain Injuries ◽  
Neuronal Degeneration ◽  
Neuronal Damage ◽  
Brain Barrier ◽  
Lesion Volume ◽  
Wild Type ◽  
Edema Formation ◽  
Blood Brain

Kinins are proinflammatory and vasoactive peptides that are released during tissue damage and may contribute to neuronal degeneration, inflammation, and edema formation after brain injury by acting on discrete bradykinin receptors, B1R and B2R. We studied the expression of B1R and B2R and the effect of their inhibition on lesion size, blood–brain barrier (BBB) disruption, and inflammatory processes after a focal cryolesion of the right parietal cortex in mice. B1R and B2R gene transcripts were significantly induced in the lesioned hemispheres of wild-type mice ( P<0.05). The volume of the cortical lesions and neuronal damage at 24 h after injury in B1R −/− mice were significantly smaller than in wild-type controls (2.5±2.6 versus 11.5±3.9 mm3, P<0.001). Treatment with the B1R antagonist R-715 1 h after lesion induction likewise reduced lesion volume in wild-type mice (2.6±1.4 versus 12.2±6.1 mm3, P<0.001). This was accompanied by a remarkable reduction of BBB disruption and tissue inflammation. In contrast, genetic deletion or pharmacological inhibition of B2R had no significant impact on lesion formation or the development of brain edema. We conclude that B1R inhibition may offer a novel therapeutic strategy after acute brain injuries.

scholarly journals Circulating Tight-Junction Proteins Are Potential Biomarkers for Blood-Brain Barrier Function in a Model of Neonatal Hypoxic/Ischemic Brain Injury

2020 ◽  
Author(s):  
Axel Erik Andersson ◽  
Carina Mallard ◽  
Carl Joakim Ek
Keyword(s):  
Brain Injury ◽  
Blood Brain Barrier ◽  
Brain Injuries ◽  
Brain Barrier ◽  
Neonatal Brain ◽  
Ischemic Brain ◽  
Blood Brain ◽  
Hypoxia Ischemia ◽  
The Brain ◽  
Junction Proteins

Abstract BackgroundNeonatal hypoxia-ischemia often leads to lifelong disabilities with limited treatments currently available. The brain vasculature is an important factor in many neonatal brain pathologies but there is a lack of diagnostic tools to evaluate the brain vascular health of neonates in a clinical setting. Measurement of blood-brain barrier tight-junction proteins have shown promise as biomarkers for brain injury in the adult. Here we tested the biomarker potential of tight-junctions in the context of neonatal brain injury.MethodsThe levels of TJ-proteins (occluding, claudin-5, and zonula occludens-1) in both blood plasma and cerebrospinal fluid (CSF) as well as blood-brain barrier function were measured in a clinically relevant hypoxia/ischemia model in neonatal rats.ResultsTemporally acute elevated levels of occludin and claudin-5 could be measured in blood and CSF after hypoxia/ischemia with males generally having higher levels than females. The levels of claudin-5 in CSF correlated with the severity of the brain injury at 24h post- hypoxia/ischemia. Simultaneously, we detected early increase in blood-brain barrier-permeability at 6 and 24h after hypoxia/ischemia.ConclusionsLevels of circulating claudin-5 and occludin are increased after hypoxic/ischemic brain injuries and blood-brain barrier-impairment and have promise as early biomarkers for cerebral vascular health and as a tool for risk assessment of neonatal brain injuries.

The Permissive Nature of Blood Brain Barrier (BBB) Opening in Edema Formation Following Traumatic Brain Injury

2000 ◽  
pp. 125-129 ◽  
Author(s):  
A. Beaumont ◽  
Anthony Marmarou ◽  
K. Hayasaki ◽  
P. Barzo ◽  
P. Fatouros ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Edema Formation ◽  
Blood Brain ◽  
Bbb Opening

scholarly journals Circulating tight-junction proteins are potential biomarkers for blood–brain barrier function in a model of neonatal hypoxic/ischemic brain injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
E. Axel Andersson ◽  
Carina Mallard ◽  
C. Joakim Ek
Keyword(s):  
Brain Injury ◽  
Blood Brain Barrier ◽  
Brain Injuries ◽  
Vascular Dysfunction ◽  
Brain Barrier ◽  
Neonatal Brain ◽  
Ischemic Brain ◽  
Blood Brain ◽  
Hypoxia Ischemia ◽  
The Brain

Abstract Background Neonatal encephalopathy often leads to lifelong disabilities with limited treatments currently available. The brain vasculature is an important factor in many neonatal neurological disorders but there is a lack of diagnostic tools to evaluate the brain vascular dysfunction of neonates in the clinical setting. Measurement of blood–brain barrier tight-junction (TJ) proteins have shown promise as biomarkers for brain injury in the adult. Here we tested the biomarker potential of tight-junctions in the context of neonatal brain injury. Methods The levels of TJ-proteins (occluding, claudin-5, and zonula occludens protein 1) in both blood plasma and cerebrospinal fluid (CSF) as well as blood–brain barrier function via 14C-sucrose (342 Da) and Evans blue extravasation were measured in a hypoxia/ischemia brain-injury model in neonatal rats. Results Time-dependent changes of occludin and claudin-5 levels could be measured in blood and CSF after hypoxia/ischemia with males generally having higher levels than females. The levels of claudin-5 in CSF correlated with the severity of the brain injury at 24 h post- hypoxia/ischemia. Simultaneously, we detected early increase in blood–brain barrier-permeability at 6 and 24 h after hypoxia/ischemia. Conclusions Levels of circulating claudin-5 and occludin are increased after hypoxic/ischemic brain injuries and blood–brain barrier-impairment and have promise as early biomarkers for cerebral vascular dysfunction and as a tool for risk assessment of neonatal brain injuries.

scholarly journals Application of neuroprotectors in severe brain injuries

2011 ◽  
Vol 10 (5) ◽  
pp. 36-40
Author(s):  
O. Ye. Vaizova ◽  
N. A. Zautner ◽  
V. M. Alifirova ◽  
D. V. Kolmakov ◽  
Ye. L. Golovina ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Blood Brain Barrier ◽  
Blood Concentration ◽  
Brain Injuries ◽  
Neuron Specific Enolase ◽  
Brain Barrier ◽  
Blood Brain ◽  
Neuroprotective Therapy

Blood concentration of protein S100 was been decreased with choline-liked neuroprotectors citicoline and choline alfoscerate in clinical trial 52 patients in early day after stroke. Concentration of neuron-specific enolase was been decreased with three month mildronat therapy in blood of 16 patients with traumatic brain injury. Neuroprotective therapy has stabilization of blood-brain barrier as result.

scholarly journals Structural disruption of the blood–brain barrier in repetitive primary blast injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Gozde Uzunalli ◽  
Seth Herr ◽  
Alexandra M. Dieterly ◽  
Riyi Shi ◽  
L. Tiffany Lyle
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Blood Brain Barrier ◽  
Neuronal Degeneration ◽  
Blast Injury ◽  
Blast Waves ◽  
Brain Barrier ◽  
Health Concern ◽  
Primary Blast ◽  
Blood Brain

Abstract Background Blast-induced traumatic brain injury (bTBI) is a growing health concern due to the increased use of low-cost improvised explosive devices in modern warfare. Mild blast exposures are common amongst military personnel; however, these women and men typically do not have adequate recovery time from their injuries due to the transient nature of behavioral symptoms. bTBI has been linked to heterogeneous neuropathology, including brain edema, neuronal degeneration and cognitive abnormalities depending on the intensity of blast overpressure and frequency. Recent studies have reported heterogeneity in blood–brain barrier (BBB) permeability following blast injury. There still remains a limited understanding of the pathologic changes in the BBB following primary blast injuries. In this study, our goal was to elucidate the pathologic pattern of BBB damage through structural analysis following single and repetitive blast injury using a clinically relevant rat model of bTBI. Methods A validated, open-ended shock tube model was used to deliver single or repetitive primary blast waves. The pathology of the BBB was assessed using immunofluorescence and immunohistochemistry assays. All data were analyzed using the one-way ANOVA test. Results We have demonstrated that exposure to repetitive blast injury affects the desmin-positive and CD13-positive subpopulations of pericytes in the BBB. Changes in astrocytes and microglia were also detected. Conclusion This study provides analysis of the BBB components after repetitive blast injury. These results will be critical as preventative and therapeutic strategies are established for veterans recovering from blast-induced traumatic brain injury.

scholarly journals DHA Attenuates Cerebral Edema Following Traumatic Brain Injury via the Reduction in Blood–Brain Barrier Permeability

2020 ◽  
Vol 21 (17) ◽  
pp. 6291
Author(s):  
Zhuo-Hao Liu ◽  
Nan-Yu Chen ◽  
Po-hsun Tu ◽  
Chen-Te Wu ◽  
Shao-Chieh Chiu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Blood Brain Barrier ◽  
Temporal Analysis ◽  
Brain Barrier ◽  
Functional Improvement ◽  
Post Injury ◽  
Edema Formation ◽  
Mortality And Morbidity ◽  
Blood Brain

Traumatic brain injury (TBI) could result in edema and cause an increase in intracranial pressure of the brain resulting in mortality and morbidity. Although there is hyperosmolarity therapy available for this pathophysiological event, it remains controversial. Recently, several groups have shown docosahexaenoic acid (DHA) to improve functional and histological outcomes following brain injury based on reduction of neuroinflammation and apoptosis. However, the effect of DHA on blood–brain barrier (BBB) dysfunction after brain injury has not been fully studied. Here, a controlled cortical impact rat model was used to test the effect of a single dose of DHA administered 30 min post injury. Modified neurological severity score (mNSS) and forelimb asymmetry were used to determine the functional outcomes. Neuroimaging and histology were used to characterize the edema and BBB dysfunction. The study showed that DHA-treated TBI rats had better mNSS and forelimb asymmetry score than vehicle-treated TBI rats. Temporal analysis of edema using MRI revealed a significant reduction in edema level with DHA treatment compared to vehicle in TBI rats. Histological analysis using immunoglobulin G (IgG) extravasation showed that there was less extravasation, which corresponded with a reduction in aquaporin 4 and astrocytic metalloprotease 9 expression, and greater endothelial occludin expression in the peri-contusional site of the TBI rat brain treated with DHA in comparison to vehicle treatment. In conclusion, the study shows that DHA can exert its functional improvement by prevention of the edema formation via prevention of BBB dysfunction after TBI.

ApoE deficiency leads to a progressive age-dependent blood-brain barrier leakage

2007 ◽  
Vol 292 (4) ◽  
pp. C1256-C1262 ◽  
Author(s):  
Ali Hafezi-Moghadam ◽  
Kennard L. Thomas ◽  
Denisa D. Wagner
Keyword(s):  
Bone Marrow ◽  
Blood Brain Barrier ◽  
Neuronal Damage ◽  
Brain Regions ◽  
Brain Barrier ◽  
Chimeric Mice ◽  
Wild Type ◽  
Blood Brain ◽  
Age Related ◽  
Age Dependent

Previously, we reported a defect in the blood-brain barrier (BBB) of apolipoprotein E-deficient (apoE−/−) mice ( 24 ). Here, we investigate BBB permeability in wild-type (WT) and apoE−/− mice as a function of age. Both WT and apoE−/− mice showed significantly increased cortical BBB leakage with age. However, in apoE−/− mice, the leakage increased at a 3.7× higher rate compared with WT mice. Surprisingly, the cerebellum showed significantly more leakage than other brain regions across age, while there was no difference between the two hemispheres. To determine the contribution of tissue- vs. blood-borne apoE to vascular permeability, we generated chimeric mice by bone marrow transplantation and measured their BBB leakage. These experiments suggest that both blood- and tissue-derived apoE are equally important for BBB function. In sum, we find an age-dependent defect in the BBB that is exacerbated in apoE−/− mice. Since vascular defects are found in patients with age-related neurodegenerative diseases, such as Alzheimer's, age-related BBB leakage could underlie these defects and may thus be an important contributor to the cumulative neuronal damage of these diseases.

scholarly journals Traumatic Brain Injury and Blood–Brain Barrier (BBB): Underlying Pathophysiological Mechanisms and the Influence of Cigarette Smoking as a Premorbid Condition

2020 ◽  
Vol 21 (8) ◽  
pp. 2721 ◽  
Author(s):  
Farzane Sivandzade ◽  
Faleh Alqahtani ◽  
Luca Cucullo
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Blood Brain Barrier ◽  
Molecular Mechanisms ◽  
Brain Barrier ◽  
Secondary Brain Injury ◽  
Edema Formation ◽  
Mortality And Morbidity ◽  
Blood Brain ◽  
Post Traumatic

Traumatic brain injury (TBI) is among the most pressing global health issues and prevalent causes of cerebrovascular and neurological disorders all over the world. In addition to the brain injury, TBI may also alter the systemic immune response. Thus, TBI patients become vulnerable to infections, have worse neurological outcomes, and exhibit a higher rate of mortality and morbidity. It is well established that brain injury leads to impairments of the blood–brain barrier (BBB) integrity and function, contributing to the loss of neural tissue and affecting the response to neuroprotective drugs. Thus, stabilization/protection of the BBB after TBI could be a promising strategy to limit neuronal inflammation, secondary brain damage, and acute neurodegeneration. Herein, we present a review highlighting the significant post-traumatic effects of TBI on the cerebrovascular system. These include the loss of BBB integrity and selective permeability, impact on BBB transport mechanisms, post-traumatic cerebral edema formation, and significant pathophysiological factors that may further exacerbate post-traumatic BBB dysfunctions. Furthermore, we discuss the post-traumatic impacts of chronic smoking, which has been recently shown to act as a premorbid condition that impairs post-TBI recovery. Indeed, understanding the underlying molecular mechanisms associated with TBI damage is essential to better understand the pathogenesis and progression of post-traumatic secondary brain injury and the development of targeted treatments to improve outcomes and speed up the recovery process. Therapies aimed at restoring/protecting the BBB may reduce the post-traumatic burden of TBI by minimizing the impairment of brain homeostasis and help to restore an optimal microenvironment to support neuronal repair.

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