scholarly journals The Relationship Between Penumbral Tissue and Blood-Brain Barrier Disruption in Acute Stroke Patients Presenting in an Extended Time Window

2020 ◽  
Vol 11 ◽  
Author(s):  
Parisa Heidari ◽  
Sarah Blayney ◽  
Jarrhett Butler ◽  
Emi Hitomi ◽  
Marie Luby ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Time Window ◽  
Brain Barrier ◽  
Extended Time ◽  
Stroke Patients ◽  
Ischemic Lesion ◽  
Blood Brain ◽  
The Mean ◽  
Target Profile ◽  
The Relationship

Background: Penumbral brain tissue identified with multimodal imaging can be salvaged with reperfusion in an extended time window. The risk of severe hemorrhagic complications after reperfusion therapy increases with worsening disruption of the blood-brain barrier (BBB). The relationship between penumbral tissue and BBB disruption has not been previously studied.Methods: Stroke patients presenting in an extended time window without a large vessel occlusion who underwent diffusion-perfusion MRI within 24 h of last-seen-normal were included. The volume of penumbral tissue was calculated using mismatch on MRI. Mean permeability derangement (MPD) of the BBB was measured within the ischemic lesion. A target profile (TP) for treatment was defined based on the EXTEND trial.Results: 222 patients were included with a median age of 73 and 55% women. The median NIHSS was 6, the mean core volume was 14 ml, the mean ischemic volume was 47 mL and the mean mismatch volume was 33 mL. Higher MPD was significantly associated with less mismatch volume (p = 0.001). A target profile was associated with lower MPD (OR 0.97; CI 0.96:0.99; p < 0.001). Of the 105 patients who had a TP, 31 (30%) had a MPD > 20% suggesting an increased risk of hemorrhage. Thus, 33% (74/222) of patients had a favorable profile for benefit and safety.Conclusions: Patients presenting in an extended time window with a favorable penumbral profile for treatment have less severe BBB disruption. Up to a third of patients who currently go untreated could be considered for enrollment in a clinical trial of thrombolysis in an extended time window.

scholarly journals Blood-brain barrier integrity of stroke patients presenting in an extended time window

BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jarrhett Butler ◽  
Parisa Heidari ◽  
Sarah Blayney ◽  
Emi Hitomi ◽  
Marie Luby ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Time Window ◽  
Brain Barrier ◽  
Extended Time ◽  
Stroke Patients ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity

scholarly journals Can CRP affect the blood-brain barrier during acute ischemic stroke?

2015 ◽  
Vol 125 (2) ◽  
pp. 99-102
Author(s):  
Joanna Bielewicz ◽  
Jacek Kurzepa ◽  
Elżbieta Czekajska-Chehab ◽  
Piotr Kamieniak ◽  
Beata Daniluk ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Clinical Status ◽  
Active Role ◽  
Neurological Status ◽  
Brain Barrier ◽  
Reactive Protein ◽  
Blood Brain ◽  
The Mean ◽  
High Level ◽  
The Relationship

Abstract Introduction. Ischemic strokes (IS) are one of the main causes of death and disabilities around the globe. Therefore, there is a huge need for researching the pathogenesis of IS. The C-reactive protein (CRP) plays a role during inflammatory processes. Results of some studies conducted on animal models indicate that CRP affects the blood-brain barrier (BBB) stability during IS. The presence of S100BB protein can be considered as an indication of BBB injury. Aim. The purpose of this study was to discover the relationship between CRP and S100BB protein. Material and methods. The study looked at fifty four IS patients, with the disease confirmed by computer tomography (CT). The clinical status was evaluated on the 1st, 3rd, 5th, 10th day and 3 months following the onset of IS. Neurological status was estimated using the National Institute of Health Stroke Scale (NIHSS). Patients’ disability level was determined, using Modified Rankin Scale (mRS) and Barthel Index (BI). The volume of ischemic focus was calculated on the 10th day after the stroke, using CT. The levels of CRP and S100BB were evaluated on 1st, 3rd, 5th and 10th day after the stroke onset with usage of ELISA method. Results. The mean level of CRP and its concentration on the 1st, 3rd, 5th and 10th day directly correlates with a deteriorated clinical status, as measured with the use of NIHSS, BI and mRS on day 10 and 3 months after the onset of IS. We found a correlation with the mean CRP level and bigger volume of ischemic injury. The mean CRP level correlated with the mean level of S100BB protein. In the group of patients with low CRP (0.51-24.68 mg/mL) the level of S100BB and the volume of ischemic focus were lower than in the group with a high level of CRP (24.69-209 mg/mL). Conclusions. CRP can be considered as a predictor of a worse clinical outcome after stroke. The relationship between CRP and S100BB protein can suggest the active role of CRP during IS

scholarly journals Plasma and cerebrospinal fluid inflammation and the blood-brain barrier in older surgical patients: the Role of Inflammation after Surgery for Elders (RISE) study

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Sarinnapha M. Vasunilashorn ◽  
◽  
Long H. Ngo ◽  
Simon T. Dillon ◽  
Tamara G. Fong ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Plasma Levels ◽  
Inflammatory Markers ◽  
Brain Barrier ◽  
Markers Of Inflammation ◽  
Blood Brain ◽  
Csf Levels ◽  
The Relationship

Abstract Background Our understanding of the relationship between plasma and cerebrospinal fluid (CSF) remains limited, which poses an obstacle to the identification of blood-based markers of neuroinflammatory disorders. To better understand the relationship between peripheral and central nervous system (CNS) markers of inflammation before and after surgery, we aimed to examine whether surgery compromises the blood-brain barrier (BBB), evaluate postoperative changes in inflammatory markers, and assess the correlations between plasma and CSF levels of inflammation. Methods We examined the Role of Inflammation after Surgery for Elders (RISE) study of adults aged ≥ 65 who underwent elective hip or knee surgery under spinal anesthesia who had plasma and CSF samples collected at baseline and postoperative 1 month (PO1MO) (n = 29). Plasma and CSF levels of three inflammatory markers previously identified as increasing after surgery were measured using enzyme-linked immunosorbent assay: interleukin-6 (IL-6), C-reactive protein (CRP), and chitinase 3-like protein (also known as YKL-40). The integrity of the BBB was computed as the ratio of CSF/plasma albumin levels (Qalb). Mean Qalb and levels of inflammation were compared between baseline and PO1MO. Spearman correlation coefficients were used to determine the correlation between biofluids. Results Mean Qalb did not change between baseline and PO1MO. Mean plasma and CSF levels of CRP and plasma levels of YKL-40 and IL-6 were higher on PO1MO relative to baseline, with a disproportionally higher increase in CRP CSF levels relative to plasma levels (CRP tripled in CSF vs. increased 10% in plasma). Significant plasma-CSF correlations for CRP (baseline r = 0.70 and PO1MO r = 0.89, p < .01 for both) and IL-6 (PO1MO r = 0.48, p < .01) were observed, with higher correlations on PO1MO compared with baseline. Conclusions In this elective surgical sample of older adults, BBB integrity was similar between baseline and PO1MO, plasma-CSF correlations were observed for CRP and IL-6, plasma levels of all three markers (CRP, IL-6, and YKL-40) increased from PREOP to PO1MO, and CSF levels of only CRP increased between the two time points. Our identification of potential promising plasma markers of inflammation in the CNS may facilitate the early identification of patients at greatest risk for neuroinflammation and its associated adverse cognitive outcomes.

Hyperosmolar blood-brain barrier disruption in baboons: an in vivo study using positron emission tomography and rubidium-82

1996 ◽  
Vol 84 (3) ◽  
pp. 494-502 ◽  
Author(s):  
Bernhard Zünkeler ◽  
Richard E. Carson ◽  
Jeffrey Olson ◽  
Ronald G. Blasberg ◽  
Mary Girton ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Emission Tomography ◽  
Brain Barrier ◽  
Blood Brain ◽  
Positron Emission ◽  
The Mean ◽  
Rubidium 82

✓ Hyperosmolar blood-brain barrier (BBB) disruption remains controversial as an adjuvant therapy to increase delivery of water-soluble compounds to extracellular space in the brain in patients with malignant brain tumors. To understand the physiological effects of BBB disruption more clearly, the authors used positron emission tomography (PET) to study the time course of BBB permeability in response to the potassium analog rubidium-82 (82Rb, halflife 75 seconds) following BBB disruption in anesthetized adult baboons. Mannitol (25%) was injected into the carotid artery and PET scans were performed before and serially at 8- to 15-minute intervals after BBB disruption. The mean influx constant (K1), a measure of permeability-surface area product, in ipsilateral, mannitol-perfused mixed gray- and white-matter brain regions was 4.9 ± 2.4 µl/min/ml (± standard deviation) at baseline and increased more than 100% (ΔK1 = 9.4 ± 5.1 µl/min/ml, 18 baboons) in brain perfused by mannitol. The effect of BBB disruption on K1 correlated directly with the total amount of mannitol administered (p < 0.005). Vascular permeability returned to baseline with a halftime of 24.0 ± 14.3 minutes. The mean brain plasma volume rose by 0.57 ± 0.34 ml/100 ml in ipsilateral perfused brain following BBB disruption. This work provides a basis for the in vivo study of permeability changes induced by BBB disruption in human brain and brain tumors.

Blood-brain barrier dysfunction and extension of time window for thrombolysis: a limitation not evaluated

2021 ◽  
Vol 19 ◽  
Author(s):  
Antonio Siniscalchi ◽  
Roman Sztajzel ◽  
Sean Murphy ◽  
Giovambattista De Sarro ◽  
Luca Gallelli
Keyword(s):  
Blood Brain Barrier ◽  
Time Window ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain

scholarly journals Mesenchymal Stem/Stromal Cell Therapy in Blood–Brain Barrier Preservation Following Ischemia: Molecular Mechanisms and Prospects

2021 ◽  
Vol 22 (18) ◽  
pp. 10045
Author(s):  
Phuong Thao Do ◽  
Chung-Che Wu ◽  
Yung-Hsiao Chiang ◽  
Chaur-Jong Hu ◽  
Kai-Yun Chen
Keyword(s):  
Stem Cells ◽  
Blood Brain Barrier ◽  
Molecular Mechanisms ◽  
Time Window ◽  
Brain Regions ◽  
Brain Barrier ◽  
Therapeutic Effects ◽  
Pathophysiological Mechanism ◽  
Cell Based Therapy ◽  
Blood Brain

Ischemic stroke is the leading cause of mortality and long-term disability worldwide. Disruption of the blood–brain barrier (BBB) is a prominent pathophysiological mechanism, responsible for a series of subsequent inflammatory cascades that exacerbate the damage to brain tissue. However, the benefit of recanalization is limited in most patients because of the narrow therapeutic time window. Recently, mesenchymal stem cells (MSCs) have been assessed as excellent candidates for cell-based therapy in cerebral ischemia, including neuroinflammatory alleviation, angiogenesis and neurogenesis promotion through their paracrine actions. In addition, accumulating evidence on how MSC therapy preserves BBB integrity after stroke may open up novel therapeutic targets for treating cerebrovascular diseases. In this review, we focus on the molecular mechanisms of MSC-based therapy in the ischemia-induced prevention of BBB compromise. Currently, therapeutic effects of MSCs for stroke are primarily based on the fundamental pathogenesis of BBB breakdown, such as attenuating leukocyte infiltration, matrix metalloproteinase (MMP) regulation, antioxidant, anti-inflammation, stabilizing morphology and crosstalk between cellular components of the BBB. We also discuss prospective studies to improve the effectiveness of MSC therapy through enhanced migration into defined brain regions of stem cells. Targeted therapy is a promising new direction and is being prioritized for extensive research.

Selective blood-tumor barrier disruption by leukotrienes

1992 ◽  
Vol 77 (3) ◽  
pp. 407-410 ◽  
Author(s):  
Chung-Ching Chio ◽  
Takehiko Baba ◽  
Keith L. Black
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Normal Brain ◽  
Barrier Permeability ◽  
Content Type ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
The Mean ◽  
Fine Print

✓ The authors have previously reported that intracarotid infusion of 5 µg leukotriene C4 (LTC4) selectively increases blood-tumor barrier permeability in rat RG-2 tumors. In this study, rats harboring RG-2 tumors were given 15-minute intracarotid infusions of LTC4 at concentrations ranging from 0.5 µg to 50.0 µg (seven rats in each dose group). Blood-tumor and blood-brain barrier permeability were determined by quantitative autoradiography using 14C aminoisobutyric acid. The transfer constant for permeability (Ki) within the tumors was increased twofold by LTC4 doses of 2.5, 5.0, and 50.0 µg compared to vehicle alone (90.00 ±21.14, 92.68 ± 15.04, and 80.17 ± 16.15 vs. 39.37 ± 6.45 µl/gm/min, respectively; mean ± standard deviation; p < 0.01). No significant change in Ki within the tumors was observed at the 0.5-µg LTC4 dose. Blood-brain barrier permeability was selectively increased within the tumors. At no dose in this study did leukotrienes increase permeability within normal brain. To determine the duration of increased opening of the blood-tumor barrier by LTC4 administration, Ki was measured at 15, 30, and 60 minutes after termination of a 15-minute LTC4 infusion (seven rats at each time point). The mean Ki value was still high at 15 minutes (92.68 ± 15.04 µl/gm/min), but declined at 30 minutes (56.58 ± 12.50 µl/gm/min) and 60 minutes (55.40 ± 8.10 µl/gm/min) after the end of LTC4 infusion. Sulfidopeptide leukotrienes LTC4, LTD4, LTE4 and LTF4 were infused to compare their potency in opening the blood-tumor barrier. The mean leukotriene E4 was the most potent, increasing the permeability value 37½ fold compared with vehicle alone (139.86 ± 23.95 vs. 39.37 ± 6.45 µl/gm/min).

scholarly journals Blood-Brain Barrier Disruption by Lipopolysaccharide and Sepsis-Associated Encephalopathy

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoyao Peng ◽  
Zhixuan Luo ◽  
Shuang He ◽  
Luhua Zhang ◽  
Ying Li
Keyword(s):  
Blood Brain Barrier ◽  
Barrier Function ◽  
Vascular System ◽  
Brain Barrier ◽  
Inflammatory Factors ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Brain Barrier Disruption ◽  
The Relationship

As a complex multicellular structure of the vascular system at the central nervous system (CNS), the blood-brain barrier (BBB) separates the CNS from the system circulation and regulates the influx and efflux of substances to maintain the steady-state environment of the CNS. Lipopolysaccharide (LPS), the cell wall component of Gram-negative bacteria, can damage the barrier function of BBB and further promote the occurrence and development of sepsis-associated encephalopathy (SAE). Here, we conduct a literature review of the direct and indirect damage mechanisms of LPS to BBB and the relationship between these processes and SAE. We believe that after LPS destroys BBB, a large number of inflammatory factors and neurotoxins will enter and damage the brain tissue, which will activate brain immune cells to mediate inflammatory response and in turn further destroys BBB. This vicious circle will ultimately lead to the progression of SAE. Finally, we present a succinct overview of the treatment of SAE by restoring the BBB barrier function and summarize novel opportunities in controlling the progression of SAE by targeting the BBB.

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