scholarly journals Comparative Effects of Glucose- and Mannitol-Induced Osmolar Stress on Blood—Brain Barrier Function in Ovine Fetuses and Lambs

2011 ◽  
Vol 32 (1) ◽  
pp. 115-126 ◽  
Author(s):  
Barbara S Stonestreet ◽  
Grazyna B Sadowska ◽  
R Choudary Hanumara ◽  
Mihaela Petrache ◽  
Katherine H Petersson ◽  
...  
Keyword(s):  
Superior Colliculus ◽  
Blood Brain Barrier ◽  
Brain Regions ◽  
Brain Barrier ◽  
Transfer Constant ◽  
Blood Brain ◽  
Bbb Permeability ◽  
The Relationship ◽  
Segmented Regression Model ◽  
Colliculus Inferior

We examined the effects of hyperglycemic hyperosmolality on blood-brain barrier (BBB) permeability during development. We hypothesized that the barrier becomes more resistant to hyperglycemic hyperosmolality during development, and the immature BBB is more resistant to glucose than to mannitol hyperosmolality. We quantified the BBB response to hyperosmolality with the blood-to-brain transfer constant ( Ki) in immature fetuses, premature, and newborn lambs. Ki increased as a function of increases in osmolality. A segmented regression model described the relationship between Ki and osmolality. At lower osmolalities, changes in Ki were minimal but after a threshold, increases were linear. We examined responses of Ki to hyperglycemic hyperosmolality by comparing the thresholds and slopes of the second regression segments. Lower thresholds and steeper slopes indicate greater vulnerability to hyperosmolality. Thresholds increased ( P < 0.05) during development in pons and superior colliculus. Thresholds were higher ( P < 0.05) during glucose than mannitol hyperosmolality in thalamus, superior colliculus, inferior colliculus and medulla of premature lambs, and in cerebrum and cerebellum of newborns. We conclude that BBB permeability increased as a function of changes in glucose osmolality, the barrier becomes more resistant to glucose hyperosmolality in two brain regions during development, and the barrier is more resistant to glucose than to mannitol hyperosmolality in some brain regions of premature and newborn lambs.

Effects of acute hyperosmolality on blood-brain barrier function in ovine fetuses and lambs

2006 ◽  
Vol 291 (4) ◽  
pp. R1031-R1039 ◽  
Author(s):  
Barbara S. Stonestreet ◽  
Grazyna B. Sadowska ◽  
Joanne Leeman ◽  
R. Choudary Hanumara ◽  
Katherine H. Petersson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Blood Brain Barrier ◽  
Break Point ◽  
Brain Regions ◽  
Brain Barrier ◽  
Transfer Constant ◽  
Blood Brain ◽  
Bbb Permeability ◽  
The Relationship ◽  
Segmented Regression Model

We examined the effects of hyperosmolality on blood-brain barrier (BBB) permeability during development to test the vulnerability of the immature barrier to stress. The BBB response to hyperosmolality was quantified using the blood-to-brain transfer constant ( Ki) with α-aminoisobutyric acid in fetuses at 60% and 90% gestation, premature, newborn, and older lambs. Ki plotted against osmolality increased as a function of increases in osmolality in all groups and brain regions. The relationship was described ( P < 0.05) by a segmented regression model. At lower osmolalities, changes in Ki were minimal, but after a break point (threshold) was reached, the increase ( P < 0.05) was linear. We examined the responses of Ki to hyperosmolality within each brain region by comparing the thresholds and slopes of the second regression segment. Lower thresholds and higher slopes imply greater vulnerability to hyperosmolality in the younger groups. Thresholds increased ( P < 0.05) with development in the thalamus, superior colliculus, pons, and spinal cord, and slopes of the second regression segment decreased ( P < 0.05) in the cerebellum, hippocampus, inferior colliculus, medulla, and spinal cord. BBB resistance to hyperosmolality increased ( P < 0.05) with development in most brain regions. The pattern of the Ki plotted against osmolality was ( P < 0.05) heterogenous among brain regions in fetuses and premature and newborn lambs, but not in older lambs. We conclude that 1) BBB permeability increased as a function of changes in osmolality, 2) the barrier becomes more resistant to hyperosmolality during development, and 3) the permeability response to hyperosmolality is heterogenous among brain regions in fetuses and premature and newborn lambs.

Intracarotid Infusion of Leukotriene C4 Selectively Increases Blood-Brain Barrier Permeability after Focal Ischemia in Rats

1991 ◽  
Vol 11 (4) ◽  
pp. 638-643 ◽  
Author(s):  
Takehiko Baba ◽  
Keith L. Black ◽  
Kiyonobu Ikezaki ◽  
Kangnian Chen ◽  
Donald P. Becker
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Normal Brain ◽  
Brain Capillaries ◽  
Transfer Constant ◽  
Blood Brain ◽  
Mca Occlusion ◽  
Ischemic Tissue ◽  
Bbb Permeability ◽  
Glutamyl Transpeptidase

Intracarotid infusions of leukotriene C4 (LTC4) were used to open selectively the blood–brain barrier (BBB) in ischemic tissue after middle cerebral artery (MCA) occlusion in rats. BBB permeability was determined by quantitative autoradiography using [14C]aminoisobutyric acid. Seventy-two hours after MCA occlusion, LTC4 (4 μg total dose) infused into the carotid artery ipsilateral to the MCA occlusion selectively increased the unidirectional transfer constant for permeability K1 approximately threefold within core ischemic tissue and tissue adjacent to the ischemic core. No effect on BBB permeability was seen within nonischemic brain tissue or in ischemic tissue after only 24 h after MCA occlusion. γ-Glutamyl transpeptidase (γ-GTP) activity was decreased in capillaries in ischemic tissue at 48 and 72 h after infarction, compared to high γ-GTP in normal brain capillaries and moderate γ-GTP in capillaries in the ischemic tissue at 24 h after infarction. These findings suggest that normal brain capillaries resist the vasogenic effects of LTC4. In contrast, LTC4 increases permeability in capillaries of ischemic tissue, where γ-GTP is decreased. γ-Glutamyl transpeptidase, an enzyme that inactivates LTC4 to LTD4 and LTE4 to LTF4, may act as an “enzymatic barrier” in normal brain capillaries to leukotrienes.

scholarly journals Antibiotics-induced alterations in gut microbiol composition leads to blood-brain barrier permeability increase in rhesus monkeys

2020 ◽  
Author(s):  
Qiong Wu ◽  
Yingqian Zhang ◽  
Yinbing Zhang ◽  
Chunchao Xia ◽  
Qi Lai ◽  
...  
Keyword(s):  
Propionic Acid ◽  
Blood Brain Barrier ◽  
Rhesus Monkeys ◽  
Brain Barrier ◽  
Transfer Constant ◽  
Microbiome Composition ◽  
Blood Brain ◽  
Bbb Permeability ◽  
Permeability Increase ◽  
And Function

ABSTRACTBlood-brain barrier (BBB) contributes to maintenance of brain homeostasis. Gut microbiome composition affected BBB development and expression of tight junction proteins in rodents. However, we still do not know if there’s any direct effect of gut microbiol composition on BBB permeability and function in normal adult animals. In current study, we determined temporal and spatial change of BBB permeability in rhesus monkeys receiving either oral or intravenous amoxicillin-clavulanic acid (AC), by monitoring CSF/serum albumin ratio (AR) and the volume transfer constant (Ktrans). We showed that oral, but not intravenous AC led to a significant alteration in gut microbiol composition and increase of BBB permeability in all monkeys, especially in thalamus area. Acetic acid and propionic acid might play a pivotal role in this newly found communication between gut and central nervous system. Antibiotics-induced gut microbiol composition change, especially the decreasing of acetic and propionic acid producing phyla and genera, leads to increase of BBB permeability, which may contribute to a variety of neurological and psychological diseases.

scholarly journals Region-specific disruption of the blood-brain barrier following repeated inflammatory dural stimulation in a rat model of chronic trigeminal allodynia

Cephalalgia ◽  
2017 ◽  
Vol 38 (4) ◽  
pp. 674-689 ◽  
Author(s):  
Nathan T Fried ◽  
Christina R Maxwell ◽  
Melanie B Elliott ◽  
Michael L Oshinsky
Keyword(s):  
Blood Brain Barrier ◽  
Rat Model ◽  
Microglial Activation ◽  
Brain Regions ◽  
Brain Barrier ◽  
Sodium Fluorescein ◽  
Blood Brain ◽  
Bbb Permeability ◽  
The Impact ◽  
Trigeminal Sensitivity

Background The blood-brain barrier (BBB) has been hypothesized to play a role in migraine since the late 1970s. Despite this, limited investigation of the BBB in migraine has been conducted. We used the inflammatory soup rat model of trigeminal allodynia, which closely mimics chronic migraine, to determine the impact of repeated dural inflammatory stimulation on BBB permeability. Methods The sodium fluorescein BBB permeability assay was used in multiple brain regions (trigeminal nucleus caudalis (TNC), periaqueductal grey, frontal cortex, sub-cortex, and cortex directly below the area of dural activation) during the episodic and chronic stages of repeated inflammatory dural stimulation. Glial activation was assessed in the TNC via GFAP and OX42 immunoreactivity. Minocycline was tested for its ability to prevent BBB disruption and trigeminal sensitivity. Results No astrocyte or microglial activation was found during the episodic stage, but BBB permeability and trigeminal sensitivity were increased. Astrocyte and microglial activation, BBB permeability, and trigeminal sensitivity were increased during the chronic stage. These changes were only found in the TNC. Minocycline treatment prevented BBB permeability modulation and trigeminal sensitivity during the episodic and chronic stages. Discussion Modulation of BBB permeability occurs centrally within the TNC following repeated dural inflammatory stimulation and may play a role in migraine.

scholarly journals Region-specific permeability of the blood–brain barrier upon pericyte loss

2017 ◽  
Vol 37 (12) ◽  
pp. 3683-3694 ◽  
Author(s):  
Roberto Villaseñor ◽  
Basil Kuennecke ◽  
Laurence Ozmen ◽  
Michelle Ammann ◽  
Christof Kugler ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Regions ◽  
Brain Parenchyma ◽  
Brain Barrier ◽  
Regional Heterogeneity ◽  
Blood Brain ◽  
Specific Permeability ◽  
Bbb Permeability ◽  
Pericyte Loss ◽  
The Brain

The blood–brain barrier (BBB) regulates differing needs of the various brain regions by controlling transport of blood-borne components from the neurovascular circulation into the brain parenchyma. The mechanisms underlying region-specific transport across the BBB are not completely understood. Previous work showed that pericytes are key regulators of BBB function. Here we investigated whether pericytes influence BBB permeability in a region-specific manner by analysing the regional permeability of the BBB in the pdgf-b ret/ret mouse model of pericyte depletion. We show that BBB permeability is heterogeneous in pdgf-b ret/ret mice, being significantly higher in the cortex, striatum and hippocampus compared to the interbrain and midbrain. However, we show that this regional heterogeneity in BBB permeability is not explained by local differences in pericyte coverage. Region-specific differences in permeability were not associated with disruption of tight junctions but may result from changes in transcytosis across brain endothelial cells. Our data show that certain brain regions are able to maintain low BBB permeability despite substantial pericyte loss and suggest that additional, locally-acting mechanisms may contribute to control of transport.

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.

scholarly journals Dual Roles of Astrocyte-Derived Factors in Regulation of Blood-Brain Barrier Function after Brain Damage

2019 ◽  
Vol 20 (3) ◽  
pp. 571 ◽  
Author(s):  
Shotaro Michinaga ◽  
Yutaka Koyama
Keyword(s):  
Brain Damage ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Secondary Damage ◽  
The Central Nervous System ◽  
Bbb Permeability ◽  
Novel Therapeutic Strategies ◽  
Glial Derived Neurotrophic Factor ◽  
Endothelial Growth Factors

The blood-brain barrier (BBB) is a major functional barrier in the central nervous system (CNS), and inhibits the extravasation of intravascular contents and transports various essential nutrients between the blood and the brain. After brain damage by traumatic brain injury, cerebral ischemia and several other CNS disorders, the functions of the BBB are disrupted, resulting in severe secondary damage including brain edema and inflammatory injury. Therefore, BBB protection and recovery are considered novel therapeutic strategies for reducing brain damage. Emerging evidence suggests key roles of astrocyte-derived factors in BBB disruption and recovery after brain damage. The astrocyte-derived vascular permeability factors include vascular endothelial growth factors, matrix metalloproteinases, nitric oxide, glutamate and endothelin-1, which enhance BBB permeability leading to BBB disruption. By contrast, the astrocyte-derived protective factors include angiopoietin-1, sonic hedgehog, glial-derived neurotrophic factor, retinoic acid and insulin-like growth factor-1 and apolipoprotein E which attenuate BBB permeability resulting in recovery of BBB function. In this review, the roles of these astrocyte-derived factors in BBB function are summarized, and their significance as therapeutic targets for BBB protection and recovery after brain damage are discussed.

scholarly journals Pseudogene ACTBP2 increases blood–brain barrier permeability by promoting KHDRBS2 transcription through recruitment of KMT2D/WDR5 in Aβ1–42 microenvironment

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Qianshuo Liu ◽  
Xiaobai Liu ◽  
Defeng Zhao ◽  
Xuelei Ruan ◽  
Rui Su ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Vital Role ◽  
Brain Barrier ◽  
Blood Brain ◽  
Bbb Permeability ◽  
Novel Target ◽  
And Function

AbstractThe blood–brain barrier (BBB) has a vital role in maintaining the homeostasis of the central nervous system (CNS). Changes in the structure and function of BBB can accelerate Alzheimer’s disease (AD) development. β-Amyloid (Aβ) deposition is the major pathological event of AD. We elucidated the function and possible molecular mechanisms of the effect of pseudogene ACTBP2 on the permeability of BBB in Aβ1–42 microenvironment. BBB model treated with Aβ1–42 for 48 h were used to simulate Aβ-mediated BBB dysfunction in AD. We proved that pseudogene ACTBP2, RNA-binding protein KHDRBS2, and transcription factor HEY2 are highly expressed in ECs that were obtained in a BBB model in vitro in Aβ1–42 microenvironment. In Aβ1–42-incubated ECs, ACTBP2 recruits methyltransferases KMT2D and WDR5, binds to KHDRBS2 promoter, and promotes KHDRBS2 transcription. The interaction of KHDRBS2 with the 3′UTR of HEY2 mRNA increases the stability of HEY2 and promotes its expression. HEY2 increases BBB permeability in Aβ1–42 microenvironment by transcriptionally inhibiting the expression of ZO-1, occludin, and claudin-5. We confirmed that knocking down of Khdrbs2 or Hey2 increased the expression levels of ZO-1, occludin, and claudin-5 in APP/PS1 mice brain microvessels. ACTBP2/KHDRBS2/HEY2 axis has a crucial role in the regulation of BBB permeability in Aβ1–42 microenvironment, which may provide a novel target for the therapy of AD.

Osmotic Blood-Brain Barrier Modification and Combination Chemotherapy: Concurrent Tumor Regression in Areas of Barrier Opening and Progression in Brain Regions Distant to Barrier Opening

Neurosurgery ◽  
1984 ◽  
Vol 15 (3) ◽  
pp. 362-366 ◽  
Author(s):  
Edward A. Neuwelt ◽  
Suellen A. Hill ◽  
Eugene P. Frenkel
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Tumor Regression ◽  
Primary Cns Lymphoma ◽  
Brain Regions ◽  
Metastatic Carcinoma ◽  
Brain Barrier ◽  
Cns Lymphoma ◽  
Blood Brain ◽  
Barrier Opening

Abstract Chemotherapeutic drug delivery can be enhanced by administering drugs into the internal carotid or vertebral artery circulation after osmotic opening of the blood-brain barrier (BBB). As evidence of the clinical implications of this technique, radiographic documentation of central nervous system (CNS) tumor regression was observed in three patients concurrent with the development of new tumor nodule(s) in portions of the brain distant from the region of osmotic blood-brain barrier opening. These three patients, one with metastatic carcinoma of the breast, one with glioblastoma, and one with primary CNS lymphoma, highlight the importance of drug delivery to CNS malignancies.

scholarly journals Early Appearance of Activated Matrix Metalloproteinase-9 after Focal Cerebral Ischemia in Mice: A Possible Role in Blood—Brain Barrier Dysfunction

1999 ◽  
Vol 19 (9) ◽  
pp. 1020-1028 ◽  
Author(s):  
Yvan Gasche ◽  
Miki Fujimura ◽  
Yuiko Morita-Fujimura ◽  
Jean-Christophe Copin ◽  
Makoto Kawase ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Blood Brain Barrier ◽  
Focal Cerebral Ischemia ◽  
Vasogenic Edema ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Brain Barrier ◽  
Critical Event ◽  
Secondary Brain Injury ◽  
Blood Brain ◽  
Bbb Permeability

During cerebral ischemia blood–brain barrier (BBB) disruption is a critical event leading to vasogenic edema and secondary brain injury. Gelatinases A and B are matrix metalloproteinases (MMP) able to open the BBB. The current study analyzes by zymography the early gelatinases expression and activation during permanent ischemia in mice (n = 15). ProMMP-9 expression was significantly ( P < 0.001) increased in ischemic regions compared with corresponding contralateral regions after 2 hours of ischemia (mean 694.7 arbitrary units [AU], SD ± 238.4 versus mean 107.6 AU, SD ± 15.6) and remained elevated until 24 hours (mean 745,7 AU, SD ± 157.4). Moreover, activated MMP-9 was observed 4 hours after the initiation of ischemia. At the same time as the appearance of activated MMP-9, we detected by the Evan's blue extravasation method a clear increase of BBB permeability, Tissue inhibitor of metalloproteinase-1 was not modified during permanent ischemia at any time. The ProMMP-2 was significantly ( P < 0.05) increased only after 24 hours of permanent ischemia (mean 213.2 AU, SD ± 60.6 versus mean 94.6 AU, SD ± 13.3), and no activated form was observed. The appearance of activated MMP-9 after 4 hours of ischemia in correlation with BBB permeability alterations suggests that MMP-9 may play an active role in early vasogenic edema development after stroke.

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