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William A Banks - One of the best experts on this subject based on the ideXlab platform.

  • inter alpha inhibitor proteins attenuate lipopolysaccharide induced blood Brain Barrier disruption and downregulate circulating interleukin 6 in mice
    Journal of Cerebral Blood Flow and Metabolism, 2020
    Co-Authors: Aric F Logsdon, Xiaodi Chen, Barbara S. Stonestreet, Yow Pin Lim, Michelle A Erickson, Joseph Qiu, William A Banks
    Abstract:

    Circulating levels of inter-alpha inhibitor proteins change dramatically in acute inflammatory disorders, which suggest an important contribution to the immunomodulatory system. Human blood-derived inter-alpha inhibitor proteins are neuroprotective and improve survival of neonatal mice exposed to lipopolysaccharide. Lipopolysaccharide augments inflammatory conditions and disrupts the blood-Brain Barrier. There is a paucity of therapeutic strategies to treat blood-Brain Barrier dysfunction, and the neuroprotective effects of human blood-derived inter-alpha inhibitor proteins are not fully understood. To examine the therapeutic potential of inter-alpha inhibitor proteins, we administered human blood-derived inter-alpha inhibitor proteins to male and female CD-1 mice after lipopolysaccharide exposure and quantified blood-Brain Barrier permeability of intravenously injected 14C-sucrose and 99mTc-albumin. We hypothesized that human blood-derived inter-alpha inhibitor protein treatment would attenuate lipopolysaccharide-induced blood-Brain Barrier disruption and associated inflammation. Lipopolysaccharide increased blood-Brain Barrier permeability to both 14C-sucrose and 99mTc-albumin, but human blood-derived inter-alpha inhibitor protein treatment only attenuated increases in 14C-sucrose blood-Brain Barrier permeability in male mice. Lipopolysaccharide stimulated a more robust elevation of male serum inter-alpha inhibitor protein concentration compared to the elevation measured in female serum. Lipopolysaccharide administration also increased multiple inflammatory factors in serum and Brain tissue, including interleukin 6. Human blood-derived inter-alpha inhibitor protein treatment downregulated serum interleukin 6 levels, which were inversely correlated with serum inter-alpha inhibitor protein concentration. We conclude that inter-alpha inhibitor proteins may be neuroprotective through mechanisms of blood-Brain Barrier disruption associated with systemic inflammation.

  • pharmacologic manipulation of lysosomal enzyme transport across the blood Brain Barrier
    Journal of Cerebral Blood Flow and Metabolism, 2016
    Co-Authors: Akihiko Urayama, Jeffrey H Grubb, William S Sly, William A Banks
    Abstract:

    The adult blood-Brain Barrier, unlike the neonatal blood-Brain Barrier, does not transport lysosomal enzymes into Brain, making enzyme replacement therapy ineffective in treating the central nervous system symptoms of lysosomal storage diseases. However, enzyme transport can be re-induced with alpha-adrenergics. Here, we examined agents that are known to alter the blood-Brain Barrier transport of large molecules or to induce lysosomal enzyme transport across the blood-Brain Barrier ((±)epinephrine, insulin, retinoic acid, and lipopolysaccharide) in 2-week-old and adult mice. In 2-week-old adolescent mice, all these pharmacologic agents increased Brain and heart uptake of phosphorylated human β-glucuronidase. In 8-week-old adult mice, manipulations with (±)epinephrine, insulin, and retinoic acid were significantly effective on uptake by Brain and heart. The increased uptake of phosphorylated human β-glucuronidase was inhibited by mannose 6-phosphate for the agents (±)epinephrine and retinoic acid and by L-NG-nitroarginine methyl ester for the agent lipopolysaccharide in neonatal and adult mice. An in situ Brain perfusion study revealed that retinoic acid directly modulated the transport of phosphorylated human β-glucuronidase across the blood-Brain Barrier. The present study indicates that there are multiple opportunities to at least transiently induce phosphorylated human β-glucuronidase transport at the adult blood-Brain Barrier.

  • anti il 6 neutralizing antibody modulates blood Brain Barrier function in the ovine fetus
    The FASEB Journal, 2015
    Co-Authors: Jiyong Zhang, Erin E Cummings, John N Gaitanis, Grazyna B Sadowska, Oleksandr Makeyev, Xiaodi Chen, Walter G. Besio, Seon Yeong Park, Courtney A Bodge, William A Banks
    Abstract:

    Impaired blood-Brain Barrier function represents an important component of hypoxic-ischemic Brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-Brain Barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-Brain Barrier abnormalities have not been examined in the immature Brain in vivo. We generated pharmacologic quantities of ovine-specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal sheep at 126 days of gestation after exposure to Brain ischemia. Anti–IL-6 mAbs were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid, blood-Brain Barrier permeability was quantified using the blood-to-Brain transfer constant in Brain regions, and IL-6, tight junction proteins, and plasmalemma vesicle protein (PLVAP) were detected by Western immunoblot. Anti–IL-6 mAb infusions resulted in increases in mAb (P < 0.05) in plasma, Brain parenchym...

  • ischemia reperfusion impairs blood Brain Barrier function and alters tight junction protein expression in the ovine fetus
    Neuroscience, 2012
    Co-Authors: Xiaodi Chen, Erin E Cummings, Ilona Juan, John N Gaitanis, Grazyna B Sadowska, Oleksandr Makeyev, Walter G. Besio, Steven W Threlkeld, William A Banks, Barbara S. Stonestreet
    Abstract:

    The blood-Brain Barrier is a restrictive interface between the Brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-Brain Barrier. Hypoxic-ischemic damage to the blood-Brain Barrier could be an important component of fetal Brain injury. We hypothesized that increases in blood- Brain Barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impair- ment in blood-Brain Barrier function in the fetus. Blood- Brain Barrier function was quantified with the blood-to-Brain transfer constant (Ki) and tight junction proteins by Western immunoblot in fetal sheep at 127 days of gestation without ischemia, and 4, 24, or 48 h after ischemia. The largest increase in Ki (P < 0.05) was 4 h after ischemia. Occludin and claudin-5 expressions decreased at 4 h, but returned toward control levels 24 and 48 h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse corre- lations between Ki and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-Brain Barrier function after ischemia. We conclude that impaired blood-Brain Barrier function is an important component of hypoxic-ischemic Brain injury in the fetus, and that increases in quantitatively measured Barrier permeability (K

  • measurement of phosphorothioate oligodeoxynucleotide antisense transport across the blood Brain Barrier
    Methods of Molecular Biology, 2011
    Co-Authors: William A Banks
    Abstract:

    : Phosphorothioate oligodeoxynucleotides (PODNs) can act as antisense molecules, knocking down proteins. Many PODNs have the unusual characteristic of being transported across the blood-Brain Barrier by a saturable system. This means that PODNs injected intravenously can accumulate in the central nervous system in quantities sufficient to knock down proteins in Brain and the blood-Brain Barrier. A critical step in the development of PODNs that can be administered peripherally and knockdown proteins in the central nervous system is to determine the relation to the blood-Brain Barrier, specifically, does the PODN cross the blood-Brain Barrier and, if so, how fast and to what degree.

Catharina J M Klijn - One of the best experts on this subject based on the ideXlab platform.

  • blood Brain Barrier dysfunction in small vessel disease related intracerebral hemorrhage
    Frontiers in Neurology, 2018
    Co-Authors: Whitney M Freeze, Heidi I L Jacobs, Floris H B M Schreuder, Robert J Van Oostenbrugge, Walter H Backes, Frans R J Verhey, Catharina J M Klijn
    Abstract:

    Background and Purpose: Hypertensive vasculopathy and cerebral amyloid angiopathy are the two most common forms of cerebral small vessel disease. Both forms are associated with the development of primary intracerebral hemorrhage, but the pathophysiological mechanisms underlying spontaneous vessel rupture remain unknown. This work constitutes a systematic review on blood-Brain Barrier dysfunction in the etiology of spontaneous intracerebral hemorrhage due to cerebral small vessel disease. Methods: We searched Medline (1946-2018) and Embase (1974-2018) for animal and human studies reporting on blood-Brain Barrier dysfunction associated with intracerebral hemorrhage or cerebral microbleeds. Results: Of 26 eligible studies, 10 were animal studies and 16 were in humans. The authors found indications for blood-Brain Barrier dysfunction in all four animal studies addressing hypertensive vasculopathy-related intracerebral hemorrhage (n = 32 hypertensive animals included in all four studies combined), and in four of six studies on cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 47). Of the studies in humans, five of six studies in patients with cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 117) and seven out of nine studies examining intracerebral hemorrhage with mixed or unspecified underlying etiology (n = 489) found indications for blood-Brain Barrier dysfunction. One post-mortem study in hypertensive vasculopathy-related intracerebral hemorrhage (n = 82) found no evidence for blood-Brain Barrier abnormalities. Conclusions: Signs of blood-Brain Barrier dysfunction were found in 20 out of 26 studies. Blood-Brain Barrier integrity deserves further investigation with a view to identification of potential treatment targets for spontaneous intracerebral hemorrhage.

  • blood Brain Barrier dysfunction in small vessel disease related intracerebral hemorrhage
    Frontiers in Neurology, 2018
    Co-Authors: Whitney M Freeze, Heidi I L Jacobs, Floris H B M Schreuder, Walter H Backes, Frans R J Verhey, Robert J Van Oostenbrugge, Catharina J M Klijn
    Abstract:

    Background and purpose: Hypertensive vasculopathy and cerebral amyloid angiopathy are the two most common forms of cerebral small vessel disease. Both forms are associated with the development of primary intracerebral hemorrhage, but the pathophysiological mechanisms underlying spontaneous vessel rupture remain unknown. This work constitutes a systematic review on blood-Brain Barrier dysfunction in the etiology of spontaneous intracerebral hemorrhage due to cerebral small vessel disease. Methods: We searched Medline (1946-2018) and Embase (1974-2018) for animal and human studies reporting on blood-Brain Barrier dysfunction associated with intracerebral hemorrhage or cerebral microbleeds. Results: Of twenty-six eligible studies, ten were animal studies and sixteen were in humans. The authors found indications for blood-Brain Barrier dysfunction in all four animal studies addressing hypertensive vasculopathy-related intracerebral hemorrhage (n=32 hypertensive animals included in all four studies combined), and in four of six studies on cerebral amyloid angiopathy-related intracerebral hemorrhage (n=47). Of the studies in humans, five of six studies in patients with cerebral amyloid angiopathy-related intracerebral hemorrhage (n=117) and seven out of nine studies examining intracerebral hemorrhage with mixed or unspecified underlying etiology (n=489) found indications for blood-Brain Barrier dysfunction. One post-mortem study in hypertensive vasculopathy-related intracerebral hemorrhage (n=82) found no evidence for blood-Brain Barrier abnormalities. Conclusions: Signs of blood-Brain Barrier dysfunction were found in twenty out of twenty-six studies. Blood-Brain Barrier integrity deserves further investigation with a view to identification of potential treatment targets for spontaneous intracerebral hemorrhage.

  • Image_1_Blood-Brain Barrier Dysfunction in Small Vessel Disease Related Intracerebral Hemorrhage.TIFF
    2018
    Co-Authors: Whitney M Freeze, Heidi I L Jacobs, Floris H B M Schreuder, Robert J Van Oostenbrugge, Walter H Backes, Frans R J Verhey, Catharina J M Klijn
    Abstract:

    Background and Purpose: Hypertensive vasculopathy and cerebral amyloid angiopathy are the two most common forms of cerebral small vessel disease. Both forms are associated with the development of primary intracerebral hemorrhage, but the pathophysiological mechanisms underlying spontaneous vessel rupture remain unknown. This work constitutes a systematic review on blood-Brain Barrier dysfunction in the etiology of spontaneous intracerebral hemorrhage due to cerebral small vessel disease.Methods: We searched Medline (1946–2018) and Embase (1974–2018) for animal and human studies reporting on blood-Brain Barrier dysfunction associated with intracerebral hemorrhage or cerebral microbleeds.Results: Of 26 eligible studies, 10 were animal studies and 16 were in humans. The authors found indications for blood-Brain Barrier dysfunction in all four animal studies addressing hypertensive vasculopathy-related intracerebral hemorrhage (n = 32 hypertensive animals included in all four studies combined), and in four of six studies on cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 47). Of the studies in humans, five of six studies in patients with cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 117) and seven out of nine studies examining intracerebral hemorrhage with mixed or unspecified underlying etiology (n = 489) found indications for blood-Brain Barrier dysfunction. One post-mortem study in hypertensive vasculopathy-related intracerebral hemorrhage (n = 82) found no evidence for blood-Brain Barrier abnormalities.Conclusions: Signs of blood-Brain Barrier dysfunction were found in 20 out of 26 studies. Blood-Brain Barrier integrity deserves further investigation with a view to identification of potential treatment targets for spontaneous intracerebral hemorrhage.

Walter G. Besio - One of the best experts on this subject based on the ideXlab platform.

  • anti il 6 neutralizing antibody modulates blood Brain Barrier function in the ovine fetus
    The FASEB Journal, 2015
    Co-Authors: Jiyong Zhang, Erin E Cummings, John N Gaitanis, Grazyna B Sadowska, Oleksandr Makeyev, Xiaodi Chen, Walter G. Besio, Seon Yeong Park, Courtney A Bodge, William A Banks
    Abstract:

    Impaired blood-Brain Barrier function represents an important component of hypoxic-ischemic Brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-Brain Barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-Brain Barrier abnormalities have not been examined in the immature Brain in vivo. We generated pharmacologic quantities of ovine-specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal sheep at 126 days of gestation after exposure to Brain ischemia. Anti–IL-6 mAbs were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid, blood-Brain Barrier permeability was quantified using the blood-to-Brain transfer constant in Brain regions, and IL-6, tight junction proteins, and plasmalemma vesicle protein (PLVAP) were detected by Western immunoblot. Anti–IL-6 mAb infusions resulted in increases in mAb (P < 0.05) in plasma, Brain parenchym...

  • anti il 6 neutralizing antibody modulates blood Brain Barrier function in the ovine fetus
    The FASEB Journal, 2015
    Co-Authors: Jiyong Zhang, Erin E Cummings, Grazyna B Sadowska, Oleksandr Makeyev, Xiaodi Chen, Seon Yeong Park, Jeong Eun Kim, Courtney A Bodge, Yow Pin Lim, Walter G. Besio
    Abstract:

    Impaired blood-Brain Barrier function represents an important component of hypoxic-ischemic Brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-Brain Barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-Brain Barrier abnormalities have not been examined in the immature Brain in vivo. We generated pharmacologic quantities of ovine-specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal sheep at 126 days of gestation after exposure to Brain ischemia. Anti-IL-6 mAbs were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid, blood-Brain Barrier permeability was quantified using the blood-to-Brain transfer constant in Brain regions, and IL-6, tight junction proteins, and plasmalemma vesicle protein (PLVAP) were detected by Western immunoblot. Anti-IL-6 mAb infusions resulted in increases in mAb (P < 0.05) in plasma, Brain parenchyma, and cerebrospinal fluid and decreases in Brain IL-6 protein. Twenty-four hours after ischemia, anti-IL-6 mAb infusions attenuated ischemia-related increases in blood-Brain Barrier permeability and modulated tight junction and PLVAP protein expression in fetal Brain. We conclude that inhibiting the effects of IL-6 protein with systemic infusions of neutralizing antibodies attenuates ischemia-related increases in blood-Brain Barrier permeability by inhibiting IL-6 and modulates tight junction proteins after ischemia.

  • ischemia reperfusion impairs blood Brain Barrier function and alters tight junction protein expression in the ovine fetus
    Neuroscience, 2012
    Co-Authors: Xiaodi Chen, Erin E Cummings, Ilona Juan, John N Gaitanis, Grazyna B Sadowska, Oleksandr Makeyev, Walter G. Besio, Steven W Threlkeld, William A Banks, Barbara S. Stonestreet
    Abstract:

    The blood-Brain Barrier is a restrictive interface between the Brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood-Brain Barrier. Hypoxic-ischemic damage to the blood-Brain Barrier could be an important component of fetal Brain injury. We hypothesized that increases in blood- Brain Barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impair- ment in blood-Brain Barrier function in the fetus. Blood- Brain Barrier function was quantified with the blood-to-Brain transfer constant (Ki) and tight junction proteins by Western immunoblot in fetal sheep at 127 days of gestation without ischemia, and 4, 24, or 48 h after ischemia. The largest increase in Ki (P < 0.05) was 4 h after ischemia. Occludin and claudin-5 expressions decreased at 4 h, but returned toward control levels 24 and 48 h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse corre- lations between Ki and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood-Brain Barrier function after ischemia. We conclude that impaired blood-Brain Barrier function is an important component of hypoxic-ischemic Brain injury in the fetus, and that increases in quantitatively measured Barrier permeability (K

Ferenc A Jolesz - One of the best experts on this subject based on the ideXlab platform.

  • noninvasive mr imaging guided focal opening of the blood Brain Barrier in rabbits
    Radiology, 2001
    Co-Authors: Kullervo Hynynen, Nathan Mcdannold, Natalia Vykhodtseva, Ferenc A Jolesz
    Abstract:

    PURPOSE: To determine if focused ultrasound beams can be used to locally open the blood-Brain Barrier without damage to surrounding Brain tissue and if magnetic resonance (MR) imaging can be used to monitor this procedure. MATERIALS AND METHODS: The Brains of 18 rabbits were sonicated (pulsed sonication) in four to six locations, with temporal peak acoustic power ranging from 0.2 to 11.5 W. Prior to each sonication, a bolus of ultrasonographic (US) contrast agent was injected into the ear vein of the rabbit. A series of fast or spoiled gradient-echo MR images were obtained during the sonications to monitor the temperature elevation and potential tissue changes. Contrast material-enhanced MR images obtained minutes after sonications and repeated 1-48 hours later were used to depict blood-Brain Barrier opening. Whole Brain histologic evaluation was performed. RESULTS: Opening of the blood-Brain Barrier was confirmed with detection of MR imaging contrast agent at the targeted locations. The lowest power levels used produced blood-Brain Barrier opening without damage to the surrounding neurons. Contrast enhancement correlated with the focal signal intensity changes in the magnitude fast spoiled gradient-echo MR images. CONCLUSION: The blood-Brain Barrier can be consistently opened with focused ultrasound exposures in the presence of a US contrast agent. MR imaging signal intensity changes may be useful in the detection of blood-Brain Barrier opening during sonication.

  • noninvasive mr imaging guided focal opening of the blood Brain Barrier in rabbits
    Radiology, 2001
    Co-Authors: Kullervo Hynynen, Nathan Mcdannold, Natalia Vykhodtseva, Ferenc A Jolesz
    Abstract:

    PURPOSE: To determine if focused ultrasound beams can be used to locally open the blood-Brain Barrier without damage to surrounding Brain tissue and if magnetic resonance (MR) imaging can be used to monitor this procedure. MATERIALS AND METHODS: The Brains of 18 rabbits were sonicated (pulsed sonication) in four to six locations, with temporal peak acoustic power ranging from 0.2 to 11.5 W. Prior to each sonication, a bolus of ultrasonographic (US) contrast agent was injected into the ear vein of the rabbit. A series of fast or spoiled gradient-echo MR images were obtained during the sonications to monitor the temperature elevation and potential tissue changes. Contrast material–enhanced MR images obtained minutes after sonications and repeated 1–48 hours later were used to depict blood-Brain Barrier opening. Whole Brain histologic evaluation was performed. RESULTS: Opening of the blood-Brain Barrier was confirmed with detection of MR imaging contrast agent at the targeted locations. The lowest power leve...

Walter H Backes - One of the best experts on this subject based on the ideXlab platform.

  • blood Brain Barrier dysfunction in small vessel disease related intracerebral hemorrhage
    Frontiers in Neurology, 2018
    Co-Authors: Whitney M Freeze, Heidi I L Jacobs, Floris H B M Schreuder, Robert J Van Oostenbrugge, Walter H Backes, Frans R J Verhey, Catharina J M Klijn
    Abstract:

    Background and Purpose: Hypertensive vasculopathy and cerebral amyloid angiopathy are the two most common forms of cerebral small vessel disease. Both forms are associated with the development of primary intracerebral hemorrhage, but the pathophysiological mechanisms underlying spontaneous vessel rupture remain unknown. This work constitutes a systematic review on blood-Brain Barrier dysfunction in the etiology of spontaneous intracerebral hemorrhage due to cerebral small vessel disease. Methods: We searched Medline (1946-2018) and Embase (1974-2018) for animal and human studies reporting on blood-Brain Barrier dysfunction associated with intracerebral hemorrhage or cerebral microbleeds. Results: Of 26 eligible studies, 10 were animal studies and 16 were in humans. The authors found indications for blood-Brain Barrier dysfunction in all four animal studies addressing hypertensive vasculopathy-related intracerebral hemorrhage (n = 32 hypertensive animals included in all four studies combined), and in four of six studies on cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 47). Of the studies in humans, five of six studies in patients with cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 117) and seven out of nine studies examining intracerebral hemorrhage with mixed or unspecified underlying etiology (n = 489) found indications for blood-Brain Barrier dysfunction. One post-mortem study in hypertensive vasculopathy-related intracerebral hemorrhage (n = 82) found no evidence for blood-Brain Barrier abnormalities. Conclusions: Signs of blood-Brain Barrier dysfunction were found in 20 out of 26 studies. Blood-Brain Barrier integrity deserves further investigation with a view to identification of potential treatment targets for spontaneous intracerebral hemorrhage.

  • blood Brain Barrier dysfunction in small vessel disease related intracerebral hemorrhage
    Frontiers in Neurology, 2018
    Co-Authors: Whitney M Freeze, Heidi I L Jacobs, Floris H B M Schreuder, Walter H Backes, Frans R J Verhey, Robert J Van Oostenbrugge, Catharina J M Klijn
    Abstract:

    Background and purpose: Hypertensive vasculopathy and cerebral amyloid angiopathy are the two most common forms of cerebral small vessel disease. Both forms are associated with the development of primary intracerebral hemorrhage, but the pathophysiological mechanisms underlying spontaneous vessel rupture remain unknown. This work constitutes a systematic review on blood-Brain Barrier dysfunction in the etiology of spontaneous intracerebral hemorrhage due to cerebral small vessel disease. Methods: We searched Medline (1946-2018) and Embase (1974-2018) for animal and human studies reporting on blood-Brain Barrier dysfunction associated with intracerebral hemorrhage or cerebral microbleeds. Results: Of twenty-six eligible studies, ten were animal studies and sixteen were in humans. The authors found indications for blood-Brain Barrier dysfunction in all four animal studies addressing hypertensive vasculopathy-related intracerebral hemorrhage (n=32 hypertensive animals included in all four studies combined), and in four of six studies on cerebral amyloid angiopathy-related intracerebral hemorrhage (n=47). Of the studies in humans, five of six studies in patients with cerebral amyloid angiopathy-related intracerebral hemorrhage (n=117) and seven out of nine studies examining intracerebral hemorrhage with mixed or unspecified underlying etiology (n=489) found indications for blood-Brain Barrier dysfunction. One post-mortem study in hypertensive vasculopathy-related intracerebral hemorrhage (n=82) found no evidence for blood-Brain Barrier abnormalities. Conclusions: Signs of blood-Brain Barrier dysfunction were found in twenty out of twenty-six studies. Blood-Brain Barrier integrity deserves further investigation with a view to identification of potential treatment targets for spontaneous intracerebral hemorrhage.

  • Image_1_Blood-Brain Barrier Dysfunction in Small Vessel Disease Related Intracerebral Hemorrhage.TIFF
    2018
    Co-Authors: Whitney M Freeze, Heidi I L Jacobs, Floris H B M Schreuder, Robert J Van Oostenbrugge, Walter H Backes, Frans R J Verhey, Catharina J M Klijn
    Abstract:

    Background and Purpose: Hypertensive vasculopathy and cerebral amyloid angiopathy are the two most common forms of cerebral small vessel disease. Both forms are associated with the development of primary intracerebral hemorrhage, but the pathophysiological mechanisms underlying spontaneous vessel rupture remain unknown. This work constitutes a systematic review on blood-Brain Barrier dysfunction in the etiology of spontaneous intracerebral hemorrhage due to cerebral small vessel disease.Methods: We searched Medline (1946–2018) and Embase (1974–2018) for animal and human studies reporting on blood-Brain Barrier dysfunction associated with intracerebral hemorrhage or cerebral microbleeds.Results: Of 26 eligible studies, 10 were animal studies and 16 were in humans. The authors found indications for blood-Brain Barrier dysfunction in all four animal studies addressing hypertensive vasculopathy-related intracerebral hemorrhage (n = 32 hypertensive animals included in all four studies combined), and in four of six studies on cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 47). Of the studies in humans, five of six studies in patients with cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 117) and seven out of nine studies examining intracerebral hemorrhage with mixed or unspecified underlying etiology (n = 489) found indications for blood-Brain Barrier dysfunction. One post-mortem study in hypertensive vasculopathy-related intracerebral hemorrhage (n = 82) found no evidence for blood-Brain Barrier abnormalities.Conclusions: Signs of blood-Brain Barrier dysfunction were found in 20 out of 26 studies. Blood-Brain Barrier integrity deserves further investigation with a view to identification of potential treatment targets for spontaneous intracerebral hemorrhage.

  • blood Brain Barrier leakage in patients with early alzheimer disease
    Radiology, 2016
    Co-Authors: Harm J Van De Haar, Frans R J Verhey, Saartje Burgmans, Jacobus F A Jansen, Matthias J P Van Osch, Mark A Van Buchem, Majon Muller, Paul A M Hofman, Walter H Backes
    Abstract:

    MR imaging was used to show global, diffusely distributed leakage of the blood-Brain Barrier in patients with early Alzheimer disease, which suggests that a compromised blood-Brain Barrier is part of the early pathology of Alzheimer disease and might be part of a cascade of pathologic events that eventually lead to cognitive decline.