scholarly journals Micro-computed tomography in murine models of cerebral cavernous malformations as a paradigm for brain disease

2016 ◽  
Vol 271 ◽  
pp. 14-24 ◽  
Author(s):  
Romuald Girard ◽  
Hussein A. Zeineddine ◽  
Courtney Orsbon ◽  
Huan Tan ◽  
Thomas Moore ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Brain Disease ◽  
Cerebral Cavernous Malformations ◽  
Murine Models ◽  
Micro Computed Tomography ◽  
Cavernous Malformations

scholarly journals B-Cell Depletion Reduces the Maturation of Cerebral Cavernous Malformations in Murine Models

2016 ◽  
Vol 11 (2) ◽  
pp. 369-377 ◽  
Author(s):  
Changbin Shi ◽  
Robert Shenkar ◽  
Hussein A. Zeineddine ◽  
Romuald Girard ◽  
Maged D. Fam ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Depletion ◽  
Cerebral Cavernous Malformations ◽  
B Cell Depletion ◽  
Murine Models ◽  
Cavernous Malformations

Abstract 126: Phenotypic Features of Murine Models of Cerebral Cavernous Malformations

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Hussein Zeineddine ◽  
Romuald Girard ◽  
Thomas Moore ◽  
Rhonda Lightle ◽  
Ying Cao ◽  
...  
Keyword(s):  
T Cells ◽  
Iron Deposition ◽  
Cerebral Cavernous Malformations ◽  
Murine Models ◽  
Lesion Area ◽  
Cavernous Malformations ◽  
Chronic Model ◽  
Chronic Models ◽  
Phenotypic Features ◽  
Rock Activity

Introduction: Cerebral cavernous malformations (CCM) are hemorrhagic lesions causing stroke and epilepsy. They develop with loss of function of three known genes in endothelial cells (ECs). Mice heterozygous for Ccm 1, 2 or 3 genes develop CCMs stochastically during life (“chronic models”), especially when bred in a background predisposing to somatic mutations ( p53 or Msh2 loss) . CCM lesions can also be generated in the developing hindbrain and retinas by Cre-recombinase induced homozygous loss of Ccm 1, 2, or 3 genes in the immediate postnatal period (“acute models”). We hypothesized that the CCM lesions which develop in the various models reflect different phenotypic features of the human disease. Methods: Eight murine models of CCM were used in this study and defined as being chronic ( Ccm1 +/- Msh2 -/- , Ccm3 +/- and Ccm3 +/- Trp53 -/- ) or acute ( Pdgfb iCreERT2 Ccm1 fl/fl , Pdgfb iCreERT2 Ccm3 fl/fl and Cdh5 CreERT2 Ccm1 fl/fl ). Volumetric lesion burden was assessed using micro-CT after adjusting for total brain volume. Other phenotypic markers were assessed including the prevalence of ECs with Rho-associated protein kinase (ROCK) activity, and quantitation of B and T cells infiltration and non-heme iron deposition in the CCM lesions. Results: The acute neonatal models showed higher adjusted volume lesion burden than the paired chronic model (p=0.013). CCM EC ROCK activity was similar in the acute and chronic models. Background brain EC ROCK activity in chronic models was higher than that in acute model (p=0.012). CCM lesions in chronic models (16 lesions/13 mice) had higher integrated iron intensity per lesion area compared to the acute lesions (12 lesions/9 mice) (p=0.03). Chronic lesions had a higher number of B cells (p=0.005), more T cells (p=0.04) per lesion area, and more combined lymphocytes (p=0.002) per lesion area compared to the acute model. Conclusion: The acute model harbored a significantly higher lesion burden making them suitable for studying lesion genesis mechanisms. The chronic model however is more suited to study the role of inflammation and iron deposition in CCM, hallmark features of clinically relevant CCM lesions in man.

scholarly journals Thrombospondin1 (TSP1) replacement prevents cerebral cavernous malformations

2017 ◽  
Vol 214 (11) ◽  
pp. 3331-3346 ◽  
Author(s):  
Miguel Alejandro Lopez-Ramirez ◽  
Gregory Fonseca ◽  
Hussein A. Zeineddine ◽  
Romuald Girard ◽  
Thomas Moore ◽  
...  
Keyword(s):  
Cavernous Malformation ◽  
Angiogenesis Inhibitors ◽  
Cerebral Cavernous Malformations ◽  
Growth Factor Signaling ◽  
Vascular Endothelial ◽  
Micro Computed Tomography ◽  
Cavernous Malformations ◽  
In Vitro Reconstitution ◽  
Endothelial Growth Factor

KRIT1 mutations are the most common cause of cerebral cavernous malformation (CCM). Acute Krit1 gene inactivation in mouse brain microvascular endothelial cells (BMECs) changes expression of multiple genes involved in vascular development. These changes include suppression of Thbs1, which encodes thrombospondin1 (TSP1) and has been ascribed to KLF2- and KLF4-mediated repression of Thbs1. In vitro reconstitution of TSP1 with either full-length TSP1 or 3TSR, an anti-angiogenic TSP1 fragment, suppresses heightened vascular endothelial growth factor signaling and preserves BMEC tight junctions. Furthermore, administration of 3TSR prevents the development of lesions in a mouse model of CCM1 (Krit1ECKO) as judged by histology and quantitative micro-computed tomography. Conversely, reduced TSP1 expression contributes to the pathogenesis of CCM, because inactivation of one or two copies of Thbs1 exacerbated CCM formation. Thus, loss of Krit1 function disables an angiogenic checkpoint to enable CCM formation. These results suggest that 3TSR, or other angiogenesis inhibitors, can be repurposed for TSP1 replacement therapy for CCMs.

scholarly journals Phenotypic characterization of murine models of cerebral cavernous malformations

2018 ◽  
Vol 99 (3) ◽  
pp. 319-330 ◽  
Author(s):  
Hussein A. Zeineddine ◽  
Romuald Girard ◽  
Laleh Saadat ◽  
Le Shen ◽  
Rhonda Lightle ◽  
...  
Keyword(s):  
Phenotypic Characterization ◽  
Cerebral Cavernous Malformations ◽  
Murine Models ◽  
Cavernous Malformations

scholarly journals Novel Murine Models of Cerebral Cavernous Malformations

Angiogenesis ◽  
2020 ◽  
Vol 23 (4) ◽  
pp. 651-666
Author(s):  
Matthew R. Detter ◽  
Robert Shenkar ◽  
Christian R. Benavides ◽  
Catherine A. Neilson ◽  
Thomas Moore ◽  
...  
Keyword(s):  
Cerebral Cavernous Malformations ◽  
Murine Models ◽  
Cavernous Malformations

scholarly journals RhoA Kinase Inhibition With Fasudil Versus Simvastatin in Murine Models of Cerebral Cavernous Malformations

Stroke ◽  
2017 ◽  
Vol 48 (1) ◽  
pp. 187-194 ◽  
Author(s):  
Robert Shenkar ◽  
Changbin Shi ◽  
Cecilia Austin ◽  
Thomas Moore ◽  
Rhonda Lightle ◽  
...  
Keyword(s):  
Cerebral Cavernous Malformations ◽  
Murine Models ◽  
Kinase Inhibition ◽  
Cavernous Malformations ◽  
Rhoa Kinase

Cortical and trabecular bone parameters from HR-Pqct images at the Tibia: a local comparison with synchrotron radiation micro-computed tomography

2013 ◽  
Author(s):  
Agnes Ostertag ◽  
Francoise Peyrin ◽  
Sylvie Fernandez ◽  
Jean-Denis Laredo ◽  
Vernejoul Marie-Christine De ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Synchrotron Radiation ◽  
Trabecular Bone ◽  
Micro Computed Tomography ◽  
Bone Parameters ◽  
Local Comparison

Morphology and Affinities of Ampelocissites Seeds (Vitaceae: Ampelopsis clade) from the Paleogene of Texas, USA

2020 ◽  
Vol 45 (3) ◽  
pp. 478-482
Author(s):  
Steven R. Manchester
Keyword(s):  
Computed Tomography ◽  
Cross Sections ◽  
Seed Coat ◽  
Ct Scanning ◽  
Seed Morphology ◽  
Early Eocene ◽  
Micro Computed Tomography ◽  
X Ray ◽  
Fossil Seeds ◽  
Fossil Genus

Abstract—The type material on which the fossil genus name Ampelocissites was established in 1929 has been reexamined with the aid of X-ray micro-computed tomography (μ-CT) scanning and compared with seeds of extant taxa to assess the relationships of these fossils within the grape family, Vitaceae. The specimens were collected from a sandstone of late Paleocene or early Eocene age. Although originally inferred by Berry to be intermediate in morphology between Ampelocissus and Vitis, the newly revealed details of seed morphology indicate that these seeds represent instead the Ampelopsis clade. Digital cross sections show that the seed coat maintains its thickness over the external surfaces, but diminishes quickly in the ventral infolds. This feature, along with the elliptical chalaza and lack of an apical groove, indicate that Ampelocissites lytlensis Berry probably represents Ampelopsis or Nekemias (rather than Ampelocissus or Vitis) and that the generic name Ampelocissites may be useful for fossil seeds with morphology consistent with the Ampelopsis clade that lack sufficient characters to specify placement within one of these extant genera.

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