Branch order regression for modeling brain vasculature

2018 ◽  
Vol 45 (3) ◽  
pp. 1123-1134 ◽  
Author(s):  
Kingshuk Roy Choudhury ◽  
Sean Skwerer
Keyword(s):  
Branch Order ◽  
Brain Vasculature

Periodontal Pathogens and Neuropsychiatric Health

2020 ◽  
Vol 20 (15) ◽  
pp. 1353-1397 ◽  
Author(s):  
Abhishek Wadhawan ◽  
Mark A. Reynolds ◽  
Hina Makkar ◽  
Alison J. Scott ◽  
Eileen Potocki ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Low Grade ◽  
Periodontal Pathogens ◽  
Synergistic Interactions ◽  
Brain Vasculature ◽  
Micro Rnas ◽  
Clinical Conditions ◽  
Low Grade Inflammation ◽  
Neuropsychiatric Illness

Increasing evidence incriminates low-grade inflammation in cardiovascular, metabolic diseases, and neuropsychiatric clinical conditions, all important causes of morbidity and mortality. One of the upstream and modifiable precipitants and perpetrators of inflammation is chronic periodontitis, a polymicrobial infection with Porphyromonas gingivalis (P. gingivalis) playing a central role in the disease pathogenesis. We review the association between P. gingivalis and cardiovascular, metabolic, and neuropsychiatric illness, and the molecular mechanisms potentially implicated in immune upregulation as well as downregulation induced by the pathogen. In addition to inflammation, translocation of the pathogens to the coronary and peripheral arteries, including brain vasculature, and gut and liver vasculature has important pathophysiological consequences. Distant effects via translocation rely on virulence factors of P. gingivalis such as gingipains, on its synergistic interactions with other pathogens, and on its capability to manipulate the immune system via several mechanisms, including its capacity to induce production of immune-downregulating micro-RNAs. Possible targets for intervention and drug development to manage distal consequences of infection with P. gingivalis are also reviewed.

scholarly journals Differential responses of needle and branch order-based root decay to nitrogen addition: dominant effects of acid-unhydrolyzable residue and microbial enzymes

2015 ◽  
Vol 394 (1-2) ◽  
pp. 315-327 ◽  
Author(s):  
Liang Kou ◽  
Weiwei Chen ◽  
Xinyu Zhang ◽  
Wenlong Gao ◽  
Hao Yang ◽  
...  
Keyword(s):  
Nitrogen Addition ◽  
Microbial Enzymes ◽  
Branch Order ◽  
Root Decay ◽  
Differential Responses

scholarly journals Crawling Phagocytes Recruited in the Brain Vasculature after Pertussis Toxin Exposure through IL6, ICAM1 and ITGαM

2011 ◽  
Vol 21 (6) ◽  
pp. 661-671 ◽  
Author(s):  
Jean-François Richard ◽  
Monica Roy ◽  
Julie Audoy-Rémus ◽  
Pierrot Tremblay ◽  
Luc Vallières
Keyword(s):  
Pertussis Toxin ◽  
Brain Vasculature ◽  
Toxin Exposure ◽  
The Brain

Abstract MP17: Upregulating E2F1 Mitigates Senescence-Associated Phenotypes in Cultured Primary Endothelial Cells

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Michael E Maniskas ◽  
Yun-ju Lai ◽  
Sean P Marrelli ◽  
Louise D McCullough ◽  
Jose F Moruno-manchon
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Neurovascular Unit ◽  
Glucose Deprivation ◽  
Cerebral Hypoperfusion ◽  
Aged Mouse ◽  
Aged Mice ◽  
Brain Vasculature ◽  
Bilateral Carotid ◽  
The Brain

Vascular contributions to cognitive impairment and dementia (VCID) includes multiple disorders that are identified by cognitive deficits secondary to cerebrovascular pathology. The risk of VCID is higher in people after the age of 70, and, currently, there is no effective treatment. Vascular endothelial cells (VEC) are critical components of the brain vasculature and neurovascular unit and their health is vital to the capacity of the brain vasculature to respond to stressors. However, aged VEC may enter an irreversible replicative-arrest state (senescence), which has been associated with dementia. E2F transcription factor 1 (E2F1) regulates cell cycle progression and DNA damage repair. Importantly, E2F1 deficiency is associated with cell senescence. We hypothesized that E2F1 downregulation contributes to senescence in the cerebral endothelium during aging. We used cultured primary VEC from young (4-months old, mo) and aged (18-mo) male and female mice for RNA sequencing, plasmid-based gene delivery, high-resolution microscopy, and (4-, 12-, and 18-mo) mice of the bilateral carotid artery stenosis (BCAS) model, which produces chronic cerebral hypoperfusion and recapitulates some of the features seen in patients with VCID. We found that overexpression of E2F1 reduced the levels of senescence-associated phenotypes in cultured VEC from young mice that were exposed to oxygen and glucose deprivation (p<0.001), which induces endothelial senescence. Our RNA seq data showed that the expression of E2f1 was reduced (~40%) in cultured primary VEC from aged mouse brains compared with young cells (p<0.001). E2F1 levels were reduced in the brains of aged mice. Interestingly, we found sex differences in E2F1 levels, with less protein levels (~30%) in males vs females (p<0.05), independently of age. Also, aged BCAS mice (1 month after surgery) had more severe senescence phenotypes, reduced cerebral blood flow, and worse memory deficits compared with control mice (p<0.05). The effect of BCAS was more prominent in aged mice compared with younger (4- and 12-mo) mice. In conclusion , our study identifies E2F1 as a potential regulator of endothelial senescence in mice and highlights the contribution of aging as an important factor in losing endothelial resilience.

scholarly journals Skeletal muscle arteriolar function following myocardial infarction: Analysis of branch-order effects

2011 ◽  
Vol 81 (3) ◽  
pp. 337-343 ◽  
Author(s):  
Michael A. Tevald ◽  
John D. Lowman ◽  
Roland N. Pittman
Keyword(s):  
Myocardial Infarction ◽  
Skeletal Muscle ◽  
Order Effects ◽  
Branch Order

scholarly journals Using zebrafish to elucidate glial-vascular interactions during CNS development

2021 ◽  
Author(s):  
Robyn A. Umans ◽  
Carolyn Pollock ◽  
William A. Mills ◽  
Harald Sontheimer
Keyword(s):  
Blood Vessels ◽  
Cell Types ◽  
Transgenic Zebrafish ◽  
Suitable Model ◽  
Developmental Studies ◽  
Brain Vessels ◽  
Brain Vasculature ◽  
Area Of Interest ◽  
Vessel Development

AbstractAn emerging area of interest in Neuroscience is the cellular relationship between glia and blood vessels, as many of the presumptive support roles of glia require an association with the vasculature. These interactions are best studied in vivo and great strides have been made using mice to longitudinally image glial-vascular interactions. However, these methods are cumbersome for developmental studies, which could benefit from a more accessible system. Zebrafish (Danio rerio) are genetically tractable vertebrates, and given their translucency, are readily amenable for daily live imaging studies. We set out to examine whether zebrafish glia have conserved traits with mammalian glia regarding their ability to interact with and maintain the developing brain vasculature. We utilized transgenic zebrafish strains in which oligodendrocyte transcription factor 2 (olig2) and glial fibrillary acidic protein (gfap) identify different glial populations in the zebrafish brain and document their corresponding relationship with brain blood vessels. Our results demonstrate that olig2 and gfap zebrafish glia have distinct lineages and each interact with brain vessels as previously observed in mouse brain. Additionally, we manipulated these relationships through pharmacological and genetic approaches to distinguish the roles of these cell types during blood vessel development. olig2 glia use blood vessels as a pathway during their migration and Wnt signaling inhibition decreases their single-cell vessel co-option. By contrast, the ablation of gfap glia at the beginning of CNS angiogenesis impairs vessel development through a reduction in Vascular endothelial growth factor (Vegf), supporting a role for gfap glia during new brain vessel formation in zebrafish. This data suggests that zebrafish glia, akin to mammalian glia, have different lineages that show diverse interactions with blood vessels, and are a suitable model for elucidating glial-vascular relationships during vertebrate brain development.

scholarly journals Characterization and tissue localization of zebrafish homologs of the human ABCB1 multidrug transporter

2021 ◽  
Author(s):  
Robert W. Robey ◽  
Andrea N. Robinson ◽  
Fatima Ali-Rahmani ◽  
Lyn M. Huff ◽  
Sabrina Lusvarghi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Multidrug Transporter ◽  
Glycoprotein P ◽  
Tissue Localization ◽  
Brain Vasculature ◽  
P Glycoprotein ◽  
Capillary Endothelial Cells ◽  
The Brain ◽  
Viable Model

ABSTRACTGiven its similarities with mammalian systems, the zebrafish has emerged as a potential model to study the blood-brain barrier (BBB). Capillary endothelial cells at the human BBB express high levels of P-glycoprotein (P-gp, encoded by the ABCB1 gene) and ABCG2 (encoded by the ABCG2 gene). However, little information has been available about ATP-binding cassette transporters expressed at the zebrafish BBB. In this study, we focus on the characterization and tissue localization of two genes that are similar to human ABCB1, zebrafish abcb4 and abcb5. Cytotoxicity assays with stably-transfected cell lines revealed that zebrafish Abcb5 cannot efficiently transport the substrates doxorubicin and mitoxantrone compared to human P-gp and zebrafish Abcb4. Additionally, zebrafish Abcb5 did not transport the fluorescent probes BODIPY-ethylenediamine or LDS 751, while they were readily transported by Abcb4 and P-gp. A high-throughput screen conducted with 90 human P-gp substrates confirmed that zebrafish Abcb4 has overlapping substrate specificity with P-gp. Basal ATPase activity of zebrafish Abcb4 and Abcb5 was comparable to that of human P-gp. In the brain vasculature, RNAscope probes to detect abcb4 colocalized with staining by the P-gp antibody C219, while abcb5 was not detected. Zebrafish abcb4 also colocalized with claudin-5 expression in brain endothelial cells. Abcb4 and Abcb5 had different tissue localizations in multiple zebrafish tissues, consistent with different functions. The data suggest that zebrafish Abcb4 most closely phenocopies P-gp and that the zebrafish may be a viable model to study the role of the multidrug transporter P-gp at the BBB.

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