scholarly journals The role of vascular injury within the conditions of choline deficiency in rats with scopolamine-induced alzheimer's type dementia

Morphologia ◽  
2021 ◽  
Vol 15 (3) ◽  
pp. 66-75
Author(s):  
G.I. Gubina-Vakulik ◽  
Y.M. Zorenko

Background. The relationship between choline deficiency and vascular dysfunction continues to be relevant in the study of Alzheimer's disease. Objective. To study the morphological characteristics of vascular injury within the conditions of choline deficiency in rats with scopolamine-induced Alzheimer's type dementia. Methods. The experiment was performed on 48 WAG population male rats weighing 180-230 gr. Rats from groups Scop-14, Scop-14-SC, Scop-28, Scop-28-SC were injected intraperitoneally with scopolamine (Scop) butylbromide at a dosage of 1 mg/kg of body mass during 14 and 28 days and intravenously with mesenchymal stem cells (SC) at a single dosage of 500000 cells per 1 rat. Control animals (gr.C) were injected with 0.9% sodium chloride. Brain slides were stained with Congo-red and gallocyanine-chromium alum according to Einarson's method for total nucleic acids. The VEGF, E-cadherin expression was immunohistochemically determined in the brain cells cytoplasm. Results. The congophilic staining of the arteries walls, a decrease in endothelial cells with low the E-cadherin expression and an increase in the number of pericytes in the capillary wall was observed in the experimental groups. In gr.Scop-28 VEGF expression in endothelial cells, hippocampal neurons was greater than in gr.Scop-14. It indicated more intensive activation of angiogenesis and acetylcholine synthesis with correspondingly more pronounced vascular damage and choline deficiency. The cytoplasm of cortical neurons was diffusely labeled with VEGF antibodies in response to hypoxia, but the level of expression was almost no different from that in gr.C. In all groups, the optical density of the neuropile of the large hemispheres according to Einarson’s staining was reduced, i.e., the level of RNA in the neuronal processes was reduced. The introduction of stem cells restored the capillary wall due to young endothelial cells, reduced the VEFG synthesis in all studied cells and increased the RNA content in neuronal processes. Conclusion. The relationship between choline deficiency, neuronal process loss and vascular damage has been found. The blood vessels self-repair was occurred by substitution, after the stem cells introduction - by restitution.

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1168-1177 ◽  
Author(s):  
Minetaro Ogawa ◽  
Masami Kizumoto ◽  
Satomi Nishikawa ◽  
Tetsuhiro Fujimoto ◽  
Hiroaki Kodama ◽  
...  

Abstract Embryonic stem cells can differentiate in vitro into hematopoietic cells through two intermediate stages; the first being FLK1+ E-cadherin− proximal lateral mesoderm and the second being CD45− VE-cadherin+endothelial cells. To further dissect the CD45−VE-cadherin+ cells, we have examined distribution of 4-integrin on this cell population, because 4-integrin is the molecule expressed on hematopoietic stem cells. During culture of FLK1+ E-cadherin− cells, CD45− VE-cadherin+4-integrin− cells differentiate first, followed by 4-integrin+ cells appearing in both CD45− VE-cadherin+ and CD45−VE-cadherin− cell populations. In the CD45−VE-cadherin+ cell population, 4-integrin+ subset but not 4-integrin− subset had the potential to differentiate to hematopoietic lineage cells, whereas endothelial cell progenitors were present in both subsets. The CD45−VE-cadherin− 4-integrin+ cells also showed hematopoietic potential. Reverse transcription-polymerase chain reaction analyses showed that differential expression of the Gata2 and Myb genes correlated with the potential of the 4-integrin+ cells to give rise to hematopoietic cell differentiation. Hematopoietic CD45−VE-cadherin+ 4-integrin+ cells were also present in the yolk sac and embryonic body proper of 9.5 day postcoitum mouse embryos. Our results suggest that the expression of 4-integrin is a marker of the earliest precursor of hematopoietic cell lineage that was diverged from endothelial progenitors.


Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1168-1177 ◽  
Author(s):  
Minetaro Ogawa ◽  
Masami Kizumoto ◽  
Satomi Nishikawa ◽  
Tetsuhiro Fujimoto ◽  
Hiroaki Kodama ◽  
...  

Embryonic stem cells can differentiate in vitro into hematopoietic cells through two intermediate stages; the first being FLK1+ E-cadherin− proximal lateral mesoderm and the second being CD45− VE-cadherin+endothelial cells. To further dissect the CD45−VE-cadherin+ cells, we have examined distribution of 4-integrin on this cell population, because 4-integrin is the molecule expressed on hematopoietic stem cells. During culture of FLK1+ E-cadherin− cells, CD45− VE-cadherin+4-integrin− cells differentiate first, followed by 4-integrin+ cells appearing in both CD45− VE-cadherin+ and CD45−VE-cadherin− cell populations. In the CD45−VE-cadherin+ cell population, 4-integrin+ subset but not 4-integrin− subset had the potential to differentiate to hematopoietic lineage cells, whereas endothelial cell progenitors were present in both subsets. The CD45−VE-cadherin− 4-integrin+ cells also showed hematopoietic potential. Reverse transcription-polymerase chain reaction analyses showed that differential expression of the Gata2 and Myb genes correlated with the potential of the 4-integrin+ cells to give rise to hematopoietic cell differentiation. Hematopoietic CD45−VE-cadherin+ 4-integrin+ cells were also present in the yolk sac and embryonic body proper of 9.5 day postcoitum mouse embryos. Our results suggest that the expression of 4-integrin is a marker of the earliest precursor of hematopoietic cell lineage that was diverged from endothelial progenitors.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Natália Ruggeri Barbaro ◽  
Thiago Matos de Araújo ◽  
José Eduardo Tanus-Santos ◽  
Gabriel Forato Anhê ◽  
Vanessa Fontana ◽  
...  

Inflammatory cytokines have been associated with the pathophysiology of hypertension and target organ damage (TOD). Resistant hypertensive patients (RHTN) are characterized by poor blood pressure control and higher prevalence of TOD. This study evaluated the relationship between plasma levels of TNF-αand arterial stiffness (pulse wave velocity—PWV) in 32 RHTN and 19 normotensive subjects. Moreover, we investigated the effect of TNF-αinhibition on human endothelial cells (HUVECs) incubated with serum from RHTN and normotensive subjects. HUVECs containing serum obtained from normotensiven=8and hypertensiven=8individuals were treated with TNF-αinhibitor (infliximab). Cell suspensions were used for measurement of DNA fragmentation and reactive oxygen species (ROS) content. RHTN patients showed higher levels of TNF-αcompared to normotensive subjects, as well as higher PWV. Positive correlation was found between TNF-αlevels and PWV measures in the whole group. HUVECs incubated with serum from RHTN showed increased cell apoptosis and higher ROS content compared to normotensive subjects. Infliximab attenuated the apoptosis of HUVECs incubated with serum from RHTN, but no effect in ROS production was observed. Our findings suggest that TNF-αmight mediate, at least in part, vascular damage in resistant hypertension.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Chao Hung Wang ◽  
Wen-Jin Cherng ◽  
I-Chang Hsieh ◽  
Ning-I Yang ◽  
Chi-Hsiao Yeh

Objectives: Mesenchymal stem cells (MSCs) from the bone marrow (BM) are pluripotent and have the capacity to differentiate into cardiomyocytes, endothelial cells (ECs), and smooth muscle cells (SMCs). Currently, MSCs are one of a number of cell types undergoing extensive investigation for cardiac regeneration therapy. However, it has not yet been determined whether this cell therapy also substantially contributes to vascular remodeling of diseased vessels, such as in intimal hyperplasia. Methods and Results: Human MSCs and a variety of progenitor and vascular cells were used for in vitro and in vivo adhesion experiments. To test the contribution of MSCs to intimal hyperplasia, MSCs from eGFP mice were injected via the tail vein of wild-type littermates after femoral artery wire injury. A model of direct BM transplantation of eGFP MSCs into the tibias of irradiated wild-type littermates was also conducted. Wire-induced vascular injury mobilized MSCs into the circulation. Compared to human aortic SMCs, MSCs exhibited a 2.8-fold increase in the adhesion capacity in vitro ( p < 0.001), and a 6.3-fold increase in vivo ( p < 0.001). In all animal models, immunostaining showed that a significant amount of eGFP MSCs contributed to intimal hyperplasia after vascular injury. Furthermore, MSCs were able to differentiate into cells of endothelial or smooth muscle lineage on the injured vessel wall. Co-culture experiments demonstrated that late-outgrowth ECs guided MSCs to differentiate towards an endothelial lineage through a paracrine effects rather than direct cell-cell interactions. In vivo , cell therapy with late-outgrowth ECs significantly attenuated the thickness of the neointima contributed by MSCs (intima/media ratio, from 3.2 ± 0.4 to 0.4 ± 0.1, p < 0.001). Conclusions: This study raises concerns about the detrimental effects of stem cell therapy on injured vessel remodeling. Tissue regeneration therapy with MSCs or cell populations containing MSCs requires a strategy to attenuate the high potential of MSCs to develop intimal hyperplasia on diseased vessels.


2008 ◽  
Vol 28 (1) ◽  
pp. 54-60 ◽  
Author(s):  
Chao-Hung Wang ◽  
Wen-Jin Cherng ◽  
Ning-I Yang ◽  
Li-Tang Kuo ◽  
Chia-Ming Hsu ◽  
...  

1991 ◽  
Vol 65 (04) ◽  
pp. 364-368 ◽  
Author(s):  
Hideo Wada ◽  
Shigehisa Tamaki ◽  
Motoaki Tanigawa ◽  
Mikio Takagi ◽  
Yoshitaka Mori ◽  
...  

SummaryThe plasma level of interleukin-1β (IL-1β) was determined in normal individuals, patients with disseminated intravascular coagulation (DIC), patients in the pre-DIC period (within 7 days before the onset of DIC), and non-DIC patients to examine the relationship between DIC and the plasma ILlp level. The plasma IL-1β level was 0-0.085 ng/ml in normal individuals, with little difference being seen according to related age. It was significantly higher in the DIC group (0.19 ± 0.19 ng/ml) than in the pre-DIC group (0.05 ± 0.08 ng/ml) or the non-DIC group (0.09 ± 0.01 ng/ml). The plasma IL-1β level was not markedly elevated in leukemia patients, even in the DIC group, but it was significantly increased in the DIC group of solid cancer patients and was generally elevated in patients with sepsis. It was markedly elevated to 0.39 ± 0.26 ng/ml in patients with organ failure. When mononuclear cells were incubated with lipopolysaccharide, it was found that IL-1β, tumor necrosis factor, and tissue factor (TF) were released into the medium, and there was an increase of TF release from endothelial cells incubated with this medium. These results suggest that the increase in IL-Iβ reflected the activation of monocytes and may be an important factor in DIC and its associated organ failure.


2017 ◽  
Vol 68 (6) ◽  
pp. 1341-1344
Author(s):  
Grigore Berea ◽  
Gheorghe Gh. Balan ◽  
Vasile Sandru ◽  
Paul Dan Sirbu

Complex interactions between stem cells, vascular cells and fibroblasts represent the substrate of building microenvironment-embedded 3D structures that can be grafted or added to bone substitute scaffolds in tissue engineering or clinical bone repair. Human Adipose-derived Stem Cells (hASCs), human umbilical vein endothelial cells (HUVECs) and normal dermal human fibroblasts (NDHF) can be mixed together in three dimensional scaffold free constructs and their behaviour will emphasize their potential use as seeding points in bone tissue engineering. Various combinations of the aforementioned cell lines were compared to single cell line culture in terms of size, viability and cell proliferation. At 5 weeks, viability dropped for single cell line spheroids while addition of NDHF to hASC maintained the viability at the same level at 5 weeks Fibroblasts addition to the 3D construct of stem cells and endothelial cells improves viability and reduces proliferation as a marker of cell differentiation toward osteogenic line.


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