Abstract WMP82: Exosomes Derived From Cerebral Endothelial Cells of Young Adult Rats Reduced Cognitive Deficits in Aged Diabetic Rats

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Li Zhang ◽  
Michael Chopp ◽  
Chao Li ◽  
Quan Jiang ◽  
Guang Liang Ding ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cognitive Function ◽  
Young Adult ◽  
Cognitive Decline ◽  
Brain Slices ◽  
Amyloid Β ◽  
Adult Rats ◽  
Glymphatic System ◽  
Cerebral Endothelial Cells

Introduction: Diabetes mellitus (DM) is associated with cognitive decline and dementia in the elderly. The glymphatic system mediates clearance of the interstitial solutes in the brain by exchange of cerebrospinal and interstitial fluid (CSF and ISF). We recently demonstrated that DM in aged rat induces impairment of the glymphatic system and cognitive decline. Exosomes, membrane vesicles, mediate intercellular communication by transferring their cargo into recipient cells. The present study investigated whether cerebral endothelial exosomes (CEE) ameliorate glymphatic system impairment and improve cognitive function in aged DM rats. Methods and Results: DM was induced in male Wistar rats (13 months, n=48) by injection of nicotinamide and streptozotocin. Two months after DM, rats were treated with CEE (1x10 11 exosomes/rat, IV) twice a week for 4 weeks. Age matched DM and non-DM rats were used as controls. CEE were harvested from the cultured cerebral endothelial cells of health young adult rats. Exchanges of CSF and ISF were measured by intracisternal injection of fluorescent tracer, Texas Red-dextran (TR, 3kD). Confocal microscopic analysis of brain slices revealed a progressive slowdown of ISF clearance in the hippocampi, assessed by retention of TR starting at 2.5 fold at 2M (13±5 vs 5±3% of area) and increasing to 4 fold at 4M (21±4 vs 5±2%) of DM. Paravascular amyloid β (Aβ) accumulation was only detected at 4M of DM. The CEE treatment significantly (p<0.05) reduced TR retention (10±4%) at 4M of DM and also decreased Aβ accumulation (2±1 vs 6±2/mm 2 ) and parenchymal fibrin deposition (9±5 vs 23±5/mm 2 ) compared to untreated DM rats. Moreover, the CEE treatment significantly improved hippocampal related learning and memory measured by the Morris Water Maze and odor-based novelty recognition for olfactory memory, without altering the glucose level. In vitro, cerebral endothelial cells isolated from 2M DM rats exhibited substantial dysfunction as measured by capillary-like tube formation and cell migration, whereas incubation with the CEE substantially reversed endothelial dysfunction. Conclusions: The CEE treatment reduces DM-induced glymphatic and cerebral endothelial dysfunctions, leading to improvement of cognitive function in aged DM rats.

Abstract P725: Cerebral Endothelial Cell Derived Exosomes Promote Neurogenesis and Improve Cognitive Function in Aged Diabetic Rats

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Li Zhang ◽  
Chao Li ◽  
Chunyang Wang ◽  
Rui Huang ◽  
Michael Chopp ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cognitive Function ◽  
Type Ii Diabetes Mellitus ◽  
Diabetic Rats ◽  
Hippocampal Neurogenesis ◽  
Adult Rats ◽  
Odor Recognition ◽  
Cerebral Endothelial Cells ◽  
The Social ◽  
Interaction Test

Introduction: Middle age and elderly patients with type II diabetes mellitus (DM) are at high risk to develop cognitive decline and dementia. Reduction of hippocampal neurogenesis is highly associated with impairment of cognitive function. Exosomes are small extracellular vesicles that play an important role in intercelluar communication by transferring proteins, lipids, and genomic materials including microRNAs between cells. In the present study, we tested the hypothesis that exosomes derived from healthy cerebral endothelial cells promote hippocampal neurogenesis and ameliorate cognitive impairment in aged DM rats. Methods: DM was induced in middle aged rats (13 month) by co-administration of nicotinamide and streptozotocin (NTM-STZ). Two months (2M) after NTM-STZ injection, rats with confirmed hyperglycemia were treated with exosomes derived from cerebral endothelial cells of healthy young-adult rats (CEC-Exo, 1x10 11 particles, IV, n=10) or saline (n=10), twice a week for 8 consecutive weeks. Bromodeoxyuridine (BrdU, IP) was administered daily for 7 days starting at 2M after NTM-STZ injection. Results: Compared with DM rats treated with saline, treatment of DM rats with CEC-Exo significantly (p<0.05) improved cognitive functions measured by Morris water maze (47±4% vs 40±5% of time spent in the correct quadrant), odor recognition test (56±6% vs 48±7% time spent on new odor), and the social interaction test (67±9% vs 54±14% interaction time with new rat). In addition, CEC-Exo robustly increased number of BrdU + cells by 60% and DCX + cells by 45% in the subgranular zone of the dentate gyrus compared with saline. Moreover, DCX + cells significantly increased their branch numbers by 54% and lengths by 51% in DM rats treated with CEC-Exo, suggesting that CEC-Exo promote DCX + neuroblasts maturation. Concurrently, CEC-Exo treatment significantly reduced numbers of vessels with fibrin deposition (8±3/mm 2 vs 18±7/mm 2 in saline) and extravascular leakage (3±2/mm 2 vs 7±3/mm 2 in saline) in the hippocampus. Conclusion: Treatment with CEC-Exo improves cognitive function in aged DM rats and augments neurogenesis and reduction of vascular thrombosis in the hippocampus, which in concert likely contribute the therapeutic effect of CEC-Exo.

Histochemical Studies On The In Vitro 5-HT Uptake In Endothelial Cells

1981 ◽  
Author(s):  
T Kjellström ◽  
H Ahlman ◽  
F Dahlström ◽  
G Hansson ◽  
B Stenberg ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Endothelial Cells ◽  
Factor Viii ◽  
Serotonin Uptake ◽  
Adult Rats ◽  
Pulmonary Endothelial Cells ◽  
Transmission Electron ◽  
5 Ht Uptake

Previous studies have shown that 5-HT is rapidly taken up by the endothelial cells and some investigations also suggested that serotonin is metabolized within these cells. In earlier studies on rat-lungs using a fluorescence histo- chemical method according to Hillarp - Falk we demonstrated that 5-HT was accumulated within the mast cells. Using this technique we could not demonstrate any specific uptake in the pulmonary endothelial cells. It was the purpose of the present investigation to further study the 5-HT uptake by isolated pulmonary endothelial cells.Methods Cells from the vascular intima of the pulmonary artery in adult rats were grown in a growth medium containing FCS. The endothelial nature of these cells was demonstrated using transmission electron microscopy and factor VIII analysis. Confluent endothelial cells were incubated with 5-HT and the cellular uptake was studied with fluorescence microscopy according to the Hillarp - Falk procedure.Results The endothelial cells were identified by the presence of Weibel-Palade bodies using transmission electron microscopy and the immunofluorescent demonstration of cellular factor VIII antigen. Cells not exposed to serotonin had no specific 5-HT fluorescense. After incubation with 5-HT at different concentrations there was a progressive uptake of the amine within the cells.Conclusions This study confirms previous reports on the specific serotonin uptake in endothelial cells. The Hillarp-Falk procedure seems suitable for further studies of serotonin uptake in cultured endothelial cells.

scholarly journals The Synthesis and Release of Insulin in Fetal, Nursing and Young Adult Rats: Studies in Vivo and in Vitro

1975 ◽  
Vol 9 (1) ◽  
pp. 17-25
Author(s):  
Enrique Blázquez ◽  
Leon A Lipshaw ◽  
Mercedes Blázquez ◽  
Piero P Foa
Keyword(s):  
Young Adult ◽  
Adult Rats

Adrenomedullin protects rat cerebral endothelial cells from oxidant damage in vitro

2005 ◽  
Vol 130 (1-2) ◽  
pp. 27-34 ◽  
Author(s):  
Lei Chen ◽  
Bela Kis ◽  
David W. Busija ◽  
Hiroshi Yamashita ◽  
Yoichi Ueta
Keyword(s):  
Endothelial Cells ◽  
Cerebral Endothelial Cells ◽  
Oxidant Damage

Electron Microscopic Immunolocalization of Basic Fibroblast Growth Factor-Like Molecules in Capillary Endothelial Cells

1998 ◽  
Vol 4 (S2) ◽  
pp. 1100-1101
Author(s):  
Ranan Gullhan Aktas ◽  
Robert J. Kayton
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Immunogold Labeling ◽  
Fibroblast Growth ◽  
Electron Microscopic ◽  
Adult Rats

Basic fibroblast growth factor (bFGF) is a potent angiogenic polypeptide. It promotes angiogenesis in vivo and in vitro by stimulating migration, proliferation and proteolytic activity of endothelial cells. Whereas several effects of exogenous bFGF on endothelial cells have been described, it has remained unclear how endogenous bFGF produced by vascular endothelial cells regulate angiogenesis.To further investigate functional implications of the distribution of bFGF, we undertook the present study. Our aims were (i) to identify the specific location of bFGF in endothelial cells using electron microscopy immunogold labeling technique (ii) to determine the distribution of bFGF in capillaries of different types of tissues.Tissue samples from sciatic nerve, hippocampus, adrenal gland and kidney of normal adult rats were fixed in 4% paraformaldehyde/1 to 5% glutaraldehyde and embedded in Spurr's resin. Ultrathin sections were labeled with either polyclonal (F3393-Sigma) or monoclonal antibodies (F6162-Sigma, C3316-ZymoGenetics) specific for bFGF using a two-step immunogold labeling method.

ECGF and heparin determine differentiation of cloned cerebral endothelial cells in vitro

1993 ◽  
Vol 20 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Albert Amberger ◽  
Peter F. Lemkin ◽  
Peter Sonderegger ◽  
Hans C. Bauer
Keyword(s):  
Endothelial Cells ◽  
Cerebral Endothelial Cells
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