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.

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.

Alterations in vascular endothelial function in the aorta and mesenteric artery in type II diabetic rats

2004 ◽  
Vol 82 (3) ◽  
pp. 175-182 ◽  
Author(s):  
Takayuki Matsumoto ◽  
Kentaro Wakabayashi ◽  
Tsuneo Kobayashi ◽  
Katsuo Kamata
Keyword(s):  
Type Ii Diabetes ◽  
Mesenteric Artery ◽  
Matched Control ◽  
Contractile Response ◽  
Type Ii Diabetes Mellitus ◽  
Diabetic Rats ◽  
Vascular Endothelial ◽  
Type Ii ◽  
Adult Rats ◽  
Plasma Insulin Levels

We used the partial protection exerted by suitable dosages of nicotinamide against the β-cytotoxic effect of streptozotocin (STZ) to create an experimental diabetic syndrome in adult rats that appears closer to type II diabetes mellitus than other available animal models. The dosage of 230 mg/kg of nicotinamide given intraperitoneally 15 min before STZ administration (65 mg/kg i.v.) yielded animals with hyperglycemia (187.8 ± 17.8 vs. 103.8 ± 2.8 mg/dL in controls; P < 0.001) and preservation of plasma insulin levels. This study assessed the relationship between endothelial dysfunction and agonist-induced contractile responses in such rats. In the thoracic aorta, the acetylcholine (ACh) induced relaxation was significantly reduced and the noradrenaline (NA) induced contractile response was significantly increased in diabetic rats compared with age-matched control rats. In the superior mesenteric artery, the ACh-induced relaxation was similar in magnitude between diabetic and age-matched control rats; however, the ACh-induced endothelium-derived hyperpolarizing factor (EDHF) type relaxation was significantly weaker in diabetic rats than in the controls. The phenylephrine (PE) induced contractile response was not different between the two groups. The plasma concentration of NOx (NO2– + NO3–) was significantly lower in diabetic rats than in control rats. We conclude that vasomotor activities in conduit arteries are impaired in this type II diabetes model.Key words: aorta, contraction, endothelium-derived hyperpolarizing factor, endothelium-mediated relaxation, mesenteric artery, type II diabetes.

HUBUNGAN AKTIVITAS FISIK DENGAN FUNGSI KOGNITIF LANSIA DI PANTI WREDHA YAYASAN SOSIAL SALIB PUTIH SALATIGA

2019 ◽  
pp. 137-143
Author(s):  
Dennys Christovel Dese ◽  
Cahyo Wibowo
Keyword(s):  
Physical Activity ◽  
Cognitive Function ◽  
The Elderly ◽  
Moderate Physical Activity ◽  
Cross Sectional ◽  
Significance Level ◽  
The Social ◽  
Normal Cognitive Function ◽  
Intellectual Capacity ◽  
Independent Variable

Peningkatan jumlah lansia setiap tahunnya harus dijadikan perhatian, akibat adanya peningkatan jumlah lansia masalah yang dihadapi akan menjadi semakin kompleks, salah satunya adalah masalah yang berkaitan dengan gejala penuaan. Menurunnya kapasitas intelektual berhubungan erat dengan fungsi kognitif pada lansia. Aktivitas fisik diidentifikasi sebagai salah satu faktor yang mempengaruhi fungsi kognitif. Aktivitas fisik bermanfaat untuk lansia sebagai pencegahan dan demensia. Penelitian ini merupakan penelitian analitik observasional dengan menggunakan pendekatan cross sectional. Penelitian dilakukan di yayasan sosial Panti Wredha Salib Putih Salatiga pada bulan Juni 2018. Populasi dalam penelitian ini adalah lansia yang berumur ?60 tahun. Subjek pada penelitian ini berjumlah 16 responden. Variabel independen dalam penelitian ini adalah aktivitas fisik yang dinilai dengan menggunakan instrument GPAQ. Sedangkan variabel dependen dalam penelitian ini adalah fungsi kognitif yang dinilai dengan instrument MMSE. Terdapat 4 orang (25%) yang masuk dalam kategori fungsi kognitif normal dengan kategori aktifitas fisik sedang 1 orang dan aktifitas berat 3 orang, kemudian yang termasuk dalam kategori gangguan fungsi kognitif ringan sebanyak 11 orang (68,75%), dengan kategori aktifitas fisik sedang 8 orang dan aktifitas ringan 3 orang. Sedangkan yang termasuk dalam kategori gangguan fungsi kognitif berat, terdapat 1 orang (6,25%) dengan kategori aktifitasnya ringan. Taraf signifikansi antar variabel tingkat aktifitas fisik dan fungsi kognitif pada lansia adalah p=0.007 atau p<0,05, sehingga dapat disimpulkan ada  hubungan antara tingkat aktifitas fisik dengan fungsi kognitif pada lansia.   Increasing the number of elderly people every year should be a concern, due to an increase in the number of elderly problems faced will become increasingly complex, one of which is a problem related to the symptoms of aging. Decreased intellectual capacity is closely related to cognitive function in the elderly. Physical activity is identified as one of the factors that influence cognitive function. Physical activity is beneficial for the elderly as prevention and dementia. This study was an observational analytic study using a cross sectional approach. The study was conducted at the social foundation nursing home in the white cross in June 2018. The population in this study was elderly aged ≥60 years. The subjects in this study were 16 respondents. The independent variable in this study is physical activity that is assessed using the GPAQ instrument. While the dependent variable in this study was cognitive function which was assessed by the MMSE instrument. There are 4 people (25%) who fall into the category of normal cognitive function with moderate physical activity categories 1 person and heavy activities 3 people, then those included in the category of mild cognitive function disorders are 11 people (68.75%), with the category of physical activity being 8 people and 3 light activities. While those included in the category of severe cognitive function disorders, there is 1 person (6.25%) with a mild activity category. The significance level between the level of physical activity and cognitive function in the elderly is p = 0.007 or p <0.05, so it can be concluded that there is a relationship between the level of physical activity and cognitive function in the elderly.

Effects of Acute and Chronic Biomechanical Strain on Human Cerebral Endothelial Cells in Altering their Proteome Profile

2017 ◽  
Vol 14 (3) ◽  
Author(s):  
Nurul Farhana Jufri ◽  
Abidali Mohamedali ◽  
Seong Beom Ahn ◽  
Alberto Avolio ◽  
Mark Scott Baker
Keyword(s):  
Endothelial Cells ◽  
Cerebral Endothelial Cells ◽  
Proteome Profile ◽  
Biomechanical Strain

scholarly journals Vascular Endothelial Repair and the Influence of Circulating Antiplatelet Drugs in a Carotid Coil Model

2021 ◽  
Vol 13 ◽  
pp. 117957352110117
Author(s):  
Norihito Fukawa ◽  
Takahiro Ueda ◽  
Tomofumi Ogoshi ◽  
Yasuhide Kitazawa ◽  
Jun Takahashi
Keyword(s):  
Endothelial Cells ◽  
Carotid Artery ◽  
Vascular Endothelial Cells ◽  
Repair Process ◽  
Diabetic Rats ◽  
Antiplatelet Drugs ◽  
Endovascular Coiling ◽  
Vascular Endothelial ◽  
Embolization Coil ◽  
Endothelial Repair

Background: Clinicians may choose to administer antiplatelet medications to patients with cerebral aneurysms following endovascular coiling to prevent thrombus formation and vascular occlusion, if they fear a thrombus will form on the platinum wire where it diverges into the vessel from the aneurysm sac. However, the mechanism by which vascular endothelial cells repair a vessel in the living body in the event of a coil deviation and the effects of antiplatelet drugs on these cells have not been fully elucidated. We aimed to investigate the association between endothelial progenitor cells (EPCs) and endothelium formation at the surface of the platinum coils deployed in the carotid artery of rats, and to determine the effects of different antiplatelet drugs on this process. Subjects and Methods: We established an experimental model using normal and diabetic rats at 12 months of age. The diabetic rats were assigned to 4 different diet groups, distinguished by whether they were fed plain rat feed, or the same feed supplemented by 1 of 3 antiplatelet drugs (cilostazol, aspirin, or clopidogrel: all 0.1%) for 2 weeks, and the carotid artery was perforated by an embolization coil (“carotid coil model”). We monitored the process by which vascular endothelial cells formed the new endothelium on the surface of the coil by sampling and evaluating the region at 1, 2, and 4 weeks after placement. This repair process was also compared among 3 groups treated with different antiplatelet drugs (i.e. aspirin, clopidogrel, and cilostazol). One-way analysis of variance tests were performed to evaluate the differences in vascular thickness between groups, and P < .05 was considered statistically significant. Results: The diabetic rats showed delayed neoendothelialization and marked intimal hyperplasia. Cilostazol and clopidogrel effectively counteracted this delayed endothelial repair process. Flk1 immunostaining revealed greater expression in the diabetic rats administered cilostazol, second only to normal rats, suggesting that this agent acted to recruit EPCs. Conclusion: Neoendothelialization is delayed when vascular endothelial cells fail to function normally, which consequently leads to the formation of hyperplastic tissue. Cilostazol may remedy this dysfunction by recruiting EPCs to the site of injury.

Effect of atorvastatin on the angiogenic responsiveness of coronary endothelial cells in normal and streptozotocin (STZ) induced diabetic rats

2014 ◽  
Vol 92 (4) ◽  
pp. 338-349 ◽  
Author(s):  
Kiranj K. Chaudagar ◽  
Anita A. Mehta
Keyword(s):  
Endothelial Cells ◽  
Low Dose ◽  
Ischemia Reperfusion ◽  
Late Phase ◽  
Diabetic Rats ◽  
Lipid Lowering ◽  
Diabetic Rat ◽  
High Dose ◽  
Atorvastatin Treatment ◽  
Coronary Endothelial Cells

Atorvastatin, a lipid lowering agent, possesses various pleiotropic vasculoprotective effects, but its role in coronary angiogenesis is still controversial. Our objective was to study the effects of atorvastatin on the angiogenic responsiveness of coronary endothelial cells (cEC) from normal and diabetic rats. Male Wistar rats were distributed among 9 groups; (i) normal rats, (ii) 30 day diabetic rats, (iii) 60 day diabetic rats, (iv) normal rats administered a low dose of atorvastatin (1 mg/kg body mass, per oral (p.o.), for 15 days); (v) 30 day diabetic rats administered a low dose of atorvastatin; (vi) 60 day diabetic rats administered a low dose of atorvastatin; (vii) normal rats administered a high dose of atorvastatin (5 mg/kg, p.o., for 15 days); (viii) 30 day diabetic rats administered a high dose of atorvastatin; (ix) 60 day diabetic rats administered a high dose of atorvastatin. Each group was further divided into 2 subgroups, (i) sham ischemia–reperfusion and (ii) rats hearts that underwent ischemia–reperfusion. Angiogenic responsiveness the and nitric oxide (NO) releasing properties of the subgroups of cECs were studied using a chorioallantoic membrane assay and the Griess method, respectively. Atorvastatin treatment significantly increased VEGF-induced angiogenic responsiveness and the NO-releasing properties of cECs from all of the subgroups, compared with their respective non-treated subgroups except for the late-phase diabetic rat hearts that underwent ischemia–reperfusion, and the high dose of atorvastatin treatment groups. These effects of atorvastatin were significantly inhibited by pretreatment of cECs with l-NAME, wortmannin, and chelerythrine. Thus, treatment with a low dose of atorvastatin improves the angiogenic responsiveness of the cECs from normal and diabetic rats, in the presence of VEGF, via activation of eNOS–NO release.

scholarly journals GABAB receptor antagonist promotes hippocampal neurogenesis and facilitates cognitive function recovery following acute cerebral ischemia in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dan Song ◽  
Yaohua Chen ◽  
Cheng Chen ◽  
Lili Chen ◽  
Oumei Cheng
Keyword(s):  
Cognitive Function ◽  
Cerebral Ischemia ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Hippocampal Neurogenesis ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
In Vitro Experiments ◽  
Adult Mice

Abstract Purpose and background Previous studies have suggested that promoting endogenous neurogenesis has great significance for the recovery of cognitive dysfunction caused by cerebral ischemia (CI). Pharmacological inhibition of GABAB receptor can enhance neurogenesis in adult healthy and depressed mice. In the study, we intended to investigate the effects of GABAB receptor antagonists on cognitive function and hippocampal neurogenesis in mice following CI. Methods Adult mice were subjected to bilateral common carotid artery occlusion (BCCAO) for 20 min to induce CI and treated with CGP52432 (antagonist of GABAB receptor, CGP, 10 mg/kg intraperitoneal injection) starting 24 h after CI. The Morris water maze test was performed to test spatial learning and memory at day 28. Immunofluorescence was applied to detect neurogenesis in the DG region at day 14 and 28. In in vitro experiments, cell proliferation was detected by CCK8 and immunofluorescence, and the expression of cAMP/CREB signaling pathway-related proteins was detected by ELISA assay and Western blot. Results CGP significantly improved spatial learning and memory disorders caused by CI, and it enhanced the proliferation of neural stem cells (NSCs), the number of immature neurons, and the differentiation from newborn cells to neurons. In vitro experiments further confirmed that CGP dose-dependently enhanced the cell viability of NSCs, and immunofluorescence staining showed that CGP promoted the proliferation of NSCs. In addition, treatment with CGP increased the expression of cAMP, PKA, and pCREB in cultured NSCs. Conclusion Inhibition of GABAB receptor can effectively promote hippocampal neurogenesis and improve spatial learning and memory in adult mice following CI.

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