187 The Effects of Neonatal Thymectomy on the Histology of the Hippocampus and the Cognitive Function of Adult Rats

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.

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

Stroke ◽

10.1161/str.52.suppl_1.p725 ◽

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.

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Protective Effects of Edaravone in Adult Rats with Surgery and Lipopolysaccharide Administration-Induced Cognitive Function Impairment

PLoS ONE ◽

10.1371/journal.pone.0153708 ◽

2016 ◽

Vol 11 (4) ◽

pp. e0153708 ◽

Cited By ~ 14

Author(s):

Peiqi Wang ◽

Jiangbei Cao ◽

Na Liu ◽

Li Ma ◽

Xueyue Zhou ◽

...

Keyword(s):

Cognitive Function ◽

Protective Effects ◽

Adult Rats ◽

Function Impairment

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The mechanism of lipopolysaccharide administration-induced cognitive function impairment caused by glucose metabolism disorder in adult rats

Saudi Journal of Biological Sciences ◽

10.1016/j.sjbs.2019.06.017 ◽

2019 ◽

Vol 26 (6) ◽

pp. 1268-1277

Author(s):

Yiri Du ◽

Hongwei Cui ◽

Yunfeng Xiao ◽

Jianbo Li ◽

Engboer Su ◽

...

Keyword(s):

Cognitive Function ◽

Glucose Metabolism ◽

Adult Rats ◽

Metabolism Disorder ◽

Function Impairment ◽

Glucose Metabolism Disorder

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Effects of a Single Dose of Erythropoietin on Motor Function and Cognition after Focal Brain Ischemia in Adult Rats

Prague Medical Report ◽

10.14712/23362936.2014.1 ◽

2014 ◽

Vol 115 (1-2) ◽

pp. 5-15 ◽

Cited By ~ 5

Author(s):

Michaela Hralová ◽

Eva Plaňanská ◽

Yvona Angerová ◽

Andrea Jadwiszczoková ◽

Jana Bortelová ◽

...

Keyword(s):

Body Weight ◽

Cognitive Function ◽

Motor Function ◽

Brain Ischemia ◽

Morris Water Maze Test ◽

Control Group ◽

Adult Rats ◽

The Third ◽

Swimming Test ◽

Focal Brain Ischemia

We tested the influence of erythropoietin (EPO), a basic cytokine in erythropoiesis regulation, on the process of motor function and cognition after focal brain ischemia induced by a local application of endothelin. Endothelin-1 (ET-1) induced short lasting strong vasoconstriction, with described impact on the structure and on the function of neuronal cells. Neurological description of motor function and Morris water maze test (the swimming test is one of most widely used methods for studying cognitive functions in rodents) were used to study the process of learning and memory in three-month-old male albino Wistar rats (n=52). Both tests were performed one week before, and three weeks after ischemia induction (endothelin application on the cortex in the area of a. cerebri media dx.). Experimental group received i.p. injection of EPO (5,000 IU/kg body weight, 10 min before endothelin application). Control group of animals received one i.p. injection of saline at the dose of 1 ml/kg body weight at the same time. Only sham surgery was performed in the third group of animals. Rats with EPO pretreatment before the experimental lesion exhibited significantly better motor and cognitive function then those with saline injection. No significant changes in the motor and cognitive function were found in the third group of rats (sham operated controls).

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Further Studies on the Ultrastructure of Harderian Gland in Adult Rats

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100051451 ◽

1974 ◽

Vol 32 ◽

pp. 288-289

Author(s):

Alfredo Feria-Velasco ◽

Guadalupe Tapia-Arizmendi

Keyword(s):

Fine Structure ◽

Domestic Fowl ◽

Animal Species ◽

Acinar Cells ◽

Harderian Gland ◽

Myoepithelial Cells ◽

The Other ◽

Albino Rats ◽

Adult Rats ◽

Cell Components

The fine structure of the Harderian gland has been described in some animal species (hamster, rabbit, mouse, domestic fowl and albino rats). There are only two reports in the literature dealing on the ultrastructure of rat Harderian gland in adult animals. In one of them the author describes the myoepithelial cells in methacrylate-embbeded tissue, and the other deals with the maturation of the acinar cells and the formation of the secretory droplets. The aim of the present work is to analize the relationships among the acinar cell components and to describe the two types of cells located at the perifery of the acini.

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Biodegradable polyester neuroprostheses promote the reconnection of separated peripheral nerve stubs

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100130109 ◽

1992 ◽

Vol 50 (2) ◽

pp. 1094-1095

Author(s):

Beverly L. Giammara ◽

Jennifer S. Stevenson ◽

Peggy E. Yates ◽

Robert H. Gunderson ◽

Jacob S. Hanker

Keyword(s):

Image Analysis ◽

Basement Membrane ◽

Periodic Acid ◽

Light And Electron Microscopy ◽

Computer Assisted ◽

Type Iii Collagen ◽

Image Analysis System ◽

Biodegradable Polyester ◽

Adult Rats ◽

Type Iv

An 11mm length of sciatic nerve was removed from 10 anesthetized adult rats and replaced by a biodegradable polyester Vicryl™ mesh sleeve which was then injected with the basement membrane gel, Matrigel™. It was noted that leg sensation and movement were much improved after 30 to 45 days and upon sacrifice nerve reconnection was noted in all animals. Epoxy sections of the repaired nerves were compared with those of the excised segments by the use of a variation of the PAS reaction, the PATS reaction, developed in our laboratories for light and electron microscopy. This microwave-accelerated technique employs periodic acid, thiocarbohydrazide and silver methenamine. It stains basement membrane or Type IV collagen brown and type III collagen (reticulin), axons, Schwann cells, endoneurium and perineurium black. Epoxy sections of repaired and excised nerves were also compared by toluidine blue (tb) staining. Comparison of the sections of control and repaired nerves was done by computer-assisted microscopic image analysis using an Olympus CUE-2 Image Analysis System.

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