awake-rat-model-ischemic-stroke-with-neuropsychiatric-complications

Awake Rat Model of Ischemic Stroke with Neuropsychiatric Complications During a Seven-Day Observation

The translational model of experimental stroke in rats induced by a gas embolism was created to clarify the features of stroke's development and to ...

Russian Federation

For evaluation of the effect of high-fat diet on the development of diabetic complications, the rats were maintained on standard or high-fat diet. In 3 weeks, diabetes mellitus was modeled by single intraperitoneal injection of streptozotocin. Changes in hematological parameters, physical and biochemical parameters of the urine, and in the development of thermal allodynia were different after 15-week standard and high-fat diets.

Effect of Standard and High-Fat Diets during Modeling of Streptozotocin-Induced Diabetes in Rats on the Development of Complications.

The use of a high-fat diet, along with streptozotocin administration, can provide more profound insight into the mechanism of development of complications in diabetes, as well as their treatment. High-fat diet given over 3 weeks before intraperitoneal injection of streptozotocin in a dose of 40 mg/kg promoted the appearance of hyperglycemia in Wistar rats. The biochemical analysis of blood serum revealed increased levels of urea, triglycerides, cholesterol, AST, ALT, and concentration of inorganic phosphates and K ions in the high-fat diet group in comparison with the control. Both the biochemical analysis of the blood and histological analysis showed more pronounced abnormalities in rats receiving high-fat diet in comparison with animals receiving standard ration. These changes are the early markers for the development of nephropathy, impaired liver function, and microvascular disorders typical of patients with diabetes mellitus.

Comparison of Biochemical Parameters and Pathomorphological Changes in Rats Receiving Standard and High-Fat Diets during Modeling of Streptozotocin Diabetes.

A common method of modeling urolithiasis is the use of 1 and 0.75% ethylene glycol, or a combination of ethylene glycol with other lithogens, but too rapid progression of the disease and multiple organ toxicity have been reported. We developed a urolithiasis model in Sprague-Dawley rats, in which the animals received a relatively low concentration of ethylene glycol (0.5%), but for a long-term period (6 weeks) followed by animal observation during the 6-week recovery period. In urine samples, signs of the urolithiasis development were observed starting from the sixth week: the presence of ketones, decrease in diuresis and urine pH; in the blood, urea, protein, and hematocrit were elevated. However, no leukocytes were detected in the urine; in the blood, no shifts in differential leukocyte count and no elevation in ALT, creatinine, cholesterol, and triglycerides were observed, which indicates the absence of multiple organ failure while using 1% ethylene glycol. In addition, the animals receiving 0.5% ethylene glycol were followed up to 12 weeks in contrast to animals receiving 1% ethylene glycol (the experiment in this case was stopped during the third week for ethical reasons).

Discerning Comparison of 1 and 0.5% Ethylene Glycol in Sprague-Dawley Rats with Modeled Urolithiasis.

A model of a chronic lung inflammation in SPF Sprague-Dawley rats was developed by repeated intratracheal administration of LPS in a dose of 0.4 mg/kg. On day 22 of the study, male rats treated with LPS have relative monocytopenia and reduced mean concentration of hemoglobin in the erythrocyte and the mean platelet volume in comparison with the control animals (saline). Intratracheal administration of LPS induced an inflammatory process in the lungs characterized by focal atelectasis, compensatory emphysematous expansion of subpleural pulmonary acini, focal mononuclear and neutrophilic perivascular and peribronchial infiltration, and minor focal mononuclear and neutrophilic infiltration of the alveolar walls. Against the background of LPS administration, germinal centers appeared in the lymphoid follicles of the white pulp of the spleen, and focal mononuclear infiltration of the tracheal mucosa and/or submucosa was observed in some animals.

Modeling of Chronic Lung Inflammation in Rats by Repeated Intratracheal Administration of LPS.

Type 2 diabetes mellitus develops due to a combination of genetic and environmental factors. C57BL/6 mice prone to obesity and leptin resistance were kept on a high-fat diet for 21 weeks. The animals showed a significant increase in fasting and postprandial glucose levels and body weight, the development of insulin resistance, and by week 18, an increase in the serum TNFα level. Metformin therapy at a dose of 250 mg/kg was effective against the background of disturbances in carbohydrate metabolism: animals showed a significant decrease in insulin resistance and TNFα level.

Characterization of Risk Factors for Modeling of Type 2 Diabetes Mellitus Induced by a High-Fat Diet in C57BL/6 Mice.

Creating of a scar model in laboratory animals is the most acceptable option for the preclinical search of scar treatment. However, due to high skin regeneration rate in laboratory rodents, creating an optimal animal model of scar formation is a challenge. Here we describe five methods for modeling a scar tissue in rats that we have tested. These methods allowed achieving different histopathological features and different stages of skin scar formation.

Experimental Approaches to Scar Modeling through Mechanical Skin Damage and Chemical Burn in Sprague Dawley Rats.

We present a two-stage model for the study of chronic hind limb ischemia in rats. In the area of ischemia, sclerotic changes with atrophic rhabdomyocytes and reduced vascularization were revealed. CD31 expression in the endothelium increased proportionally to the number of vessels in the ischemic zone, and at the same time, focal expression of βIII-tubulin was detected in the newly formed nerve fibers. These histological features are equivalent to the development of peripheral arterial disease in humans, which allows using our model in the search for new therapeutic strategies.

Pathological Changes in the Gastrocnemius Muscle throughout Hind Limb Ischemia Modeling in Rats.

PT1 peptide isolated from the venom of spider Geolycosa sp. is a modulator of P2X3 receptors that play a role in the development of inflammation and the transmission of pain impulses. The anti-inflammatory and analgesic efficacy of the PT1 peptide was studied in a model of complete Freund's adjuvant-induced paw inflammation in CD-1 mice. The analgesic activity of PT1 peptide was maximum after intramuscular injection at a dose of 0.01 mg/kg, which surpassed the analgesic effect of diclofenac at a dose of 1 mg/kg. The anti-inflammatory activity was maximum after intramuscular injection at a dose of 0.0001 mg/kg; a decrease in paw thickness was observed as soon as 2 h after the administration of the PT1 peptide against the background of inflammation development. All tested doses of PT1 peptide showed high anti-inflammatory activity 4 and 24 h after administration. PT1 peptide at a dose of 0.01 mg/kg when injected intramuscularly simultaneously produced high anti-inflammatory and analgesic effects compared to other doses of the peptide. Increasing the dose of PT1 peptide led to a gradual decrease in its analgesic and anti-inflammatory activity; increasing the dose of intramuscular injection to 0.1 and 1 mg/kg is inappropriate.

Study of PT1 Peptide Analgesic and Anti-Inflammatory Activity on a Local Inflammation Model in Mice CD-1.

Poloxamer 188 (P188) was tested for effect on medullary hematopoiesis in aplastic anemia. P188 was administered to CBA mice with developing anemia via oral gavage at doses of 10, 100, and 500 mg/kg. A dose-dependent effect was observed, including an increase in erythrocyte count, hemoglobin, and reticulocyte count. The parameters remained low and suggested mild anemia on day 21 in a group treated with carboplatin. P188 was assumed to exert a beneficial effect on the blood cell composition, which is distorted by cytostatic drugs.

Efficacy of Poloxamer 188 in Carboplatin-Induced Aplastic Anemia Model in CBA Mice.

We propose a new model of blood loss in awake rats with volume loss up to 40% of total blood volume in the phase of hemorrhagic shock and partial blood replacement up to final blood loss up to 30% of total blood volume. During blood withdrawal, the rats showed manifestation of baroreflex, increased blood levels of glucose and lactate, and decreased concentration of oxyhemoglobin. Partial blood volume compensation was followed by recovery of hemodynamics the levels of glucose and oxyhemoglobin. Thus, taking into account the awake status of rats and compensatory mechanisms, our model of blood loss with a fixed volume of blood drawing and its partial compensation is a relevant model for studying the efficacy of blood substitutes.

Article	Year
Effect of Standard and High-Fat Diets during Modeling of Streptozotocin-Induced Diabetes in Rats on the Development of Complications. Bulletin of experimental biology and medicine\| PubMed ID: 33893947	2021
Comparison of Biochemical Parameters and Pathomorphological Changes in Rats Receiving Standard and High-Fat Diets during Modeling of Streptozotocin Diabetes. Bulletin of experimental biology and medicine\| PubMed ID: 35001304	2022
Discerning Comparison of 1 and 0.5% Ethylene Glycol in Sprague-Dawley Rats with Modeled Urolithiasis. Bulletin of experimental biology and medicine\| PubMed ID: 36210427	2022
Modeling of Chronic Lung Inflammation in Rats by Repeated Intratracheal Administration of LPS. Bulletin of experimental biology and medicine\| PubMed ID: 36322314	2022
Characterization of Risk Factors for Modeling of Type 2 Diabetes Mellitus Induced by a High-Fat Diet in C57BL/6 Mice. Bulletin of experimental biology and medicine\| PubMed ID: 38491257	2024
Experimental Approaches to Scar Modeling through Mechanical Skin Damage and Chemical Burn in Sprague Dawley Rats. Bulletin of experimental biology and medicine\| PubMed ID: 38733481	2024
Pathological Changes in the Gastrocnemius Muscle throughout Hind Limb Ischemia Modeling in Rats. Bulletin of experimental biology and medicine\| PubMed ID: 38954303	2024
Study of PT1 Peptide Analgesic and Anti-Inflammatory Activity on a Local Inflammation Model in Mice CD-1. Bulletin of experimental biology and medicine\| PubMed ID: 39093473	2024
Efficacy of Poloxamer 188 in Carboplatin-Induced Aplastic Anemia Model in CBA Mice. Doklady biological sciences : proceedings of the Academy of Sciences of the USSR, Biological sciences sections\| PubMed ID: 39847216	2025
Experimental Model of Partially Recovered Blood Loss in Awake Rats. Bulletin of experimental biology and medicine\| PubMed ID: 40445544	2025

Natalya A. Borozdina

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