Apolipoprotein E (apoE) is the primary apolipoprotein synthesized in the brain in response to injury with known neuroprotective effects exerted through antioxidant, antiinflammatory, antiexcitotoxic, and neurotrophic mechanisms. We have previously demonstrated that COG1410, an apoE mimetic peptide, exerts neuroprotective and antiinflammatory effects in a murine model of traumatic brain injury (TBI). As in TBI, ischemia-reperfusion injury is a component of acute stroke, which displays a pharmacogenetic association with the APOE4 gene. Using an intraluminal middle cerebral occlusion (MCAO) model in rats, we found that a single intravenous injection of COG1410 at 120 min post-MCAO significantly improved vestibulomotor function, decreased poststroke locomotor asymmetry, and decreased infarct volume of the ipsilateral hemisphere. These results support further exploration of a novel apoE-mimetic peptide, COG1410, as a therapeutic treatment for stroke.
Nonlinear dynamic methods are considered to be a potential tool for studying the complex behavior of the cardiovascular system. In the present study, interindividual and gender-related differences in cardiovascular (CV) responses to various stress stimuli were studied using conventional CV variables such as heart rate (HR) and blood pressure (BP), as well as a recently introduced criterion of system complexity, normalized entropy (E/H, where E is entropy and H is system energy). A group of healthy students (n = 270) of both genders (17-20 years of age) were subjected to noise exposure, mental arithmetic, arithmetic against noise and examination stress. Results showed that CV reactivity depended upon the kind of stress imposed and the gender of the subject. HR and BP stress-induced responses did not differ between men and women. However, men had higher absolute BP levels at baseline and during exposure to stressors. Stress-induced pressor responses lasted longer in men than in women. Changes in the complexity degree of CV signals, as assessed by E/H, were more pronounced and prolonged than those of HR and BP. Unlike the latter, E/H changed significantly in all stress situations for each subject tested and could be divided into two types of stress-induced response. These results allow one to conclude that E/H can better quantitate individual differences in CV stress reactivity in comparison with HR and BP. These findings suggest that stress-induced changes in CV functioning are more varied than can be revealed by applying conventional CV measures.
CO2 inhalation is currently the most common method of euthanasia for laboratory rats and mice, and it is often used for further terminal blood sampling for clinical biochemical assays. Lately, this method has been criticized due to animal welfare issues associated with some processes that develop after CO2 inhalation. The stress reaction and the value of the clinical laboratory parameters significantly depend on the used anesthetics, method, and the site of blood sampling. Especially in small rodents, an acute terminal state followed by a cascade of metabolic reactions that can affect the studied biochemical profile may develop and cause unnecessary suffering of animals. The aim of this study was to compare the stability of biochemical parameters of outbred Sprague Dawley rats and CD-1 mice serum collected after CO2 inhalation or the intramuscular injection of tiletamine–zolazepam–xylazine (TZX). The serum content of total protein and albumin, cholesterol, triglycerides, aspartate aminotransferase (AST), alanine aminotr ansferase (ALT), alkaline phosphatase (ALP), total bilirubin, and creatinine was decreased by the injection of TZX in comparison with CO2 inhalation. In addition, the levels of calcium, phosphates, chlorides and potassium were lowered by TZX vs. CO2 administration, while the level of sodium increased. Finally, the level of the majority of serum clinical biochemical parameters in rats and mice tend to be overestimated after CO2 inhalation, which may lead to masking the possible effect of anti-inflammatory drugs in animal tests. Injection anesthesia for small rodents with TZX is a more feasible method for terminal blood sampling, which also reduces the suffering of animals.
Introduction: The article presents the results of the functional tests to improve the assessment of MIA-induced osteoarthritis development and the effectiveness of NSAID therapy. Materials and methods: In the study, 26 male SD rats were used. MIA-induced osteoarthritis was simulated in the right knee joint. After an intra-articular injection of MIA, the animals were treated with ibuprofen and meloxicam. Pain assessment was studied in the following functional tests: incapacitance (hind limb weight bearing) test, von Frey test (mechanical allodynia), grip strength test, and knee diameter measurement. At the end of the study, a histological analysis of the knee joint was performed. Results and discussion: An intra-articular MIA injection reduced 1.5 times the paw withdrawal threshold. In the rats that suffered MIA-induced osteoarthritis, the difference between the diameters of the intact and injected joints was 1.05 mm, compared to 0.03 mm difference in the control group. Hind limb weight bearing asymmetry was 89.5% when simulating MIA-induced osteoarthritis. The muscular hind limb grip strength in rats with MIA-induced osteoarthritis was significantly reduced on 3rd and 7th days after simulating osteoarthritis. Ibuprofen and meloxicam showed significant efficacy in all the above tests, although ibuprofen effectiveness was more pronounced than that of meloxicam. Conclusion: The following functional tests were identified as the most significant and sufficient to assess the development of MIA-induced osteoarthritis and analgesic efficacy of NSAIDs: incapacitance test, allodynia test (von Frey filaments), measurement of hind limb grip strength and measurement of the diameter of the inflamed knee joint. The histological analysis made it possible to confirm the correspondence of the physiological response and pathological changes in the knee joint.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.