The high attrition rates in glioblastoma (GB) therapeutic development stem largely from preclinical models that fail to adequately recapitulate the dynamic tumor–host ecosystem. Unlike previous reviews that characterize glioma cell lines in isolation, this article integrates tumor biology with the distinct neuro-immune–endocrine landscapes of major laboratory rat strains. We critically evaluate standard rat malignant glioma cell lines (C6, F98, RG2, 9L) alongside transplantable tissue models (GB 101.8, GB 15/47), which offer enhanced translational relevance, demonstrating that the predictive value of any model is contingent upon the specific “glioma model and host strain” pairing and the individual physiological characteristics of the host. We provide evidence that strain-specific hypothalamic–pituitary–adrenal (HPA) axis reactivity (e.g., hyper-reactive Fischer 344 versus normo-reactive Wistar) acts as a decisive, yet often overlooked, modulator of the tumor microenvironment and therapeutic response. The review delineates the utility and limitations of these models, specifically addressing the MHC incompatibilities of the widely used C6 model in immunotherapy research, while contrasting it with the immune-evasive phenotypes of RG2 and the GB 101.8 tissue model. Furthermore, we highlight the superiority of tissue transplants in preserving cellular polyclonality and diffuse infiltration patterns compared to the circumscribed growth often observed in cell line-derived tumors. Consequently, we propose a strategic selection paradigm wherein immunogenic models serve as bioindicators of host immunocompetence, while invasive, non-immunogenic systems (F98, RG2, and GB 101.8) are utilized to investigate therapeutic resistance and systemic host-tumor interactions.
Circadian rhythm disruption induced by exposure to light—excessive in duration and intensity (dark deprivation)—and the impact of hepatotoxins are both significant risk factors for liver pathology. The purpose of this research was to evaluate the potentially synergistic effects of continuous lighting and carbon tetrachloride (CCl4) toxicity on the structural and functional organization and daily (circadian) rhythmicity of the liver in rats, as well as to look at the corrective capability of exogenous melatonin under such influences. The experiment was conducted on 200 outbred 6-month-old Wistar rat males, which were distributed into five groups, including a control (normal light/dark cycle), dark deprivation (constant light), CCl4 intoxication, and combined exposure to CCl4 and dark deprivation with or without melatonin administration (0.3 mg/kg). Histological, immunohistochemical (Ki-67, Per2, and Bmal1), biochemical, and ELISA methods were used. Circadian rhythms were analyzed using cosinor. It was shown that dark deprivation and CCl4 intoxication act synergistically, potentiating liver damage. The most severe necrosis (54.17 ± 9.13%), steatosis (57.85 ± 12.14%), and suppression of regenerative potential (decreased proportion of binucleated hepatocytes to 2.17 ± 0.21%) were observed in the group with combined exposure. This correlated with a substantial decline in melatonin content in blood plasma (7.85 ± 2.1 pg/mL) and a profound disruption in circadian rhythms. Administration of exogenous melatonin exerted pronounced hepatoprotective and chronotropic effects: it significantly reduced pathological changes (necrosis reduced to 16.35 ± 6.17%), stimulated regeneration (binucleated hepatocytes increased to 13.57 ± 0.81%), and restored the circadian rhythms of the studied parameters to levels close to those of the control. The key pathogenetic link in the potentiation of CCl4 hepatotoxicity under dark deprivation is light-induced deficiency of endogenous melatonin. Exogenous melatonin demonstrated high efficacy in correcting both structural and functional damage and liver desynchronosis, confirming its therapeutic potential under conditions of combined exposure to chronodisruptors and toxins.
The human and animal reproductive system is sensitive to temperature, but there are very few studies devoted to the effects of hypothermia on mammalian reproduction. The widespread application of therapeutic hypothermia requires a comprehensive investigation of the delayed effects of low temperature on a variety of physiological systems. Hibernating mammals have a significant potential to reactivate the reproductive system after prolonged hypothermia and can serve an important experimental model for the development of new methods of prevention and treatment of human reproductive diseases. This review analyses currently available data on hypothermia-related disorders in the male reproductive system of mammals and addresses the mechanisms of natural protection of the reproductive function in hibernating mammals.
Rationale. Polyethylene glycol is a water-soluble polymer that can be used for tissue impregnation for subsequent histological sectioning. This material has been reported to provide excellent preservation of tissue morphological features comparable to that of epoxy resins, and the sections obtained can be successfully used for immunohistochemistry. The corresponding methods for using PEG in histological routine presented in the current literature are unsystematic and generally difficult to reproduce. Aim. The purpose of this study was to assess the morphological features amenability to immunostaining of tissue sections embedded in polyethylene glycol Materials and methods. Various aspects of transferring embryo samples into PEG 1000-1500, obtaining sections, straightening them and mounting them on glass slides and staining were studied. Results. The morphological features of Mus musculus and Misgurnus fossilis (Common loach) embryos sections from PEG- and paraffin-embedded samples were compared, and pros and cons of PEG for histological processing were defined. Immunohistochemical staining of mouse embryonic brain sections was carried out using a row of antibodies using chromogenic and fluorescent detection systems. Conclusion. It has been demonstrated that PEG contributes to the preservation of the structural features of cells and intercellular material, as well as exert sparing effect on tissue protein epitopes.
Management of chronic, non-healing wounds is one of the pressing challenges in surgery. Demonstrating the effectiveness of novel drugs and medical devices is essential for their implementation in clinical practice. For this purpose, many animal models of wound healing have been developed, including in small rodents, which, however, have a specific skin structure and soft tissue regeneration. This review presents comparative characteristics of the main experimental wound models, including chronic ones, and describes their benefits and limitations. Experimental studies most commonly involve mice, rats, and rabbits due to their relatively low cost and ease of maintenance. The most widely used wound modeling method is the creation of an excisional skin defect (with or without modifications) on the back of rodents. This model is technically simple and allows for partial reproduction of various pathological conditions. Although none of the models fully replicates the chronic wound healing process, modeling in small rodents (mice, rats) and rabbits remains the primary approach for studying regeneration and evaluating the efficacy of therapeutic interventions. Excisional and incisional wound models on the back of rodents are popular due to their simplicity and reproducibility. However, a significant limitation of these models is rapid wound closure by contraction, which is uncharacteristic of human healing. Chronic wound models (splinting, tail wounds in mice or ear wounds in rabbits, hyperglycemia, and others) more accurately reproduce the healing process and better reflect clinical situations. The choice of a specific model depends on the study aims and the species-specific features of laboratory animals. Moreover, the short healing period in animals often limits the ability to assess treatment efficacy. Improving and standardizing existing wound models, as well as developing novel experimental approaches, remain important tasks for regenerative medicine and surgery.
