scholarly journals Animal Models of Metabolic Epilepsy and Epilepsy Associated Metabolic Dysfunction: A Systematic Review

2020 ◽  
Vol 13 (6) ◽  
pp. 106
Author(s):  
Uday Praful Kundap ◽  
Yam Nath Paudel ◽  
Mohd. Farooq Shaikh

Epilepsy is a serious neurological disorder affecting around 70 million people globally and is characterized by spontaneous recurrent seizures. Recent evidence indicates that dysfunction in metabolic processes can lead to the alteration of neuronal and network excitability, thereby contributing to epileptogenesis. Developing a suitable animal model that can recapitulate all the clinical phenotypes of human metabolic epilepsy (ME) is crucial yet challenging. The specific environment of many symptoms as well as the primary state of the applicable neurobiology, genetics, and lack of valid biomarkers/diagnostic tests are the key factors that hinder the process of developing a suitable animal model. The present systematic review summarizes the current state of available animal models of metabolic dysfunction associated with epileptic disorders. A systematic search was performed by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model. A range of electronic databases, including google scholar, Springer, PubMed, ScienceDirect, and Scopus, were scanned between January 2000 and April 2020. Based on the selection criteria, 23 eligible articles were chosen and are discussed in the current review. Critical analysis of the selected literature delineated several available approaches that have been modeled into metabolic epilepsy and pointed out several drawbacks associated with the currently available models. The result describes available models of metabolic dysfunction associated with epileptic disorder, such as mitochondrial respiration deficits, Lafora disease (LD) model-altered glycogen metabolism, causing epilepsy, glucose transporter 1 (GLUT1) deficiency, adiponectin responsive seizures, phospholipid dysfunction, glutaric aciduria, mitochondrial disorders, pyruvate dehydrogenase (PDH) α-subunit gene (PDHA1), pyridoxine dependent epilepsy (PDE), BCL2-associated agonist of cell death (BAD), Kcna1 knock out (KO), and long noncoding RNAs (lncRNA) cancer susceptibility candidate 2 (lncRNA CASC2). Finally, the review highlights certain focus areas that may increase the possibilities of developing more suitable animal models and underscores the importance of the rationalization of animal models and evaluation methods for studying ME. The review also suggests the pressing need of developing precise robust animal models and evaluation methods for investigating ME.

2018 ◽  
Vol 29 (7) ◽  
pp. 757-770 ◽  
Author(s):  
Nikita Nirwan ◽  
Preeti Vyas ◽  
Divya Vohora

Abstract Temporal lobe epilepsy (TLE) is the chronic and pharmacoresistant form of epilepsy observed in humans. The current literature is insufficient in explicating the comprehensive mechanisms underlying its pathogenesis and advancement. Consequently, the development of a suitable animal model mimicking the clinical characteristics is required. Further, the relevance of status epilepticus (SE) to animal models is dubious. SE occurs rarely in people; most epilepsy patients never experience it. The present review summarizes the established animal models of SE and TLE, along with a brief discussion of the animal models that have the distinctiveness and carries the possibility to be developed as effective models for TLE. The review not only covers the basic requirements, mechanisms, and methods of induction of each model but also focuses upon their major limitations and possible modifications for their future use. A detailed discussion on chemical, electrical, and hypoxic/ischemic models as well as a brief explanation on the genetic models, most of which are characterized by development of SE followed by neurodegeneration, is presented.


2012 ◽  
Vol 108 (S2) ◽  
pp. S273-S281 ◽  
Author(s):  
Amelie Deglaire ◽  
Paul J. Moughan

Animal models have been commonly used for determining amino acid digestibility in humans. This allows digestibility assays to be undertaken more efficiently than those undertaken using humans directly. The laboratory rat, usually considered as a suitable animal model, has been widely used, especially as the rat is easy to raise and relatively inexpensive to house. Although more technically demanding, the pig has also been promoted as a useful model for human nutrition studies. It may be a better model than the rat, as it is a meal eater, its upper digestive tract is anatomically and physiologically closer to that of humans and it eats most foods consumed by humans. Amino acid digestibility may be determined either at the faecal or the ileal level, the latter being considered the most accurate. This contribution evaluates the suitability of the rat and pig as animal models for assessing ileal and faecal amino acid digestibility in humans. The drawbacks and advantages of using these animal models are discussed. The review is based mainly on results from controlled studies comparing both species; however, as the number of these studies is limited, data from indirect comparisons also provide insight.


Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1233
Author(s):  
Mario García-González ◽  
Fernando Muñoz ◽  
Antonio González-Cantalapiedra ◽  
Mónica López-Peña ◽  
Nikola Saulacic

The objective of this systematic review was to synthesize all the preclinical studies carried out in periosteal distraction osteogenesis (PDO) in order to evaluate the quality using the ARRIVE guidelines. The animal models used, and the influence of the complications, were analysed in order to establish the most appropriate models for this technique. The PRISMA statements have been followed. Bibliographic sources have been consulted manually by two reviewers. Risk of bias was evaluated using the SYRCLE tool for animal studies, and the quality of the studies with the ARRIVE 2.0 guidelines. The selection criteria established by expert researchers were applied to decide which studies should be included in the review, that resulted in twenty-four studies. Only one achieved the maximum score according to the ARRIVE 2.0 guidelines. The rabbit as an animal model has presented good results in PDO, both for calvaria and jaw. Rats have shown good results for PDO in calvaria. The minipig should not be recommended as an animal model in PDO. Despite the increase in the quality of the studies since the implementation of the ARRIVE 2.0 guidelines, it would be necessary to improve the quality of the studies to facilitate the transparency, comparison, and reproducibility of future works.


2001 ◽  
Vol 49 (5) ◽  
pp. 259-267 ◽  
Author(s):  
S. Christiansen ◽  
U. R. Jahn ◽  
J. Stypmann ◽  
K. Redmann ◽  
H. H. Scheld ◽  
...  

2018 ◽  
Vol 01 (02) ◽  
pp. 95-113 ◽  
Author(s):  
Amin Tamadon ◽  
Wei Hu ◽  
Peng Cui ◽  
Tong Ma ◽  
Xiaoyu Tong ◽  
...  

Polycystic ovary syndrome (PCOS) is a gynecological metabolic and endocrine disorder with uncertain etiology. To understand the etiology of PCOS or the evaluation of various therapeutic agents, different animal models have been introduced. Considering this fact that is difficult to develop an animal model that mimics all aspects of this syndrome, but, similarity of biological, anatomical, and/or biochemical features of animal model to the human PCOS phenotypes can increase its application. This review paper evaluates the recently researched animal models and introduced the best models for different research purposes in PCOS studies. During January 2013 to January 2017, 162 studies were identified which applied various kinds of animal models of PCOS including rodent, primate, ruminant and fish. Between these models, prenatal and pre-pubertal androgen rat models and then prenatal androgen mouse model have been studied in detail than others. The comparison of main features of these models with women PCOS demonstrates higher similarity of these three models to human conditions. Thereafter, letrozole models can be recommended for the investigation of various aspects of PCOS. Interestingly, similarity of PCOS features of post-pubertal insulin and human chorionic gonadotropin rat models with women PCOS were considerable which can make it as a good choice for future investigations.


2021 ◽  
Author(s):  
Panyun Mu ◽  
Peihua Qu ◽  
Yulin Li ◽  
Jie Feng ◽  
Xu Ma ◽  
...  

Abstract Background: it is of great significance for clinical diagnosis, prevention and treatment of osteoporosis to deeply understand the pathogenesis and development process of osteoporosis through animal models of osteoporosis. This systematic review aim to summarize the modeling methods of osteoporosis, reveal the current situation and progress of animal models of osteoporosis, and compare the advantages and disadvantages of various modeling methods, so as to provide reference for clinical research.Methods: CNKI, CBM database, VIP database, Wanfang database, PubMed database and EMBASE database were searched by computer from the database establishment to December 2020 with the key words of "animal model; osteoporosis" in Chinese and English respectively. The literatures were screened according to inclusion and exclusion criteria. The methods of osteoporosis modeling, the improvement of the methods and the advantages and disadvantages of each method are summarized.Discussion: a total of 9303 related literatures were collected, and 112 eligible literatures were included. The establishment of an appropriate animal model is the key to the etiology, pathophysiology and drug therapy of osteoporosis. As the causes and pathophysiological changes of different types of OP have their own characteristics, the modeling methods are also different. Therefore, different modeling methods and experimental animals should be selected according to different experimental requirements.Systematic review registration: No


2021 ◽  
Vol 19 ◽  
Author(s):  
Flávia Gheller Schaidhauer ◽  
Higor Arruda Caetano ◽  
Guilherme Pietro da Silva ◽  
Rosane Souza da Silva

Background: The consequences of mild to severe exposure to alcohol during brain development is still a matter of debate and scientific investigation. The long-term behavioural effects of ethanol exposure have been related to impaired social skills and cognition. Zebrafish have become a suitable animal model to investigate the effects of early ethanol exposure because it is very feasible to promote drug delivery during early development. Objective: The goal of the current report is to review existing behavioural studies addressing the impact of early alcohol exposure using zebrafish to determine whether these models resemble the behavioural effects of early alcohol exposure in humans. Methods: A comprehensive search of biomedical databases was performed using the operation order: “ZEBRAFISH AND BEHAV* AND (ETHANOL OR ALCOHOL)”. The eligibility of studies was determined using the PICOS strategy, contemplating the population as zebrafish, intervention as exposure to ethanol, comparison with a non-exposed control animal, and outcomes as behavioural parameters. Results: The systematic search returned 29 scientific articles as eligible. The zebrafish is presented as a versatile animal model that is useful to study FASD short and long-term behaviour impairments, such as anxiety, impaired sociability, aggressiveness, learning problems, memory impairment, seizure susceptibility, sleep disorders, motivational problems, and addiction. Conclusion: This systematic review serves to further promote the use of zebrafish as a model system to study the pathophysiological and behavioural consequences of early alcohol exposure.


2022 ◽  
Vol 12 ◽  
Author(s):  
Wei Xia ◽  
Honglin Chen ◽  
Yiwei Feng ◽  
Nan Shi ◽  
Zongjian Huang ◽  
...  

Epstein-Barr virus (EBV) is a human herpesvirus that latently infects approximately 95% of adults and is associated with a spectrum of human diseases including Infectious Mononucleosis and a variety of malignancies. However, understanding the pathogenesis, vaccines and antiviral drugs for EBV-associated disease has been hampered by the lack of suitable animal models. Tree shrew is a novel laboratory animal with a close phylogenetic relationship to primates, which is a critical advantage for many animal models for human disease, especially viral infections. Herein, we first identified the key residues in the CR2 receptor that bind the gp350 protein and facilitate viral entry. We found that tree shrew shares 100% sequence identity with humans in these residues, which is much higher than rabbits (50%) and rats (25%). In vitro analysis showed that B lymphocytes of tree shrews are susceptible to EBV infection and replication, as well as EBV-enhanced cell proliferation. Moreover, results of in vivo experiments show that EBV infection in tree shrews resembles EBV infection in humans. The infected animals exhibited transient fever and loss of weight accompanied by neutropenia and high viremia levels during the acute phase of the viral infection. Thereafter, tree shrews acted as asymptomatic carriers of the virus in most cases that EBV-related protein could be detected in blood and tissues. However, a resurgence of EBV infection occurred at 49 dpi. Nanopore transcriptomic sequencing of peripheral blood in EBV-infected animals revealed the dynamic changes in biological processes occurring during EBV primary infection. Importantly, we find that neutrophil function was impaired in tree shrew model as well as human Infectious Mononucleosis datasets (GSE85599 and GSE45918). In addition, retrospective case reviews suggested that neutropenia may play an important role in EBV escaping host innate immune response, leading to long-term latent infection. Our findings demonstrated that tree shrew is a suitable animal model to evaluate the mechanisms of EBV infection, and for developing vaccines and therapeutic drugs against EBV.


Author(s):  
V.J.A. Montpetit ◽  
S. Dancea ◽  
S.W. French ◽  
D.F. Clapin

A continuing problem in Alzheimer research is the lack of a suitable animal model for the disease. The absence of neurofibrillary tangles of paired helical filaments is the most critical difference in the processes by which the central nervous system ages in most species other than man. However, restricting consideration to single phenomena, one may identify animal models for specific aspects of Alzheimer's disease. Abnormal fibers resembling PHF have been observed in dorsal root ganglia (DRG) neurons of rats in a study of chronic ethanol intoxication and spontaneously in aged rats. We present in this report evidence that PHF-like filaments occur in ethanol-treated rats of young age. In control animals lesions similar in some respects to our observations of cytoskeletal pathology in pyridoxine induced neurotoxicity were observed.Male Wistar BR rats (Charles River Labs) weighing 350 to 400 g, were implanted with a single gastrostomy cannula and infused with a liquid diet containing 30% of total calories as fat plus ethanol or isocaloric dextrose.


2013 ◽  
Vol 83 (3) ◽  
pp. 188-197 ◽  
Author(s):  
Rebecca L. Sweet ◽  
Jason A. Zastre

It is well established that thiamine deficiency results in an excess of metabolic intermediates such as lactate and pyruvate, which is likely due to insufficient levels of cofactor for the function of thiamine-dependent enzymes. When in excess, both pyruvate and lactate can increase the stabilization of the hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor, resulting in the trans-activation of HIF-1α regulated genes independent of low oxygen, termed pseudo-hypoxia. Therefore, the resulting dysfunction in cellular metabolism and accumulation of pyruvate and lactate during thiamine deficiency may facilitate a pseudo-hypoxic state. In order to investigate the possibility of a transcriptional relationship between hypoxia and thiamine deficiency, we measured alterations in metabolic intermediates, HIF-1α stabilization, and gene expression. We found an increase in intracellular pyruvate and extracellular lactate levels after thiamine deficiency exposure to the neuroblastoma cell line SK-N-BE. Similar to cells exposed to hypoxia, there was a corresponding increase in HIF-1α stabilization and activation of target gene expression during thiamine deficiency, including glucose transporter-1 (GLUT1), vascular endothelial growth factor (VEGF), and aldolase A. Both hypoxia and thiamine deficiency exposure resulted in an increase in the expression of the thiamine transporter SLC19A3. These results indicate thiamine deficiency induces HIF-1α-mediated gene expression similar to that observed in hypoxic stress, and may provide evidence for a central transcriptional response associated with the clinical manifestations of thiamine deficiency.


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