scholarly journals How to Improve the Antioxidant Defense in Asphyxiated Newborns—Lessons from Animal Models

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 898
Author(s):  
Hanna Kletkiewicz ◽  
Maciej Klimiuk ◽  
Alina Woźniak ◽  
Celestyna Mila-Kierzenkowska ◽  
Karol Dokladny ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Animal Models ◽  
Iron Chelation ◽  
Therapeutic Effects ◽  
Therapeutic Approaches ◽  
Protective Capacity ◽  
Neonatal Asphyxia ◽  
New Therapeutic Approaches ◽  
The Brain ◽  
Insight Into

Oxygen free radicals have been implicated in brain damage after neonatal asphyxia. In the early phase of asphyxia/reoxygenation, changes in antioxidant enzyme activity play a pivotal role in switching on and off the cascade of events that can kill the neurons. Hypoxia/ischemia (H/I) forces the brain to activate endogenous mechanisms (e.g., antioxidant enzymes) to compensate for the lost or broken neural circuits. It is important to evaluate therapies to enhance the self-protective capacity of the brain. In animal models, decreased body temperature during neonatal asphyxia has been shown to increase cerebral antioxidant capacity. However, in preterm or severely asphyxiated newborns this therapy, rather than beneficial seems to be harmful. Thus, seeking new therapeutic approaches to prevent anoxia-induced complications is crucial. Pharmacotherapy with deferoxamine (DFO) is commonly recognized as a beneficial regimen for H/I insult. DFO, via iron chelation, reduces oxidative stress. It also assures an optimal antioxidant protection minimizing depletion of the antioxidant enzymes as well as low molecular antioxidants. In the present review, some aspects of recently acquired insight into the therapeutic effects of hypothermia and DFO in promoting neuronal survival after H/I are discussed.

scholarly journals Therapeutic Effects of Hydrogen in Animal Models of Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Kyota Fujita ◽  
Yusaku Nakabeppu ◽  
Mami Noda
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Animal Studies ◽  
Clinical Symptoms ◽  
Therapeutic Effects ◽  
Therapeutic Approaches ◽  
Cellular Apoptosis ◽  
6 Hydroxydopamine

Since the first description of Parkinson's disease (PD) nearly two centuries ago, a number of studies have revealed the clinical symptoms, pathology, and therapeutic approaches to overcome this intractable neurodegenerative disease. 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) are neurotoxins which produce Parkinsonian pathology. From the animal studies using these neurotoxins, it has become well established that oxidative stress is a primary cause of, and essential for, cellular apoptosis in dopaminergic neurons. Here, we describe the mechanism whereby oxidative stress evokes irreversible cell death, and propose a novel therapeutic strategy for PD using molecular hydrogen. Hydrogen has an ability to reduce oxidative damage and ameliorate the loss of nigrostriatal dopaminergic neuronal pathway in two experimental animal models. Thus, it is strongly suggested that hydrogen might provide a great advantage to prevent or minimize the onset and progression of PD.

scholarly journals Animal models of medullary thyroid cancer: state of the art and view to the future

2017 ◽  
Vol 24 (1) ◽  
pp. R1-R12 ◽  
Author(s):  
Giovanni Vitale ◽  
Germano Gaudenzi ◽  
Luisa Circelli ◽  
Marco F Manzoni ◽  
Andrea Bassi ◽  
...  
Keyword(s):  
Animal Models ◽  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
State Of The Art ◽  
Neuroendocrine Tumour ◽  
Progression Free Survival ◽  
Therapeutic Approaches ◽  
Medullary Thyroid ◽  
New Therapeutic Approaches ◽  
Treatment Responses

Medullary thyroid carcinoma is a neuroendocrine tumour originating from parafollicular C cells accounting for 5–10% of thyroid cancers. Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid carcinoma. These drugs increase progression-free survival; however, they are often poorly tolerated and most treatment responses are transient. Animal models are indispensable tools for investigating the pathogenesis, mechanisms for tumour invasion and metastasis and new therapeutic approaches for cancer. Unfortunately, only few models are available for medullary thyroid carcinoma. This review provides an overview of the state of the art of animal models in medullary thyroid carcinoma and highlights future developments in this field, with the aim of addressing salient features and clinical relevance.

Abstract 213: Hematoma-infiltrating Macrophages Transition From Inflammatory to Reparative Programs in Patients After Intracerebral Hemorrhage

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Michael H Askenase ◽  
Brittany A Goods ◽  
Arthur F Steinschneider ◽  
Khadir Raddassi ◽  
Hannah Beatty ◽  
...  
Keyword(s):  
Animal Models ◽  
Intracerebral Hemorrhage ◽  
Acid Metabolism ◽  
Transcriptional Analysis ◽  
Rna Seq ◽  
Mass Cytometry ◽  
Inflammatory Damage ◽  
Inflammatory Profile ◽  
The Brain ◽  
Insight Into

Intracerebral hemorrhage (ICH) causes rapid recruitment of circulating leukocytes to the injury; however, the roles of these cells in disease progression and repair in the brain are poorly understood. Findings from animal models have failed to translate into effective therapies for ICH, emphasizing the importance of studying the ICH immune response in the patient population. To gain insight into the inflammatory response in patient hematomas, we are utilizing mass cytometry, flow cytometry, and RNA-seq to characterize hematoma-infiltrating leukocytes isolated from ICH patients over a 5 day period, in conjunction with the ongoing MISTIE III trial for surgical evacuation of ICH. We have found that the hematoma immune infiltrate is predominantly composed of neutrophils and macrophages recruited from the circulation, rather than CNS-resident microglia. We have observed that hematoma macrophages have acquired a distinct phenotype differing from phagocyte populations in the peripheral blood, suggesting that their gene expression is controlled by local signals in the hematoma. Preliminary transcriptional analysis of hematoma macrophages 24-50 hours post-ICH has revealed an inflammatory profile characterized by increased expression of antigen presentation, TLR signaling, glycolytic metabolism, and prostaglandin production pathways (Figure 1). Intriguingly, by 100 hours post-ICH, macrophages downregulated these pathways and engaged a wound healing program characterized by TGF-beta signaling, fatty acid metabolism, and collagen deposition (Figure 1). These findings, in agreement with our previous results in animal models of ICH, suggest that recruited macrophages may contribute not only to initial inflammatory damage, but also to clearance of the hematoma and resolution of inflammation, making them potentially ideal targets for therapeutic intervention.

scholarly journals The functional relationship of the interleukins.

1980 ◽  
Vol 151 (6) ◽  
pp. 1551-1556 ◽  
Author(s):  
K A Smith ◽  
L B Lachman ◽  
J J Oppenheim ◽  
M F Favata
Keyword(s):  
T Cell ◽  
Functional Relationship ◽  
Immunosuppressive Agents ◽  
Therapeutic Approaches ◽  
Disease States ◽  
New Therapeutic Approaches ◽  
Relationship Of ◽  
Insight Into ◽  
T Cell Growth Factor ◽  
Stimulation Of

The mechanism of the lymphoproliferative effect of the macrophage product lymphocyte-activating factor [LAF(IL1] appears to be mediated by the stimulation of the release of T cell growth factor [TCGF(IL2)] by T cells. The magnitude of the resultant T cell proliferative clonal expansion is thus dependent upon the quantity of both LAF(IL1) and TCGF(IL2) induced by antigen or lectin stimulation. These observations, coupled with the ability to measure the production and actions of these hormone-like lymphokines, should allow for increased insight into the mode of action of immunoenhancing and immunosuppressive agents, as well as for new therapeutic approaches to disease states involving T lymphocytes.

scholarly journals Proatherogenic Sialidases and Desialylated Lipoproteins: 35 Years of Research and Current State from Bench to Bedside

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 600
Author(s):  
Alexandre Mezentsev ◽  
Evgeny Bezsonov ◽  
Dmitry Kashirskikh ◽  
Mirza S. Baig ◽  
Ali H. Eid ◽  
...  
Keyword(s):  
Animal Models ◽  
Clinical Research ◽  
Low Density Lipoproteins ◽  
High Density ◽  
High Density Lipoproteins ◽  
Low Density ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Current State

This review summarizes the main achievements in basic and clinical research of atherosclerosis. Focusing on desialylation as the first and the most important reaction of proatherogenic pathological cascade, we speak of how desialylation increases the atherogenic properties of low density lipoproteins and decreases the anti-atherogenic properties of high density lipoproteins. The separate sections of this paper are devoted to immunogenicity of lipoproteins, the enzymes contributing to their desialylation and animal models of atherosclerosis. In addition, we evaluate the available experimental and diagnostic protocols that can be used to develop new therapeutic approaches for atherosclerosis.

scholarly journals The i-Motif as a Molecular Target: More Than a Complementary DNA Secondary Structure

2021 ◽  
Vol 14 (2) ◽  
pp. 96
Author(s):  
Susie L. Brown ◽  
Samantha Kendrick
Keyword(s):  
Gene Expression ◽  
Secondary Structure ◽  
Biological Function ◽  
Molecular Target ◽  
Therapeutic Approaches ◽  
Promoter Regions ◽  
New Therapeutic Approaches ◽  
G Quadruplex ◽  
Dna Elements ◽  
Insight Into

Stretches of cytosine-rich DNA are capable of adopting a dynamic secondary structure, the i-motif. When within promoter regions, the i-motif has the potential to act as a molecular switch for controlling gene expression. However, i-motif structures in genomic areas of repetitive nucleotide sequences may play a role in facilitating or hindering expansion of these DNA elements. Despite research on the i-motif trailing behind the complementary G-quadruplex structure, recent discoveries including the identification of a specific i-motif antibody are pushing this field forward. This perspective reviews initial and current work characterizing the i-motif and providing insight into the biological function of this DNA structure, with a focus on how the i-motif can serve as a molecular target for developing new therapeutic approaches to modulate gene expression and extension of repetitive DNA.

scholarly journals Kisspeptins in physiology and pathology of sex development - new diagnostic and therapeutic approaches

2014 ◽  
Vol 12 (4) ◽  
pp. 3-12
Author(s):  
Irina Leorovna Nikitina ◽  
Alekber Azizovich Bayramov ◽  
Yuliya Nikolaevna Khoduleva ◽  
Petr Dmitriyevich Shabanov
Keyword(s):  
Reproductive System ◽  
Sexual Differentiation ◽  
System Development ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Sex Development ◽  
Human Reproductive ◽  
Modern Knowledge ◽  
The Brain

The article is dedicated to mechanisms of the human reproductive system development mechanisms. The evolution of the opinions on that processes was analysed. The review of modern knowledge of molecular and genetic causes of sex development, new mechanisms of gonadal axis regulation and role of kisspeptins in pubertat start and sexual differentiation of the brain are presented. The new actual directions of scientific research as well as the applications of kisspeptin drugs for new therapeutic approaches, treatment of hormone-dependent diseases and abnormalities of sex developmentare are observed.

scholarly journals Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 350 ◽  
Author(s):  
Alessandro Zambusi ◽  
Özge Pelin Burhan ◽  
Rossella Di Giaimo ◽  
Bettina Schmid ◽  
Jovica Ninkovic
Keyword(s):  
Premature Aging ◽  
Therapeutic Approaches ◽  
Human Microglia ◽  
Transcriptional Signature ◽  
New Therapeutic Approaches ◽  
Inflammatory Phenotype ◽  
Transcriptional Changes ◽  
Aging Kinetics ◽  
The Brain

Granulins (GRN) are secreted factors that promote neuronal survival and regulate inflammation in various pathological conditions. However, their roles in physiological conditions in the brain remain poorly understood. To address this knowledge gap, we analysed the telencephalon in Grn-deficient zebrafish and identified morphological and transcriptional changes in microglial cells, indicative of a pro-inflammatory phenotype in the absence of any insult. Unexpectedly, activated mutant microglia shared part of their transcriptional signature with aged human microglia. Furthermore, transcriptome profiles of the entire telencephali isolated from young Grn-deficient animals showed remarkable similarities with the profiles of the telencephali isolated from aged wildtype animals. Additionally, 50% of differentially regulated genes during aging were regulated in the telencephalon of young Grn-deficient animals compared to their wildtype littermates. Importantly, the telencephalon transcriptome in young Grn-deficent animals changed only mildly with aging, further suggesting premature aging of Grn-deficient brain. Indeed, Grn loss led to decreased neurogenesis and oligodendrogenesis, and to shortening of telomeres at young ages, to an extent comparable to that observed during aging. Altogether, our data demonstrate a role of Grn in regulating aging kinetics in the zebrafish telencephalon, thus providing a valuable tool for the development of new therapeutic approaches to treat age-associated pathologies.

scholarly journals Understanding the development of amblyopia using macaque monkey models

2019 ◽  
Vol 116 (52) ◽  
pp. 26217-26223 ◽  
Author(s):  
Lynne Kiorpes
Keyword(s):  
Macaque Monkey ◽  
Therapeutic Approaches ◽  
Ongoing Research ◽  
History Of ◽  
Visual Motor ◽  
Perceptual Abilities ◽  
High Level ◽  
And Function ◽  
The Brain ◽  
Insight Into

Amblyopia is a sensory developmental disorder affecting as many as 4% of children around the world. While clinically identified as a reduction in visual acuity and disrupted binocular function, amblyopia affects many low- and high-level perceptual abilities. Research with nonhuman primate models has provided much needed insight into the natural history of amblyopia, its origins and sensitive periods, and the brain mechanisms that underly this disorder. Amblyopia results from abnormal binocular visual experience and impacts the structure and function of the visual pathways beginning at the level of the primary visual cortex (V1). However, there are multiple instances of abnormalities in areas beyond V1 that are not simply inherited from earlier stages of processing. The full constellation of deficits must be taken into consideration in order to understand the broad impact of amblyopia on visual and visual–motor function. The data generated from studies of animal models of the most common forms of amblyopia have provided indispensable insight into the disorder, which has significantly impacted clinical practice. It is expected that this translational impact will continue as ongoing research into the neural correlates of amblyopia provides guidance for novel therapeutic approaches.

Experimental Models of Epilepsy in Young Animals

1994 ◽  
Vol 9 (1_suppl) ◽  
pp. S3-S11 ◽  
Author(s):  
Hana Kubová ◽  
Solomon L. Moshé
Keyword(s):  
Animal Models ◽  
Experimental Models ◽  
Similar Response ◽  
Age Group ◽  
Therapeutic Approaches ◽  
Immature Brain ◽  
New Therapeutic Approaches ◽  
Epileptic Syndromes ◽  
Early Seizures ◽  
Models Of Epilepsy

Seizures occur more frequently early in life. Some of these early seizures may eventually become epilepsy. Others are reactive seizures due to excessive environmental stimuli that, in any other age group, might not have elicited a similar response. To understand the developmental aspects of seizures and epilepsy in humans, it is important to study these processes in animals of equivalent ages. In this paper, we describe several animal models of developmental seizures, including their electroclinical manifestations and their validity in respect to human epileptic syndromes. There are several factors that may account for the increased seizure susceptibility of the immature brain, including the delayed development of effective systems or synaptic networks that are involved in the suppression of seizures. A better insight of the basic pathophysiology of seizures as a function of age in animal models will lead to the development of new therapeutic approaches for the treatment of age-specific epileptic disorders in humans. (J Child Neurol 1994;9(Suppl):S3-S11).

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