Migraine: Experimental Models and Novel Therapeutic Approaches

Migraine is a disorder affecting an increasing number of subjects. Currently, this disorder is not entirely understood, and limited therapeutic solutions are available. Migraine manifests as a debilitating headache associated with an altered sensory perception that may compromise the quality of life. Animal models have been developed using chemical, physical or genetic modifications, to evoke migraine-like hallmarks for the identification of novel molecules for the treatment of migraine. In this context, experimental models based on the use of chemicals as nitroglycerin or inflammatory soup were extensively used to mimic the acute state and the chronicity of the disorder. This manuscript is aimed to provide an overview of murine models used to investigate migraine pathophysiology. Pharmacological targets as 5-HT and calcitonin gene-related peptide (CGRP) receptors were evaluated for their relevance in the development of migraine therapeutics. Drug delivery systems using nanoparticles may be helpful for the enhancement of the brain targeting and bioavailability of anti-migraine drugs as triptans. In conclusion, the progresses in migraine management have been reached with the development of emerging agonists of 5-HT receptors and novel antagonists of CGRP receptors. The nanoformulations may represent a future perspective in which already known anti-migraine drugs showed to better exert their therapeutic effects.

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Particularities of tinnitus in children and adolescents

ORL ro ◽

10.26416/orl.33.4.2016.165 ◽

2016 ◽

Vol 4 (1) ◽

pp. 40-42

Author(s):

Alexandra Boloș ◽

Sebastian Cozma ◽

Andreea Silvana Szalontay

Keyword(s):

Quality Of Life ◽

Young Adults ◽

Children And Adolescents ◽

Psychological Factors ◽

Ambient Noise ◽

Psychological Consequences ◽

Therapeutic Approaches

Tinnitus is a common otologic symptom and probably the most troublesome. Tinnitus causes a number of physical and psychological consequences, that interfere with the quality of life of the patient. Many authors believe that the presence of tinnitus in children is a matter of lesser importance than in adults because it is met less frequently and would be a fleeting symptom, inoffensive for them (Graham, 1981). In addition, the prevalence of tinnitus during adolescence and even in young adults is increasing, possibly as a consequence of the increased ambient noise (Bulbul SF, Shargorodsky J). Various therapeutic approaches have generated different results, which led us to consider the role of psychological factors, hence the need to underline the particularities of this symptom in childhood.

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Emerging approaches for restoration of hearing and vision

Physiological Reviews ◽

10.1152/physrev.00035.2019 ◽

2020 ◽

Cited By ~ 4

Author(s):

Sonja Kleinlogel ◽

Christian Vogl ◽

Marcus Jeschke ◽

Jakob Neef ◽

Tobias Moser

Keyword(s):

Gene Therapy ◽

Hearing Aids ◽

Sensory Information ◽

Gene Replacement ◽

Therapeutic Approaches ◽

Optogenetic Stimulation ◽

Cellular Specificity ◽

Socioeconomic Burden ◽

Comprehensive Reference

Impairments of vision and hearing are highly prevalent conditions limiting the quality of life and presenting a major socioeconomic burden. For long, retinal and cochlear disorders have remained intractable for causal therapies, with sensory rehabilitation limited to glasses, hearing aids, and electrical cochlear or retinal implants. Recently, the application of gene therapy and optogenetics to eye and ear has generated hope for a fundamental improvement of vision and hearing restoration. To date, one gene therapy for the restoration of vision has been approved and undergoing clinical trials will broaden its application including gene replacement, genome editing, and regenerative approaches. Moreover, optogenetics, i.e. controlling the activity of cells by light, offers a more general alternative strategy. Over little more than a decade, optogenetic approaches have been developed and applied to better understand the function of biological systems, while protein engineers have identified and designed new opsin variants with desired physiological features. Considering potential clinical applications of optogenetics, the spotlight is on the sensory systems. Multiple efforts have been undertaken to restore lost or hampered function in eye and ear. Optogenetic stimulation promises to overcome fundamental shortcomings of electrical stimulation, namely poor spatial resolution and cellular specificity, and accordingly to deliver more detailed sensory information. This review aims at providing a comprehensive reference on current gene therapeutic and optogenetic research relevant to the restoration of hearing and vision. We will introduce gene-therapeutic approaches and discuss the biotechnological and optoelectronic aspects of optogenetic hearing and vision restoration.

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Comparison of Genetic Variants and Manifestations of OTUD6B-Related Disorder: The First Mexican Case

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/2324709620957777 ◽

2020 ◽

Vol 8 ◽

pp. 232470962095777 ◽

Cited By ~ 1

Author(s):

Maria Elena Romero-Ibarguengoitia ◽

Consuelo Cantú-Reyna ◽

Dalia Gutierrez-González ◽

Héctor Cruz-Camino ◽

Arnulfo González-Cantú ◽

...

Keyword(s):

Intellectual Disability ◽

Genetic Variants ◽

Therapeutic Approaches ◽

Multisystem Disorder ◽

Related Disorder ◽

Dysmorphic Features ◽

The Third ◽

The Central Nervous System ◽

Mexican Patient

The intellectual disability syndrome characterized by seizures and dysmorphic features was initially described in 2017 and was associated with genetic variants in the OTUD6B gene, identified by exome sequencing (ES) in a large cohort. This multisystem disorder primarily affects the central nervous system, the gastrointestinal, and the skeletal systems. In this article, we describe the first Mexican patient diagnosed by ES. The homozygous c.433C>T (p.Arg145*) variant of the OTUD6B gene confirmed this intellectual disability syndrome. In addition to seizures and other more frequently reported manifestations of this condition, this is the third patient with associated hypothyroidism and hypogammaglobulinemia, underscoring the value of screening for these conditions in other patients. The current challenge with this patient is to ensure medical management of his seizures and provide him with a better quality of life. The possibilities of additional therapeutic approaches may increase by understanding the physiopathology of the involved pathways.

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Functional Cereal Products in the Diet for Type 2 Diabetes Patients

International Journal of Food Science ◽

10.1155/2019/4012450 ◽

2019 ◽

Vol 2019 ◽

pp. 1-7

Author(s):

Ada Krawęcka ◽

Aldona Sobota ◽

Emilia Sykut-Domańska

Keyword(s):

Type 2 Diabetes ◽

Nutritional Value ◽

Glycaemic Index ◽

Modern World ◽

Diabetic Patients ◽

Therapeutic Effects ◽

Major Health ◽

Cereal Products

Type 2 diabetes has become one of the major health problems of the modern world. It is assumed that environmental factors have a significant impact on the development of the disease, and great importance is ascribed to the diet, which can be modified accordingly. The diet can exert prophylactic and therapeutic effects; changes in the diet in advanced disease can improve the quality of life of diabetic patients and minimise the risk of complications, which are the direct cause of diabetes-related death. Functional food, which has a potentially health-enhancing effect in addition to its nutritional value, has been increasingly recognised and required. Cereal products are crucial in diabetic nutrition. Their function can additionally be enhanced by fortification with compounds with proven hypoglycaemic effects. Pasta has a low glycaemic index and is a good carrier of fortifying substances; hence, it can be highly recommended in diets for diabetic patients.

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History of IgA Nephropathy Mouse Models

Journal of Clinical Medicine ◽

10.3390/jcm10143142 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3142

Author(s):

Batoul Wehbi ◽

Virginie Pascal ◽

Lina Zawil ◽

Michel Cogné ◽

Jean-Claude Aldigier

Keyword(s):

Iga Nephropathy ◽

Small Animal ◽

Experimental Models ◽

Murine Models ◽

Therapeutic Approaches ◽

Complement Components ◽

Simple Description ◽

Primary Glomerulonephritis ◽

History Of ◽

Small Animal Models

IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. It was first described in 1968 by Jean Berger and Nicole Hinglais as the presence of intercapillary deposits of IgA. Despite this simple description, patients with IgAN may present very broad clinical features ranging from the isolated presence of IgA in the mesangium without clinical or biological manifestations to rapidly progressive kidney failure. These features are associated with a variety of histological lesions, from the discrete thickening of the mesangial matrix to diffuse cell proliferation. Immunofluorescence on IgAN kidney specimens shows the isolated presence of IgA or its inconsistent association with IgG and complement components. This clinical heterogeneity of IgAN clearly echoes its complex and multifactorial pathophysiology in humans, inviting further analyses of its various aspects through the use of experimental models. Small-animal models of IgAN provide the most pertinent strategies for studying the multifactorial aspects of IgAN pathogenesis and progression. Although only primates have the IgA1 subclass, several murine models have been developed in which various aspects of immune responses are deregulated and which are useful in the understanding of IgAN physiopathology as well as in the assessment of IgAN therapeutic approaches. In this manuscript, we review all murine IgAN models developed since 1968 and discuss their remarkable contribution to understanding the disease.

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Tolvaptan in Pediatric Autosomal Dominant Polycystic Kidney Disease: From Here to Where?

Kidney Diseases ◽

10.1159/000517186 ◽

2021 ◽

pp. 1-7

Author(s):

Fei Liu ◽

Chunyue Feng ◽

Huijun Shen ◽

Huaidong Fu ◽

Jianhua Mao

Keyword(s):

Kidney Disease ◽

Polycystic Kidney Disease ◽

Pediatric Patients ◽

Autosomal Dominant ◽

Life Assessment ◽

Therapeutic Approaches ◽

Polycystic Kidney ◽

Autosomal Dominant Polycystic Kidney ◽

Ongoing Phase

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, accounting for approximately 5% of all ESRD cases worldwide. As a vasopressin receptor 2 antagonist, tolvaptan is the FDA-approved therapeutic agent for ADPKD, which is only made available to a limited number of adult patients; however, its efficacy in pediatric patients has not been reported widely. Summary: Tolvaptan was shown to delay ADPKD progression in the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 study, Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trial, and other clinical studies. In addition to its effects on aquaretic adverse events and alanine aminotransferase elevation, the effect of tolvaptan on ADPKD is clear, sustained, and cumulative. While ADPKD is a progressive disease, the early intervention has been shown to be important and beneficial in hypotheses as well as in trials. The use of tolvaptan in pediatric ADPKD involves the following challenges: patient assessment, quality of life assessment, cost-effectiveness, safety, and tolerability. The ongoing, phase 3b, 2-part study (ClinicalTrials.gov identifier: NCT02964273) on the evaluation of tolvaptan in pediatric ADPKD (patients aged 12–17 years) may help obtain some insights. Key Messages: This review focuses on the rationality of tolvaptan use in pediatric patients with ADPKD, the associated challenges, and the suggested therapeutic approaches.

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Hallucinogenic/psychedelic 5HT2A receptor agonists as rapid antidepressant therapeutics: Evidence and mechanisms of action

Journal of Psychopharmacology ◽

10.1177/0269881120986422 ◽

2021 ◽

pp. 026988112098642

Author(s):

Rafael Guimarães dos Santos ◽

Jaime EC Hallak ◽

Glen Baker ◽

Serdar Dursun

Keyword(s):

Health Care Systems ◽

Treatment Compliance ◽

Therapeutic Effects ◽

Beneficial Effects ◽

Antidepressant Effects ◽

Care Systems ◽

Drug Treatments ◽

Fast Acting

Major depressive disorder (MDD) is among the most prevalent mental health disorders worldwide, and it is associated with a reduced quality of life and enormous costs to health care systems. Available drug treatments show low-to-moderate response in most patients, with almost a third of patients being non-responders (treatment-resistant). Furthermore, most currently available medications need several weeks to achieve therapeutic effects, and the long-term use of these drugs is often associated with significant unwanted side effects and resultant reductions in treatment compliance. Therefore, more effective, safer, and faster-acting antidepressants with enduring effects are needed. Together with ketamine, psychedelics (or classic or serotoninergic hallucinogens) such as lysergic acid diethylamide (LSD), psilocybin, and ayahuasca are among the few compounds with recent human evidence of fast-acting antidepressant effects. Several studies in the 1950s to 1970s reported antidepressive and anxiolytic effects of these drugs, which are being confirmed by modern trials (LSD, one trial; psilocybin, five trials; ayahuasca, two trials). The effects of these drugs appear to be produced primarily by their agonism at serotonin (5-hydroxytryptamine, 5-HT) receptors, especially the 5-HT2A receptor. Considering the overall burden of MDD and the necessity of new therapeutic options, the promising (but currently limited) evidence of safety and efficacy of psychedelics has encouraged the scientific community to explore more fully their beneficial effects in MDD.

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Blocking LINGO-1 in vivo reduces degeneration and enhances regeneration of the optic nerve

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217316641704 ◽

2016 ◽

Vol 2 ◽

pp. 205521731664170 ◽

Cited By ~ 1

Author(s):

Melissa M Gresle ◽

Yaou Liu ◽

Trevor J Kilpatrick ◽

Dennis Kemper ◽

Qi-Zhu Wu ◽

...

Keyword(s):

Optic Nerve ◽

Axonal Regeneration ◽

Antibody Therapy ◽

Experimental Models ◽

Therapeutic Effects ◽

Axonal Loss ◽

Nerve Crush ◽

Acute Optic Neuritis ◽

Injury Models

Background Two ongoing phase II clinical trials (RENEW and SYNERGY) have been developed to test the efficacy of anti-LINGO-1 antibodies in acute optic neuritis and relapsing forms of multiple sclerosis, respectively. Across a range of experimental models, LINGO-1 has been found to inhibit neuron and oligodendrocyte survival, axon regeneration, and (re)myelination. The therapeutic effects of anti-LINGO-1 antibodies on optic nerve axonal loss and regeneration have not yet been investigated. Objective In this series of studies we investigate if LINGO-1 antibodies can prevent acute inflammatory axonal loss, and promote axonal regeneration after injury in rodent optic nerves. Methods The effects of anti-LINGO-1 antibody on optic nerve axonal damage were assessed using rodent myelin oligodendrocyte glycoprotein experimental autoimmune encephalomyelitis (EAE), and its effects on axonal regeneration were assessed in optic nerve crush injury models. Results In the optic nerve, anti-LINGO-1 antibody therapy was associated with improved optic nerve parallel diffusivity measures on MRI in mice with EAE and reduced axonal loss in rat EAE. Both anti-LINGO-1 antibody therapy and the genetic deletion of LINGO-1 reduced nerve crush-induced axonal degeneration and enhanced axonal regeneration. Conclusion These data demonstrate that LINGO-1 blockade is associated with axonal protection and regeneration in the injured optic nerve.

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The effectiveness and safety of LMWH for preventing thrombosis in patients with spinal cord injury: a meta-analysis

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02412-7 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Ze Lin ◽

Yun Sun ◽

Hang Xue ◽

Lang Chen ◽

Chenchen Yan ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Venous Thrombosis ◽

Meta Analysis ◽

Therapeutic Effects ◽

Significant Difference ◽

Cord Injury ◽

Review Manager ◽

Evident Difference

Abstract Background Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are commonly used for preventing venous thrombosis of the lower extremity in patients with traumatic spinal cord injury. Although, LMWH is the most commonly used drug, it has yet to be established whether it is more effective and safer than UFH. Further, a comparison of the effectiveness of LMWH in preventing thrombosis at different locations and different degrees of spinal cord injury has also not been clearly defined. Materials and methods Cohort studies comparing the use of LMWH and UFH in the prevention of lower limb venous thrombosis in patients with spinal cord injury were identified using PubMed. The risk of bias and clinical relevance of the included studies were assessed using forest plots. The Newcastle-Ottawa quality assessment scale was used to evaluate the quality of the included studies. The main results of the study were analyzed using Review Manager 5.3. Results A total of five studies were included in this meta-analysis. Four studies compared the effectiveness and safety of LMWH and UFH in preventing thrombosis in patients with spinal cord injury. No significant differences were found between the therapeutic effects of the two drugs, and the summary RR was 1.33 (95% CI 0.42–4.16; P = 0.63). There was also no significant difference in the risk of bleeding between the two medications, and the aggregate RR was 0.78 (95% CI 0.55–1.12; P = 0.18). When comparing the efficacy of LMWH in preventing thrombosis in different segments and different degrees of spinal cord injury, no significant differences were found. Conclusions The results of this analysis show that compared with UFH, LMWH has no obvious advantages in efficacy nor risk prevention, and there is no evident difference in the prevention of thrombosis for patients with injuries at different spinal cord segments.

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Experimental models for controlled burn injuries in rats: a systematic analysis of original methods and burn devices

Journal of Burn Care & Research ◽

10.1093/jbcr/irab234 ◽

2021 ◽

Author(s):

Stefan Morarasu ◽

Bianca-Codrina Morarasu ◽

Nicolae Ghețu ◽

Mihail-Gabriel Dimofte ◽

Radu Iliescu ◽

...

Keyword(s):

Final Analysis ◽

Experimental Models ◽

Burn Injuries ◽

Systematic Analysis ◽

Experimental Burn ◽

Controlled Burn ◽

Histological Confirmation ◽

The Right ◽

Burn Depth

Abstract AIM Despite a wide variety of models found in literature, choosing the right one can be difficult as many of them are lacking precise methodology. This study aims to analyze and compare original burn models in terms of burn device and technique, parameters, and wound depth assessment. METHODS A systematic search was performed according to PRISMA guidelines on studies describing original experimental burn models in rats. The adapted PICO formula and ARRIVE checklist were followed for inclusion and assessment of quality of studies. Characteristics of animals, burn technique, burn parameters and method of histological confirmation of burn depth were recorded. RESULTS Twenty-seven studies were included in the final analysis. Most studies used direct contact with skin for burn infliction (n=20). The rat’s dorsum was the most common site (n=18). Ten studies used manually controlled burn devices, while ten designed automatic burn devices with control over temperature (n=10), exposure time (n=5), and pressure (n=5). Most studies (n=7) used a single biopsy taken from the center of the wound to confirm burn depth immediately after burn infliction. CONCLUSION From the wide variety of burn models in current literature, our study provides an overview of the most relevant experimental burn models in rats aiding researchers to understand what needs to be addressed when designing their burn protocol. Models cannot be compared as burn parameters variate significantly. Assessment of burn depth should be done in a standardized, sequential fashion in future burn studies to increase reproducibility.

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