Myelin-Independent Therapeutic Potential of Canine Glial-Restricted Progenitors Transplanted in Mouse Model of Dysmyelinating Disease

Background: Dysfunction of glia contributes to the deterioration of the central nervous system in a wide array of neurological disorders, thus global replacement of glia is very attractive. Human glial-restricted precursors (hGRPs) transplanted intraventricularly into neonatal mice extensively migrated and rescued the lifespan in half of the studied mice, whereas mouse GRPs (mGRPs) presented no therapeutic benefit. We studied in the same experimental setting canine GRPs (cGRP) to determine whether their therapeutic potential falls between hGRPs and mGRPs. Additional motivation for the selection of cGRPs was a potential for use in veterinary medicine. Methods: cGRPs were extracted from the brain of dog fetuses. The cells were transplanted into the anterior or posterior aspect of the lateral ventricle (LV) of neonatal, immunodeficient, dysmyelinated mice (Mbpshi, Rag2 KO; shiv/rag2). Outcome measures included early cell biodistribution, animal survival and myelination assessed with MRI, immunohistochemistry and electron microscopy. Results: Grafting of cGRP into posterior LV significantly extended animal survival, whereas no benefit was observed after anterior LV transplantation. In contrast, myelination of the corpus callosum was more prominent in anteriorly transplanted animals. Conclusions: The extended survival of animals after transplantation of cGRPs could be explained by the vicinity of the transplant near the brain stem.

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Therapeutic Potential of Canine Glial Restricted Progenitors Transplanted in Mouse Model of Demyelinating Disease

10.21203/rs.3.rs-89982/v1 ◽

2020 ◽

Author(s):

Luiza Stanaszek ◽

Malgorzata Majchrzak ◽

Katarzyna Drela ◽

Piotr Rogujski ◽

Joanna Sanford ◽

...

Keyword(s):

Demyelinating Disease ◽

Therapeutic Potential ◽

Companion Animals ◽

Therapeutic Benefit ◽

Posterior Aspect ◽

Cell Behaviour ◽

Animal Survival ◽

The Central Nervous System ◽

The Brain ◽

Selection Of

Abstract Background: Dysfunction of glia contributes to the deterioration of the central nervous system in a wide array of neurological disorders, thus global replacement strategies of glia are very attractive. Human glial restricted precursors (hGRPs) transplanted intraventricularly into neonatal mice extensively migrated and rescued lifespan in half of studied mice, while mouse GRPs (mGRPs) presented no therapeutic benefit. We hypothesized that the intrinsic developmental program (IDP) might be one of the main drivers of cell behaviour after grafting, with long migration distance and late myelination for hGRPs, compared to limited migration and early myelination for mGRPs. We studied in the same experimental setting canine GRPs (cGRP) to determine whether their migration, myelination and subsequent therapeutic potential falls between hGRPs and mGRPs. Additional motivation for selection of cGRPs was a potential for use in veterinary medicine due to growing population of dogs as companion animals. Methods: cGRPs were extracted from the brain of dog foetuses. The cells transplanted (4x105 cells) into anterior or posterior aspect of the lateral ventricle (LV) of neonatal, immunodeficient, dysmyelinated mice (shiverer, MBPshi/shi, rag2-/-). Outcome measures included early cell biodistribution, animal survival and myelination assessed with MRI, immunohistochemistry and electron microscopy. Results: Grafting of cGRP into posterior LV significantly extended animal survival, while no benefit was observed after anterior LV transplantation. In contrast, myelination of the corpus callosum was more prominent in anteriorly transplanted animals. Conclusions: The extended survival of animals after transplantation of cGRPs could be explained by the vicinity of transplant near the brain stem.

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RAS in the Central Nervous System: Potential Role in Neuropsychiatric Disorders

Current Medicinal Chemistry ◽

10.2174/0929867325666180226102358 ◽

2018 ◽

Vol 25 (28) ◽

pp. 3333-3352 ◽

Cited By ~ 21

Author(s):

Natalia Pessoa Rocha ◽

Ana Cristina Simoes e Silva ◽

Thiago Ruiz Rodrigues Prestes ◽

Victor Feracin ◽

Caroline Amaral Machado ◽

...

Keyword(s):

Blood Pressure ◽

Central Nervous System ◽

Nervous System ◽

Therapeutic Potential ◽

Neuropsychiatric Disorders ◽

Extensive Literature ◽

Ang Ii ◽

Mas Receptor ◽

The Central Nervous System ◽

The Brain

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.

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Genetic Approaches Using Zebrafish to Study the Microbiota–Gut–Brain Axis in Neurological Disorders

Cells ◽

10.3390/cells10030566 ◽

2021 ◽

Vol 10 (3) ◽

pp. 566

Author(s):

Jae-Geun Lee ◽

Hyun-Ju Cho ◽

Yun-Mi Jeong ◽

Jeong-Soo Lee

Keyword(s):

Neurological Disorders ◽

Genetic Model ◽

Molecular Genetic ◽

Autism Spectrum ◽

Behavioral Abnormalities ◽

Bidirectional Signaling ◽

Intestinal Dysbiosis ◽

The Central Nervous System ◽

The Brain

The microbiota–gut–brain axis (MGBA) is a bidirectional signaling pathway mediating the interaction of the microbiota, the intestine, and the central nervous system. While the MGBA plays a pivotal role in normal development and physiology of the nervous and gastrointestinal system of the host, its dysfunction has been strongly implicated in neurological disorders, where intestinal dysbiosis and derived metabolites cause barrier permeability defects and elicit local inflammation of the gastrointestinal tract, concomitant with increased pro-inflammatory cytokines, mobilization and infiltration of immune cells into the brain, and the dysregulated activation of the vagus nerve, culminating in neuroinflammation and neuronal dysfunction of the brain and behavioral abnormalities. In this topical review, we summarize recent findings in human and animal models regarding the roles of the MGBA in physiological and neuropathological conditions, and discuss the molecular, genetic, and neurobehavioral characteristics of zebrafish as an animal model to study the MGBA. The exploitation of zebrafish as an amenable genetic model combined with in vivo imaging capabilities and gnotobiotic approaches at the whole organism level may reveal novel mechanistic insights into microbiota–gut–brain interactions, especially in the context of neurological disorders such as autism spectrum disorder and Alzheimer’s disease.

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Intake of Anti-Epileptic Drugs and their Influences on Sexual Dysfunctions

Pakistan BioMedical Journal ◽

10.52229/pbmj.v3i2.15 ◽

2021 ◽

Vol 3 (2) ◽

Author(s):

Roheela Yasmeen ◽

Nida Mobeen ◽

Muhammad Amjad Khan ◽

Irfan Aslam ◽

Samia Chaudhry

Keyword(s):

Quality Of Life ◽

Sexual Dysfunction ◽

Neurological Disorders ◽

Penile Erection ◽

The Central Nervous System ◽

Relationship Of ◽

The Relationship ◽

The Brain ◽

Psychiatric Problems

Epilepsy which is also called seizures disorder is an uncontrolled action of the central nervous system. Itis not a single disease but a set of neurological disorders. Actually in this situation, the brain does notreceive a precise signal and as a result an abnormal condition is produced that is usually involuntary inaction. In this review, we aimed to focus on the relationship of anti-epileptic drugs with sexual dysfunctionand adaptation of better remedies that improve a patient’s family life. Sexual dysfunction is a commoncomorbidity in people with epilepsy which badly affects their quality of life. Sexual dysfunction is causedby different factors like psychiatric problems, anti-epileptic drugs (AEDs) and social factors etc. Sexualdysfunctions include ejaculatory failure, lessen libido, penile erection in men and irregular menstrual cyclein women. Common drugs such as Topiramate, Gabapentin (GBP), Valproate (VA), Carbamazepine (CBZ),Olanzapine (OL) and Risperidone (RTG) that are in practice to treat epilepsy usually produced adverseeffect on sexual dysfunction. Even though a lot of studies have been carried out to control sexualdysfunction in epilepsy’s patient, but still research is going on. Medicine such as Cyproheptadine,Mianserin, Buspirone, Yohimbine were found better to treat epilepsy with minimum side effects of sexualdysfunction. Moreover, it is also seen that certain vasodilators, folate , and vitamin supplements areeffective in improving the quality of life.

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Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

Molecules ◽

10.3390/molecules25081929 ◽

2020 ◽

Vol 25 (8) ◽

pp. 1929 ◽

Cited By ~ 6

Author(s):

Salman Ul Islam ◽

Adeeb Shehzad ◽

Muhammad Bilal Ahmed ◽

Young Sup Lee

Keyword(s):

Drug Delivery ◽

Neurological Disorders ◽

Neurological Diseases ◽

Nasal Delivery ◽

Intranasal Route ◽

Drug Molecules ◽

Surface Enhanced ◽

Effective Delivery ◽

The Central Nervous System ◽

The Brain

Although the global prevalence of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs’ entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices.

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Nanoparticle-Based Technology Approaches to the Management of Neurological Disorders

International Journal of Molecular Sciences ◽

10.3390/ijms21176070 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6070 ◽

Cited By ~ 2

Author(s):

Tao Ming Sim ◽

Dinesh Tarini ◽

S. Thameem Dheen ◽

Boon Huat Bay ◽

Dinesh Kumar Srinivasan

Keyword(s):

Neurological Disorders ◽

Pathological Condition ◽

Cerebrovascular Diseases ◽

Drug Bioavailability ◽

Tissue Specific ◽

The Central Nervous System ◽

Cns Drugs ◽

Treatment And Diagnosis ◽

The Brain ◽

Target Side

Neurological disorders are the most devastating and challenging diseases associated with the central nervous system (CNS). The blood-brain barrier (BBB) maintains homeostasis of the brain and contributes towards the maintenance of a very delicate microenvironment, impairing the transport of many therapeutics into the CNS and making the management of common neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), cerebrovascular diseases (CVDs) and traumatic brain injury (TBI), exceptionally complicated. Nanoparticle (NP) technology offers a platform for the design of tissue-specific drug carrying systems owing to its versatile and modifiable nature. The prospect of being able to design NPs capable of successfully crossing the BBB, and maintaining a high drug bioavailability in neural parenchyma, has spurred much interest in the field of nanomedicine. NPs, which also come in an array of forms including polymeric NPs, solid lipid nanoparticles (SLNs), quantum dots and liposomes, have the flexibility of being conjugated with various macromolecules, such as surfactants to confer the physical or chemical property desired. These nanodelivery strategies represent potential novel and minimally invasive approaches to the treatment and diagnosis of these neurological disorders. Most of the strategies revolve around the ability of the NPs to cross the BBB via various influx mechanisms, such as adsorptive-mediated transcytosis (AMT) and receptor-mediated transcytosis (RMT), targeting specific biomarkers or lesions unique to that pathological condition, thereby ensuring high tissue-specific targeting and minimizing off-target side effects. In this article, insights into common neurological disorders and challenges of delivering CNS drugs due to the presence of BBB is provided, before an in-depth review of nanoparticle-based theranostic strategies.

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Tissue-Specificity of Antibodies Raised Against TrkB and p75NTR Receptors; Implications for Platelets as Models of Neurodegenerative Diseases

Frontiers in Immunology ◽

10.3389/fimmu.2021.606861 ◽

2021 ◽

Vol 12 ◽

Author(s):

Samuel Fleury ◽

Imane Boukhatem ◽

Jessica Le Blanc ◽

Mélanie Welman ◽

Marie Lordkipanidzé

Keyword(s):

Central Nervous System ◽

Neurological Disorders ◽

Blood Circulation ◽

Tissue Specificity ◽

Receptor Kinase ◽

Calcium Dependent ◽

Neuronal Growth Factor ◽

The Central Nervous System ◽

The Brain

Platelets and neurons share many similarities including comparable secretory granule types with homologous calcium-dependent secretory mechanisms as well as internalization, sequestration and secretion of many neurotransmitters. Thus, platelets present a high potential to be used as peripheral biomarkers to reflect neuronal pathologies. The brain-derived neurotrophic factor (BDNF) acts as a neuronal growth factor involved in learning and memory through the binding of two receptors, the tropomyosin receptor kinase B (TrkB) and the 75 kDa pan-neurotrophic receptor (p75NTR). In addition to its expression in the central nervous system, BDNF is found in much greater quantities in blood circulation, where it is largely stored within platelets. Levels 100- to 1,000-fold those of neurons make platelets the most important peripheral reservoir of BDNF. This led us to hypothesize that platelets would express canonical BDNF receptors, i.e., TrkB and p75NTR, and that the receptors on platelets would bear significant resemblance to the ones found in the brain. However, herein we report discrepancies regarding detection of these receptors using antibody-based assays, with antibodies displaying important tissue-specificity. The currently available antibodies raised against TrkB and p75NTR should therefore be used with caution to study platelets as models for neurological disorders. Rigorous characterization of antibodies and bioassays appears critical to understand the interplay between platelet and neuronal biology of BDNF.

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Sirtuin 2 (SIRT2): Confusing Roles in the Pathophysiology of Neurological Disorders

Frontiers in Neuroscience ◽

10.3389/fnins.2021.614107 ◽

2021 ◽

Vol 15 ◽

Author(s):

Xiuqi Chen ◽

Wenmei Lu ◽

Danhong Wu

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Rapid Growth ◽

Nicotinamide Adenine Dinucleotide ◽

Neurological Disorders ◽

Potential Role ◽

Therapeutic Strategies ◽

Nicotinamide Adenine ◽

The Central Nervous System ◽

The Brain

As a type of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, sirtuin 2 (SIRT2) is predominantly found in the cytoplasm of cells in the central nervous system (CNS), suggesting its potential role in neurological disorders. Though SIRT2 is generally acknowledged to accelerate the development of neurological pathologies, it protects the brain from deterioration in certain circumstances. This review summarized the complex roles SIRT2 plays in the pathophysiology of diverse neurological disorders, compared and analyzed the discrete roles of SIRT2 in different conditions, and provided possible explanations for its paradoxical functions. In the future, the rapid growth in SIRT2 research may clarify its impacts on neurological disorders and develop therapeutic strategies targeting this protein.

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Understanding the Exchange of Systemic HDL Particles Into the Brain and Vascular Cells Has Diagnostic and Therapeutic Implications for Neurodegenerative Diseases

Frontiers in Physiology ◽

10.3389/fphys.2021.700847 ◽

2021 ◽

Vol 12 ◽

Author(s):

Juno Van Valkenburgh ◽

Cristiana Meuret ◽

Ashley E. Martinez ◽

Vibha Kodancha ◽

Victoria Solomon ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Therapeutic Potential ◽

Large Family ◽

Systemic Circulation ◽

High Density Lipoproteins ◽

Vascular Cells ◽

Therapeutic Implications ◽

Amyloid Metabolism ◽

The Central Nervous System ◽

The Brain

High-density lipoproteins (HDLs) are complex, heterogenous lipoprotein particles, consisting of a large family of apolipoproteins, formed in subspecies of distinct shapes, sizes, and functions and are synthesized in both the brain and the periphery. HDL apolipoproteins are important determinants of Alzheimer’s disease (AD) pathology and vascular dementia, having both central and peripheral effects on brain amyloid-beta (Aβ) accumulation and vascular functions, however, the extent to which HDL particles (HLD-P) can exchange their protein and lipid components between the central nervous system (CNS) and the systemic circulation remains unclear. In this review, we delineate how HDL’s structure and composition enable exchange between the brain, cerebrospinal fluid (CSF) compartment, and vascular cells that ultimately affect brain amyloid metabolism and atherosclerosis. Accordingly, we then elucidate how modifications of HDL-P have diagnostic and therapeutic potential for brain vascular and neurodegenerative diseases.

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Using the Importance for Survival Scale to Identify Preferred Nature Scenes With Restorative Potential: A Qualitative Study

HERD Health Environments Research & Design Journal ◽

10.1177/1937586720910082 ◽

2020 ◽

Vol 13 (4) ◽

pp. 173-189

Author(s):

Carol L. Thake ◽

Matthew Bambling ◽

Sisira Edirippulige ◽

Eric Marx

Keyword(s):

Qualitative Study ◽

Emotional Response ◽

Therapeutic Potential ◽

Well Being ◽

Therapeutic Benefit ◽

Integrated System ◽

Correlational Study ◽

Verbal Responses ◽

Nature Scenes ◽

Selection Of

Background: Evidence supports the use of images of nature scenes in healthcare settings to reduce stress and improve emotional well-being. However, the literature is diverse and provides no integrated system to identify nature scenes that provide most therapeutic benefit. Objective: The current study aimed to validate and extend results of a correlational study that found the Importance for Survival Scale (IFSS) useful for selecting generally preferred nature scenes with therapeutic potential. Methods: The correlational study that tested the usefulness of the IFSS and the current qualitative study were components of a larger mixed-methods study. For the current study, general community participants ( N = 20 males, 20 females; mean age = 48 years) provided verbal responses to questions about thoughts and feelings associated with a selection of photographs of nature scenes. Data were analyzed using a content analysis approach. Results: Themes and detailed descriptors associated with preference for, and emotional response to, most- and least-liked nature scenes were produced. A proportion of those themes is directly related to the construct of Importance for Survival (IFS), whereas other themes are better explained by alternative theoretical perspectives. Conclusions: Results uphold the IFSS as an effective tool for identifying generally preferred nature scenes with restorative potential, and provide information about the relative importance of IFSS subscales that may be used to further develop and refine the IFSS, as well as guide selection of restorative nature scenes. Results also provide fine-scaled descriptive information about preference for and emotional response to nature scenes.

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