scholarly journals Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 192 ◽  
Author(s):  
Ana P. Spencer ◽  
Marília Torrado ◽  
Beatriz Custódio ◽  
Sara C. Silva-Reis ◽  
Sofia D. Santos ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Chemical Properties ◽  
Neurologic Diseases ◽  
Physiological Processes ◽  
Specific Accumulation ◽  
The Central Nervous System ◽  
Clinical Interest ◽  
Physical And Chemical ◽  
Neuronal Delivery

Central nervous system (CNS) disorders encompass a vast spectrum of pathological conditions and represent a growing concern worldwide. Despite the high social and clinical interest in trying to solve these pathologies, there are many challenges to bridge in order to achieve an effective therapy. One of the main obstacles to advancements in this field that has hampered many of the therapeutic strategies proposed to date is the presence of the CNS barriers that restrict the access to the brain. However, adequate brain biodistribution and neuronal cells specific accumulation in the targeted site also represent major hurdles to the attainment of a successful CNS treatment. Over the last few years, nanotechnology has taken a step forward towards the development of therapeutics in neurologic diseases and different approaches have been developed to surpass these obstacles. The versatility of the designed nanocarriers in terms of physical and chemical properties, and the possibility to functionalize them with specific moieties, have resulted in improved neurotargeted delivery profiles. With the concomitant progress in biology research, many of these strategies have been inspired by nature and have taken advantage of physiological processes to achieve brain delivery. Here, the different nanosystems and targeting moieties used to achieve a neuronal delivery reported in the open literature are comprehensively reviewed and critically discussed, with emphasis on the most recent bioinspired advances in the field. Finally, we express our view on the paramount challenges in targeted neuronal delivery that need to be overcome for these promising therapeutics to move from the bench to the bedside.

scholarly journals Permeability of the Blood-Brain Barrier and Transport of Nanobodies Across the Blood-Brain Barrier

2018 ◽  
Vol 62 (1) ◽  
pp. 59-66 ◽  
Author(s):  
I. Širochmanová ◽  
Ľ. Čomor ◽  
E. Káňová ◽  
I. Jiménez-Munguía ◽  
Z. Tkáčová ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Chemical Properties ◽  
Cost Effective ◽  
Central Nervous System Disease ◽  
Brain Barrier ◽  
Promising Alternative ◽  
Blood Brain ◽  
The Central Nervous System

Abstract The presence of a blood-brain barrier (BBB) and a blood-cerebrospinal fluid barrier presents animmense challenge for effective delivery of therapeutics to the central nervous system. Many potential drugs, which are effective at their site of action, have failed due to the lack of distribution in sufficient quantity to the central nervous system (CNS). In consequence, many diseases of the central nervous system remain undertreated. Antibodies, IgG for example, are difficult to deliver to the CNS due to their size (~155 kDa), physico-chemical properties and the presence of Fc receptor on the blood-brain barrier. Smaller antibodies, like the recently developed nanobodies, may overcome the obstacle of the BBB and enter into the CNS. The nanobodies are the smallest available antigen-binding fragments harbouring the full antigenbinding capacity of conventional antibodies. They represent a new generation of therapeutics with exceptional properties, such as: recognition of unique epitopes, target specificity, high affinity, high solubility, high stability and high expression yields in cost-effective recombinant production. Their ability to permeate across the BBBmakes thema promising alternative for central nervous system disease therapeutics. In this review, we have systematically presented different aspects of the BBB, drug delivery mechanisms employed to cross the BBB, and finally nanobodies — a potential therapeutic molecule against neuroinfections.

Synthesis, Spectral, Bio Assay, Chromatographic - Studying of New Imidazole Reagents Via Three Components Reaction

2021 ◽  
Vol 19 (7) ◽  
pp. 115-122
Author(s):  
Mohammed Nawfal Abdul Maged Alkhafaji ◽  
Hutham Abd Ali Abd Al Hussain ◽  
Dr. Nagham Mahmood Aljamali
Keyword(s):  
Nervous System ◽  
Drug Targets ◽  
Biological Activities ◽  
Drug Carrier ◽  
Chemical Properties ◽  
Cancer Drug ◽  
Condensation Process ◽  
Chromatographic Study ◽  
The Central Nervous System ◽  
Physical And Chemical

Imidazoles are part of the theophylline Reagent, found in tea leaves and coffee beans, which stimulates the central nervous system. It is found in the anti-cancer drug mercaptopurine, which fights leukemia by interfering with DNA systems. A number of prepared imidazoles, including clotrimazole, are selective inhibitors of nitric oxide synthase, which makes them interesting drug targets in inflammation, respiratory diseases and tumors of the nervous system. Other biological activities of the drug carrier imidazole relate to deregulation of the intracellular fluxes of (Ca and K) ions. Novel imidazole –heterocyclic reagents were created via cyclization process then condensation process., followed by investigation of all created new reagents via a number of spectral performances (FT.IR, H.NMR)–spectrophotometric, other physical and chemical properties, and chromatographic study with microbial studying for all new created imidazole reagents.

NEUROLOGIC DISEASES IN INFANCY AND CHILDHOOD

PEDIATRICS ◽  
1957 ◽  
Vol 19 (5) ◽  
pp. 949-957
Author(s):  
William A. Hawke ◽  
John S. Prichard
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Stem ◽  
Developmental Patterns ◽  
Basic Emotions ◽  
Neurologic Diseases ◽  
Neurologic Disorders ◽  
Infancy And Childhood ◽  
The Central Nervous System ◽  
The Brain

THE SEMINAR was conducted in four 3-hour sessions and aimed to cover the more important features of pediatric neurology. DEVELOPMENT Dr. Hawke reviewed the normal development of the central nervous system in the infant and child which is so important in the assessment of neurologic disorders in this age group. It was noted that the nervous system was particularly immature and changing rapidly in the first 2 years of life. Development was related to myelination and it was emphasized that this was not a steady process but a pattern of sequences of rapid and slow growth. Motor and sensory development appeared to develop from above and to proceed downward, so that eye-control develops before hand- and legcontrol. Development was related to three functioning levels of the central nervous system—the brain stem, the archipallium, and the neopallium. It was observed that the newborn baby functioned at the brain stem level, and to illustrate this an example was given of the hydranencephalic baby which behaves perfectly normally for the first few weeks of life. The anchipallium, which includes part of the temporal lobe, the cingulate gyrus and basal ganglia, supervenes on the brain stem and may be considered responsible for the basic emotions and some primitive motor and sensory control. The neopallium, which includes most of the cerebral hemisphere, becomes dominant in primates. Its function is intellectual rather than emotional and is responsible for skills, discrimination and fine movements. The clinical application of these developmental patterns are innumerable but illustrations were given of changes in physical signs in static brain lesions.

scholarly journals Drugs modulating the L-arginine:NO:cGMP pathway – current use in therapy

2016 ◽  
Vol 29 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Magdalena Polakowska ◽  
Jolanta Orzelska-Gorka ◽  
Sylwia Talarek
Keyword(s):  
Nitric Oxide ◽  
Central Nervous System ◽  
Nervous System ◽  
Cardiovascular Diseases ◽  
Significant Role ◽  
Current Understanding ◽  
Physiological Processes ◽  
Wide Range ◽  
The Central Nervous System ◽  
Pharmacological Profiles

AbstractNitric oxide (NO) is a relatively novel messenger that plays a significant role in a wide range of physiological processes. Currently, it is known that, both, lack and excess of NO can cause diseases, thus a lot of substances have been discovered and utilized which can change the concentration of this molecule within the organism. The aim of the present work is to provide an overview of currently used agents modulating the L-arginine:NO:cGMP pathway, as well as to summarize current understanding of their pharmacological profiles. Nowadays, most of these agents are employed particularly in the treatment of cardiovascular diseases. Further studies can hold promise for enhancing the therapeutic equipment for a variety of other impairments, such as osteoporosis, and also in treatments of the central nervous system.

scholarly journals Identification and characterization of expression profiles of neuropeptides and their GPCRs in the swimming crab, Portunus trituberculatus

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12179
Author(s):  
Shisheng Tu ◽  
Rui Xu ◽  
Mengen Wang ◽  
Xi Xie ◽  
Chenchang Bao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Expression Profile ◽  
Expression Profiles ◽  
Tissue Expression ◽  
Portunus Trituberculatus ◽  
Physiological Processes ◽  
Tissue Expression Profile ◽  
The Central Nervous System ◽  
Reproductive Processes

Neuropeptides and their G protein-coupled receptors (GPCRs) regulate multiple physiological processes. Currently, little is known about the identity of native neuropeptides and their receptors in Portunus trituberculatus. This study employed RNA-sequencing and reverse transcription-polymerase chain reaction (RT-PCR) techniques to identify neuropeptides and their receptors that might be involved in regulation of reproductive processes of P. trituberculatus. In the central nervous system transcriptome data, 47 neuropeptide transcripts were identified. In further analyses, the tissue expression profile of 32 putative neuropeptide-encoding transcripts was estimated. Results showed that the 32 transcripts were expressed in the central nervous system and 23 of them were expressed in the ovary. A total of 47 GPCR-encoding transcripts belonging to two classes were identified, including 39 encoding GPCR-A family and eight encoding GPCR-B family. In addition, we assessed the tissue expression profile of 33 GPCRs (27 GPCR-As and six GPCR-Bs) transcripts. These GPCRs were found to be widely expressed in different tissues. Similar to the expression profiles of neuropeptides, 20 of these putative GPCR-encoding transcripts were also detected in the ovary. This is the first study to establish the identify of neuropeptides and their GPCRs in P. trituberculatus, and provide information for further investigations into the effect of neuropeptides on the physiology and behavior of decapod crustaceans.

Electrophysiological Generators in Clinical Neurophysiology

2016 ◽  
pp. 31-34
Author(s):  
Terrence D. Lagerlund
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
The Body ◽  
Sweat Glands ◽  
Pathological Changes ◽  
Anatomical Structures ◽  
Disease States ◽  
Neurophysiological Studies ◽  
The Central Nervous System ◽  
Clinical Interest

The variety of clinical neurophysiological studies corresponds to a variety of structural generators in the body, including muscles, sweat glands, peripheral nerves, and various components of the central nervous system. Each structural generator may have associated with it several different types of physiological potential. This chapter reviews the generators of electrophysiological potentials in terms of basic cellular electrophysiology and the anatomical structures that generate electrophysiological potentials of clinical interest. Knowledge of the generators of the potentials recorded in clinical neurophysiological studies is helpful in understanding the characteristics and distribution of the recorded potentials and is the first step in correlating the alterations seen in disease states with the pathological changes demonstrated in the underlying generators.

scholarly journals Neuromedin U and Structural Analogs: An Overview of their Structure, Function and Selectivity

2020 ◽  
Vol 27 (39) ◽  
pp. 6744-6768 ◽  
Author(s):  
An De Prins ◽  
Ann Van Eeckhaut ◽  
Ilse Smolders ◽  
Dirk Tourwé ◽  
Steven Ballet
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Peptide Ligands ◽  
Peptide Sequence ◽  
Reduce Food Intake ◽  
Design And Synthesis ◽  
Physiological Processes ◽  
Obesity And Diabetes ◽  
The Central Nervous System ◽  
Treatment Of Obesity

The neuromedin U peptide sequence is highly conserved between various species. Neuromedin U is involved in a variety of physiological processes. It exerts its effects via two neuromedin U receptors, NMUR1 and NMUR2. These receptors are characterized by a distinct, yet complementary, tissue distribution with NMUR1 mostly found in the periphery, while NMUR2 is most abundant in the central nervous system. The capability of the neuropeptide to reduce food intake in rodents triggered the design and synthesis of a broad range of modified peptide ligands. The purpose of these ligands is to develop novel therapeutics which could be beneficial in the treatment of obesity and diabetes. Most compounds are derived either from the full-length neuromedin U sequence or are based on the truncated orthologs of this neuropeptide. Only a few non-peptidic ligands were developed. This review provides an overview on various neuromedin U analogs and mimetics that have been reported to date.

scholarly journals Encephalitic Arboviruses of Africa: Emergence, Clinical Presentation and Neuropathogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Robyn S. Klein
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Presentation ◽  
Current Knowledge ◽  
Memory Disorders ◽  
Neurologic Diseases ◽  
The Central Nervous System ◽  
Neurological Infections ◽  
Geographical Locations ◽  
Post Infectious

Many mosquito-borne viruses (arboviruses) are endemic in Africa, contributing to systemic and neurological infections in various geographical locations on the continent. While most arboviral infections do not lead to neuroinvasive diseases of the central nervous system, neurologic diseases caused by arboviruses include flaccid paralysis, meningitis, encephalitis, myelitis, encephalomyelitis, neuritis, and post-infectious autoimmune or memory disorders. Here we review endemic members of the Flaviviridae and Togaviridae families that cause neurologic infections, their neuropathogenesis and host neuroimmunological responses in Africa. We also discuss the potential for neuroimmune responses to aide in the development of new diagnostics and therapeutics, and current knowledge gaps to be addressed by arbovirus research.

Distribution of catecholamines in the sea scallop, Placopecten magellanicus

1998 ◽  
Vol 76 (7) ◽  
pp. 1254-1262 ◽  
Author(s):  
Stephanie A Smith ◽  
Janette Nason ◽  
Roger P Croll
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
High Performance ◽  
Present Report ◽  
Placopecten Magellanicus ◽  
Peripheral Tissues ◽  
Sea Scallop ◽  
Physiological Processes ◽  
Gill Filaments ◽  
The Central Nervous System

Catecholamines have previously been implicated in several important physiological processes in molluscs, including reproduction, respiration, and feeding. Much of the previous research has relied upon high-performance liquid chromatography to identify and quantify the various catecholamines and pharmacological experiments to investigate their actions. In the present report, we expand upon these studies by using histochemical techniques to investigate the distribution of catecholamine-containing cells and fibres in the central nervous system and peripheral tissues of the sea scallop, Placopecten magellanicus. Strong catecholaminergic staining was present in the somata and neuropil of all major central ganglia. Catecholamines were also abundantly stained in peripheral neurones and (or) fibres in several other tissues, including the labial palps, lips, intestine, gill filaments, foot, mantle, tentacles, and gonadal integument. It is concluded that catecholamines are widespread in the tissues of the scallop and could have potential neurotransmission roles in both the central nervous system and peripheral tissues of this species.

scholarly journals Rabies-Like Neuronal Inclusions Associated with a Neoplastic Reticulosis in a Dog

1974 ◽  
Vol 11 (1) ◽  
pp. 29-37 ◽  
Author(s):  
A. M. Cameron ◽  
J. D. Conroy
Keyword(s):  
Central Nervous System ◽  
Endoplasmic Reticulum ◽  
Nervous System ◽  
Purkinje Cells ◽  
Inclusion Bodies ◽  
Neurologic Diseases ◽  
Intracytoplasmic Inclusion ◽  
Eosinophilic Inclusion ◽  
The Central Nervous System ◽  
Intracytoplasmic Inclusion Bodies

Neoplastic reticulosis of the central nervous system was associated with intracytoplasmic inclusion bodies in Purkinje cells and neurons of several nuclei. These eosinophilic inclusion bodies were from round to crescentic and had a different location, structure, and cytochemistry than Negri bodies and inclusions of other canine neurologic diseases. The inclusions represent an aberration of rough endoplasmic reticulum and resemble the cytoplasmic laminar bodies of the lateral geniculate neurons of the cat.

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