scholarly journals Peptide Mediated Brain Delivery of Nano- and Submicroparticles: A Synergistic Approach

2018 ◽  
Vol 24 (13) ◽  
pp. 1366-1376 ◽  
Author(s):  
Mark McCully ◽  
Macarena Sanchez-Navarro ◽  
Meritxell Teixido ◽  
Ernest Giralt
Keyword(s):  
High Loading ◽  
Brain Diseases ◽  
Brain Delivery ◽  
Brain Disorders ◽  
Delivery Vehicle ◽  
Vehicle Type ◽  
Current State ◽  
Synergistic Approach ◽  
The Brain ◽  
Gain Access

The brain is a complex, regulated organ with a highly controlled access mechanism: The Blood-Brain Barrier (BBB). The selectivity of this barrier is a double-edged sword, being both its greatest strength and weakness. This weakness is evident when trying to target therapeutics against diseases within the brain. Diseases such as metastatic brain cancer have extremely poor prognosis due to the poor permeability of many therapeutics across the BBB. Peptides can be designed to target BBB receptors and gain access to the brain by transcytosis. These peptides (known as BBB-shuttles) can carry compounds, usually excluded from the brain, across the BBB. BBB-shuttles are limited by poor loading of therapeutics and degradation of the peptide and cargo. Likewise, nano- submicro- and microparticles can be fine-tuned to limit their degradation and with high loading of therapeutics. However, most nano- and microparticles’ core materials completely lack efficient targeting, with a few selected materials able to cross the BBB passively. Combining the selectivity of peptides with the high loading potential of nano-, microparticles offers an exciting strategy to develop novel, targeted therapeutics towards many brain disorders and diseases. Nevertheless, at present the field is diverse, in both scope and nomenclature, often with competing or contradictory names. In this review, we will try to address some of these issues and evaluate the current state of peptide mediated nano,-microparticle transport to the brain, analyzing delivery vehicle type and peptide design, the two key components that must act synergistically for optimal therapeutic impact.

scholarly journals ON MENTAL ILLNESS AND BROKEN BRAINS

Think ◽  
2021 ◽  
Vol 20 (58) ◽  
pp. 103-112
Author(s):  
Anneli Jefferson
Keyword(s):  
Mental Illness ◽  
Mental Disorders ◽  
Brain Cancer ◽  
World View ◽  
Brain Diseases ◽  
Brain Disorders ◽  
Empirical Question ◽  
The Brain

ABSTRACTWe often hear that certain mental disorders are disorders of the brain, but it is not clear what this claim amounts to. Does it mean that they are like classic brain diseases such as brain cancer? I argue that this is not the case for most mental disorders. Neither does the claim that all mental disorders are brain disorders follow from a materialist world-view. The only plausible way of understanding mental disorders as brain disorders is a fairly modest one, where we label brain differences we find in mental illness as pathological based on their link to mental dysfunction. How many mental disorders will turn out to be brain disorders on this understanding is an empirical question.

scholarly journals Improving In Vivo Brain Delivery of Monoclonal Antibody Using Novel Cyclic Peptides

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 568 ◽  
Author(s):  
Ulapane ◽  
Kopec ◽  
Siahaan
Keyword(s):  
Monoclonal Antibody ◽  
Blood Brain Barrier ◽  
Cyclic Peptides ◽  
Brain Diseases ◽  
Brain Delivery ◽  
Plasma Stability ◽  
The Novel ◽  
The Brain ◽  
Better Than

Many proteins can be used to treat brain diseases; however, the presence of the blood–brain barrier (BBB) creates an obstacle to delivering them into the brain. Previously, various molecules were delivered through the paracellular pathway of the BBB via its modulation, using ADTC5 and HAV6 peptides. This study goal was to design new cyclic peptides with N-to-C terminal cyclization for better plasma stability and modulation of the BBB. Cyclic HAVN1 and HAVN2 peptides were derived from a linear HAV6 peptide. Linear and N-to-C terminal cyclic ADTHAV peptides were designed by combining the sequences of ADTC5 and HAV6. These novel cyclic peptides were used to deliver an IRdye800CW-labeled IgG monoclonal antibody into the brain. Cyclic HAVN1 and HAVN2 peptides deliver IgG into the brain, while the parent linear HAV6 peptide does not. Cyclic and linear ADTHAV and ADTC5 peptides enhanced brain delivery of IgG mAb, in which cyclic ADTHAV peptide was better than linear ADTHAV (p = 0.07). Cyclic ADTHAV and ADTC5 influenced the distribution of IgG mAb in other organs while HAV6, HAVN1 and HAVN2 did not. In summary, the novel cyclic peptides are generally better BBB modulators than their linear counterparts for delivering IgG mAb into the brain.

Nanostructured Lipid Carriers (NLCs): Nose-to-Brain Delivery and Theranostic Application

2020 ◽  
Vol 21 (14) ◽  
pp. 1136-1143 ◽  
Author(s):  
Javed Ahmad ◽  
Md. Rizwanullah ◽  
Saima Amin ◽  
Musarrat Husain Warsi ◽  
Mohammad Zaki Ahmad ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Administration ◽  
Neurological Disorders ◽  
State Of The Art ◽  
Scientific Data ◽  
Nanostructured Lipid Carriers ◽  
Brain Delivery ◽  
Intranasal Route ◽  
Current State ◽  
The Brain

Background: Nanostructured lipid carriers (NLCs) are in high demand in the existing pharmaceutical domain due to its high versatility. It is the newer generation of lipid nanoparticulate systems having a solid matrix and greater stability at room temperature. Objective: To review the evidence related to the current state of the art of the NLCs system and its drug delivery perspectives to the brain. Methods: Scientific data search, review of the current state of the art and drug delivery perspectives to the brain for NLCs were undertaken to assess the applicability of NLCs in the management of neurological disorders through an intranasal route of drug administration Results: NLCs are designed to fulfill all the industrial needs like simple technology, low cost, scalability, and quantifications. Biodegradable and biocompatible lipids and surfactants used for NLCs have rendered them acceptable from regulatory perspectives as well. Apart from these, NLCs have unique properties of high drug payload, modulation of drug release profile, minimum drug expulsion during storage, and incorporation in various dosage forms like gel, creams, granules, pellets, powders for reconstitution and colloidal dispersion. Ease of surface- modification of NLCs enhances targeting efficiency and reduces systemic toxicity by providing site-specific delivery to the brain through the intranasal route of drug administration. Conclusion: The present review encompasses the in-depth discussion over the current state of the art of NLCs, nose-to-brain drug delivery perspectives, and its theranostic application as useful tools for better management of various neurological disorders. Further, pharmacokinetic consideration and toxicity concern is also discussed specifically for the NLCs system exploited in nose-to-brain delivery.

scholarly journals Histamine N-Methyltransferase in the Brain

2019 ◽  
Vol 20 (3) ◽  
pp. 737 ◽  
Author(s):  
Takeo Yoshikawa ◽  
Tadaho Nakamura ◽  
Kazuhiko Yanai
Keyword(s):  
High Specificity ◽  
Brain Diseases ◽  
Brain Disorders ◽  
Nucleotide Polymorphisms ◽  
Histamine Concentration ◽  
Brain Histamine ◽  
Brain Functions ◽  
Brain Barrier Permeability ◽  
The Central Nervous System ◽  
The Brain

Brain histamine is a neurotransmitter and regulates diverse physiological functions. Previous studies have shown the involvement of histamine depletion in several neurological disorders, indicating the importance of drug development targeting the brain histamine system. Histamine N-methyltransferase (HNMT) is a histamine-metabolising enzyme expressed in the brain. Although pharmacological studies using HNMT inhibitors have been conducted to reveal the direct involvement of HNMT in brain functions, HNMT inhibitors with high specificity and sufficient blood–brain barrier permeability have not been available until now. Recently, we have phenotyped Hnmt-deficient mice to elucidate the importance of HNMT in the central nervous system. Hnmt disruption resulted in a robust increase in brain histamine concentration, demonstrating the essential role of HNMT in the brain histamine system. Clinical studies have suggested that single nucleotide polymorphisms of the human HNMT gene are associated with several brain disorders such as Parkinson’s disease and attention deficit hyperactivity disorder. Postmortem studies also have indicated that HNMT expression is altered in human brain diseases. These findings emphasise that an increase in brain histamine levels by novel HNMT inhibitors could contribute to the improvement of brain disorders.

scholarly journals Human Brain Disorders: A Review

2020 ◽  
Vol 8 (1) ◽  
pp. 6-21
Author(s):  
Falaq Naz ◽  
Yasir Hasan Siddique
Keyword(s):  
Human Brain ◽  
Brain Structure ◽  
New Technology ◽  
Treatment Strategies ◽  
Brain Diseases ◽  
Brain Disorders ◽  
Ancient Greek ◽  
The Subject ◽  
The Brain ◽  
Structure And Functions

Background: Due to the stressful life, brain disorders are considered as a significant global healthcare problem. It has generated a great need for continuous research for understanding brain structure as well as functions in context to health and diseases. Scope and Approach: The structure and functions of the brain were questioned and studied since Ancient Greek times and led to the compilation of enormous information on the subject globally. With the advent of new technology, the researchers are able to discover the causes of brain diseases/disorders. Conclusion: In the present review, we have compiled various diseases and disorders related to the brain, along with their symptoms and the treatment strategies.

From many to one: Meditation and the plasticity of the predictive mind

2020 ◽  
Author(s):  
Ruben Laukkonen ◽  
Heleen A Slagter
Keyword(s):  
Cognitive Enhancement ◽  
The Self ◽  
Predictive Processing ◽  
Focused Attention ◽  
Conceptual Processing ◽  
Current State ◽  
Contemplative Science ◽  
Open Monitoring ◽  
Living Organisms ◽  
The Brain

How profoundly can humans change their own minds? In this paper we offer a unifying account of meditation under the predictive processing view of living organisms. We start from relatively simple axioms. First, the brain is an organ that serves to predict based on past experience, both phylogenetic and ontogenetic. Second, meditation serves to bring one closer to the here and now by disengaging from anticipatory processes. We propose that practicing meditation therefore gradually reduces predictive processing, in particular counterfactual cognition—the tendency to construct abstract and temporally deep representations—until all conceptual processing falls away. Our Many- to-One account also places three main styles of meditation (focused attention, open monitoring, and non-dual meditation) on a single continuum, where each technique progressively relinquishes increasingly engrained habits of prediction, including the self. This deconstruction can also make the above processes available to introspection, permitting certain insights into one’s mind. Our review suggests that our framework is consistent with the current state of empirical and (neuro)phenomenological evidence in contemplative science, and is ultimately illuminating about the plasticity of the predictive mind. It also serves to highlight that contemplative science can fruitfully go beyond cognitive enhancement, attention, and emotion regulation, to its more traditional goal of removing past conditioning and creating conditions for potentially profound insights. Experimental rigor, neurophenomenology, and no-report paradigms combined with neuroimaging are needed to further our understanding of how different styles of meditation affect predictive processing and the self, and the plasticity of the predictive mind more generally.

A new method to predict anomaly in brain network based on graph deep learning

2020 ◽  
Vol 31 (6) ◽  
pp. 681-689
Author(s):  
Jalal Mirakhorli ◽  
Hamidreza Amindavar ◽  
Mojgan Mirakhorli
Keyword(s):  
Deep Learning ◽  
Large Scale ◽  
Brain Plasticity ◽  
Brain Network ◽  
High Order ◽  
Brain Diseases ◽  
Simultaneous Occurrence ◽  
Generative Adversarial Network ◽  
The Brain ◽  
Brain Connections

AbstractFunctional magnetic resonance imaging a neuroimaging technique which is used in brain disorders and dysfunction studies, has been improved in recent years by mapping the topology of the brain connections, named connectopic mapping. Based on the fact that healthy and unhealthy brain regions and functions differ slightly, studying the complex topology of the functional and structural networks in the human brain is too complicated considering the growth of evaluation measures. One of the applications of irregular graph deep learning is to analyze the human cognitive functions related to the gene expression and related distributed spatial patterns. Since a variety of brain solutions can be dynamically held in the neuronal networks of the brain with different activity patterns and functional connectivity, both node-centric and graph-centric tasks are involved in this application. In this study, we used an individual generative model and high order graph analysis for the region of interest recognition areas of the brain with abnormal connection during performing certain tasks and resting-state or decompose irregular observations. Accordingly, a high order framework of Variational Graph Autoencoder with a Gaussian distributer was proposed in the paper to analyze the functional data in brain imaging studies in which Generative Adversarial Network is employed for optimizing the latent space in the process of learning strong non-rigid graphs among large scale data. Furthermore, the possible modes of correlations were distinguished in abnormal brain connections. Our goal was to find the degree of correlation between the affected regions and their simultaneous occurrence over time. We can take advantage of this to diagnose brain diseases or show the ability of the nervous system to modify brain topology at all angles and brain plasticity according to input stimuli. In this study, we particularly focused on Alzheimer’s disease.

scholarly journals Genomic Mosaicism Formed by Somatic Variation in the Aging and Diseased Brain

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1071
Author(s):  
Isabel Costantino ◽  
Juliet Nicodemus ◽  
Jerold Chun
Keyword(s):  
Dna Sequence ◽  
Technology Development ◽  
Copy Number Variations ◽  
Brain Cell ◽  
Brain Diseases ◽  
Multiple Forms ◽  
Somatic Variation ◽  
Dna Content Variation ◽  
Effects Of Aging ◽  
The Brain

Over the past 20 years, analyses of single brain cell genomes have revealed that the brain is composed of cells with myriad distinct genomes: the brain is a genomic mosaic, generated by a host of DNA sequence-altering processes that occur somatically and do not affect the germline. As such, these sequence changes are not heritable. Some processes appear to occur during neurogenesis, when cells are mitotic, whereas others may also function in post-mitotic cells. Here, we review multiple forms of DNA sequence alterations that have now been documented: aneuploidies and aneusomies, smaller copy number variations (CNVs), somatic repeat expansions, retrotransposons, genomic cDNAs (gencDNAs) associated with somatic gene recombination (SGR), and single nucleotide variations (SNVs). A catch-all term of DNA content variation (DCV) has also been used to describe the overall phenomenon, which can include multiple forms within a single cell’s genome. A requisite step in the analyses of genomic mosaicism is ongoing technology development, which is also discussed. Genomic mosaicism alters one of the most stable biological molecules, DNA, which may have many repercussions, ranging from normal functions including effects of aging, to creating dysfunction that occurs in neurodegenerative and other brain diseases, most of which show sporadic presentation, unlinked to causal, heritable genes.

scholarly journals The brain timewise: how timing shapes and supports brain function

2015 ◽  
Vol 370 (1668) ◽  
pp. 20140170 ◽  
Author(s):  
Riitta Hari ◽  
Lauri Parkkonen
Keyword(s):  
Human Brain ◽  
Brain Imaging ◽  
Brain Function ◽  
Temporal Dynamics ◽  
Generative Models ◽  
Network Activity ◽  
Brain Diseases ◽  
Specific Information ◽  
Non Invasive ◽  
The Brain

We discuss the importance of timing in brain function: how temporal dynamics of the world has left its traces in the brain during evolution and how we can monitor the dynamics of the human brain with non-invasive measurements. Accurate timing is important for the interplay of neurons, neuronal circuitries, brain areas and human individuals. In the human brain, multiple temporal integration windows are hierarchically organized, with temporal scales ranging from microseconds to tens and hundreds of milliseconds for perceptual, motor and cognitive functions, and up to minutes, hours and even months for hormonal and mood changes. Accurate timing is impaired in several brain diseases. From the current repertoire of non-invasive brain imaging methods, only magnetoencephalography (MEG) and scalp electroencephalography (EEG) provide millisecond time-resolution; our focus in this paper is on MEG. Since the introduction of high-density whole-scalp MEG/EEG coverage in the 1990s, the instrumentation has not changed drastically; yet, novel data analyses are advancing the field rapidly by shifting the focus from the mere pinpointing of activity hotspots to seeking stimulus- or task-specific information and to characterizing functional networks. During the next decades, we can expect increased spatial resolution and accuracy of the time-resolved brain imaging and better understanding of brain function, especially its temporal constraints, with the development of novel instrumentation and finer-grained, physiologically inspired generative models of local and network activity. Merging both spatial and temporal information with increasing accuracy and carrying out recordings in naturalistic conditions, including social interaction, will bring much new information about human brain function.

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