scholarly journals Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection

2020 ◽  
Vol 6 (30) ◽  
pp. eabb4429
Author(s):  
Feihe Ma ◽  
Liu Yang ◽  
Zhuorui Sun ◽  
Jinjin Chen ◽  
Xuehui Rui ◽  
...  
Keyword(s):  
Intravenous Injection ◽  
Brain Function ◽  
Antisense Oligonucleotides ◽  
Brain Delivery ◽  
Central Nervous System Diseases ◽  
Efficient Delivery ◽  
Delivery Platform ◽  
Or Gene ◽  
The Brain ◽  
Lipid Formulations

Safe and efficient delivery of blood-brain barrier (BBB)–impermeable cargos into the brain through intravenous injection remains a challenge. Here, we developed a previously unknown class of neurotransmitter–derived lipidoids (NT-lipidoids) as simple and effective carriers for enhanced brain delivery of several BBB-impermeable cargos. Doping the NT-lipidoids into BBB-impermeable lipid nanoparticles (LNPs) gave the LNPs the ability to cross the BBB. Using this brain delivery platform, we successfully delivered amphotericin B (AmB), antisense oligonucleotides (ASOs) against tau, and genome-editing fusion protein (−27)GFP-Cre recombinase into the mouse brain via systemic intravenous administration. We demonstrated that the NT-lipidoid formulation not only facilitates cargo crossing of the BBB, but also delivery of the cargo into neuronal cells for functional gene silencing or gene recombination. This class of brain delivery lipid formulations holds great potential in the treatment of central nervous system diseases or as a tool to study the brain function.

scholarly journals Perivascular and Perineural Pathways Involved in Brain Delivery and Distribution of Drugs after Intranasal Administration

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 598 ◽  
Author(s):  
Jeffrey J. Lochhead ◽  
Thomas P. Davis
Keyword(s):  
Current Evidence ◽  
Perivascular Spaces ◽  
Brain Delivery ◽  
Physiological Conditions ◽  
Routes Of Administration ◽  
Disease States ◽  
Efficient Delivery ◽  
The Central Nervous System ◽  
Trigeminal Nerves ◽  
The Brain

One of the most challenging aspects of treating disorders of the central nervous system (CNS) is the efficient delivery of drugs to their targets within the brain. Only a small fraction of drugs is able to cross the blood–brain barrier (BBB) under physiological conditions, and this observation has prompted investigation into the routes of administration that may potentially bypass the BBB and deliver drugs directly to the CNS. One such route is the intranasal (IN) route. Increasing evidence has suggested that intranasally-administered drugs are able to bypass the BBB and access the brain through anatomical pathways connecting the nasal cavity to the CNS. Though the exact mechanisms regulating the delivery of therapeutics following IN administration are not fully understood, current evidence suggests that the perineural and perivascular spaces of the olfactory and trigeminal nerves are involved in brain delivery and cerebral perivascular spaces are involved in widespread brain distribution. Here, we review evidence for these delivery and distribution pathways, and we address questions that should be resolved in order to optimize the IN route of administration as a viable strategy to treat CNS disease states.

Frontier concept of rabi chip for intelligent humanoid

2018 ◽  
Vol 1 (2) ◽  
Author(s):  
Preecha Yupapin ◽  
Amiri I. S. ◽  
Ali J. ◽  
Ponsuwancharoen N. ◽  
Youplao P.
Keyword(s):  
Human Brain ◽  
Brain Function ◽  
Rabi Oscillation ◽  
Liquid Core ◽  
Brain Surface ◽  
Dipole Oscillation ◽  
On Chip ◽  
The Brain ◽  
Robotic Applications ◽  
Atom System

The sequence of the human brain can be configured by the originated strongly coupling fields to a pair of the ionic substances(bio-cells) within the microtubules. From which the dipole oscillation begins and transports by the strong trapped force, which is known as a tweezer. The tweezers are the trapped polaritons, which are the electrical charges with information. They will be collected on the brain surface and transport via the liquid core guide wave, which is the mixture of blood content and water. The oscillation frequency is called the Rabi frequency, is formed by the two-level atom system. Our aim will manipulate the Rabi oscillation by an on-chip device, where the quantum outputs may help to form the realistic human brain function for humanoid robotic applications.

Finding Community of Brain Networks Based on Neighbor Index and DPSO with Dynamic Crossover

2020 ◽  
Vol 15 (4) ◽  
pp. 287-299
Author(s):  
Jie Zhang ◽  
Junhong Feng ◽  
Fang-Xiang Wu
Keyword(s):  
Brain Function ◽  
Brain Networks ◽  
Discrete Particle Swarm Optimization ◽  
Mri Brain ◽  
Mutation Operators ◽  
Neural Unit ◽  
Crossover And Mutation ◽  
The Brain ◽  
Index Table ◽  
Dynamic Crossover

Background: : The brain networks can provide us an effective way to analyze brain function and brain disease detection. In brain networks, there exist some import neural unit modules, which contain meaningful biological insights. Objective:: Therefore, we need to find the optimal neural unit modules effectively and efficiently. Method:: In this study, we propose a novel algorithm to find community modules of brain networks by combining Neighbor Index and Discrete Particle Swarm Optimization (DPSO) with dynamic crossover, abbreviated as NIDPSO. The differences between this study and the existing ones lie in that NIDPSO is proposed first to find community modules of brain networks, and dose not need to predefine and preestimate the number of communities in advance. Results: : We generate a neighbor index table to alleviate and eliminate ineffective searches and design a novel coding by which we can determine the community without computing the distances amongst vertices in brain networks. Furthermore, dynamic crossover and mutation operators are designed to modify NIDPSO so as to alleviate the drawback of premature convergence in DPSO. Conclusion: The numerical results performing on several resting-state functional MRI brain networks demonstrate that NIDPSO outperforms or is comparable with other competing methods in terms of modularity, coverage and conductance metrics.

Neuroethics

2017 ◽  
Keyword(s):  
Brain Function ◽  
Ethical Issues ◽  
Wearable Technologies ◽  
Definition Of Death ◽  
Populations At Risk ◽  
The Future ◽  
Aging Adults ◽  
Definition Of ◽  
The Brain ◽  
New Criteria

We have new answers to how the brain works and tools which can now monitor and manipulate brain function. Rapid advances in neuroscience raise critical questions with which society must grapple. What new balances must be struck between diagnosis and prediction, and invasive and noninvasive interventions? Are new criteria needed for the clinical definition of death in cases where individuals are eligible for organ donation? How will new mobile and wearable technologies affect the future of growing children and aging adults? To what extent is society responsible for protecting populations at risk from environmental neurotoxins? As data from emerging technologies converge and are made available on public databases, what frameworks and policies will maximize benefits while ensuring privacy of health information? And how can people and communities with different values and perspectives be maximally engaged in these important questions? Neuroethics: Anticipating the Future is written by scholars from diverse disciplines—neurology and neuroscience, ethics and law, public health, sociology, and philosophy. With its forward-looking insights and considerations for the future, the book examines the most pressing current ethical issues.

Implantable neural interfaces

2018 ◽  
Author(s):  
Stefano Vassanelli
Keyword(s):  
Brain Function ◽  
Large Scale ◽  
Ionic Channels ◽  
Patch Clamp Technique ◽  
Advantages And Disadvantages ◽  
Optogenetic Stimulation ◽  
Physical Interfaces ◽  
The Brain

Establishing direct communication with the brain through physical interfaces is a fundamental strategy to investigate brain function. Starting with the patch-clamp technique in the seventies, neuroscience has moved from detailed characterization of ionic channels to the analysis of single neurons and, more recently, microcircuits in brain neuronal networks. Development of new biohybrid probes with electrodes for recording and stimulating neurons in the living animal is a natural consequence of this trend. The recent introduction of optogenetic stimulation and advanced high-resolution large-scale electrical recording approaches demonstrates this need. Brain implants for real-time neurophysiology are also opening new avenues for neuroprosthetics to restore brain function after injury or in neurological disorders. This chapter provides an overview on existing and emergent neurophysiology technologies with particular focus on those intended to interface neuronal microcircuits in vivo. Chemical, electrical, and optogenetic-based interfaces are presented, with an analysis of advantages and disadvantages of the different technical approaches.

scholarly journals Aquaporin-1 and aquaporin-9 gene variations in sudden infant death syndrome

2021 ◽  
Author(s):  
Siri Hauge Opdal ◽  
Linda Ferrante ◽  
Torleiv Ole Rognum ◽  
Arne Stray-Pedersen
Keyword(s):  
Sudden Infant Death Syndrome ◽  
Infant Death ◽  
Brain Function ◽  
Sudden Infant Death ◽  
Sudden Infant ◽  
Unexpected Death ◽  
Aquaporin 9 ◽  
Genes Encoding ◽  
External Risk ◽  
The Brain

AbstractSeveral studies have indicated that a vulnerability in the development and regulation of brain function is involved in sudden infant death syndrome (SIDS). The aim of this study was to investigate the genes encoding the brain aquaporins (AQPs) AQP1 and AQP9 in SIDS. The hypothesis was that specific variants of these genes are part of the genetic vulnerability predisposing infants to sudden unexpected death. The study included 168 SIDS cases with a median age of 15.5 (range 2–52) weeks and 372 adolescent/adult deceased controls with a median age of 44 (range 11–91) years. In the AQP1 gene, the rs17159702 CC/CT genotypes were found to be associated with SIDS (p = 0.02). In the AQP9 gene, the combination of a TT genotype of rs8042354, rs2292711 and rs13329178 was more frequent in SIDS cases than in controls (p = 0.03). In the SIDS group, an association was found between genetic variations in the AQP1 gene and maternal smoking and between the 3xTT combination in the AQP9 gene and being found lifeless in a prone position. In conclusion, this study adds further evidence to the involvement of brain aquaporins in SIDS, suggesting that specific variants of AQP genes constitute a genetic predisposition, making the infant vulnerable to sudden death together with external risk factors and probably other genetic factors.

scholarly journals Expression Analysis of Zinc Transporters in Nervous Tissue Cells Reveals Neuronal and Synaptic Localization of ZIP4

2021 ◽  
Vol 22 (9) ◽  
pp. 4511
Author(s):  
Chiara A. De Benedictis ◽  
Claudia Haffke ◽  
Simone Hagmeyer ◽  
Ann Katrin Sauer ◽  
Andreas M. Grabrucker
Keyword(s):  
Brain Function ◽  
Zinc Homeostasis ◽  
Zinc Transporters ◽  
Excitatory Synapses ◽  
Short Term ◽  
Synaptic Localization ◽  
Zinc Levels ◽  
Rat Astrocyte ◽  
Cellular Zinc ◽  
The Brain

In the last years, research has shown that zinc ions play an essential role in the physiology of brain function. Zinc acts as a potent neuromodulatory agent and signaling ions, regulating healthy brain development and the function of both neurons and glial cells. Therefore, the concentration of zinc within the brain and its cells is tightly controlled. Zinc transporters are key regulators of (extra-) cellular zinc levels, and deregulation of zinc homeostasis and zinc transporters has been associated with neurodegenerative and neuropsychiatric disorders. However, to date, the presence of specific family members and their subcellular localization within brain cells have not been investigated in detail. Here, we analyzed the expression of all zinc transporters (ZnTs) and Irt-like proteins (ZIPs) in the rat brain. We further used primary rat neurons and rat astrocyte cell lines to differentiate between the expression found in neurons or astrocytes or both. We identified ZIP4 expressed in astrocytes but significantly more so in neurons, a finding that has not been reported previously. In neurons, ZIP4 is localized to synapses and found in a complex with major postsynaptic scaffold proteins of excitatory synapses. Synaptic ZIP4 reacts to short-term fluctuations in local zinc levels. We conclude that ZIP4 may have a so-far undescribed functional role at excitatory postsynapses.

scholarly journals Systemic AAV6-synapsin-GFP administration results in lower liver biodistribution, compared to AAV1&2 and AAV9, with neuronal expression following ultrasound-mediated brain delivery

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danielle Weber-Adrian ◽  
Rikke Hahn Kofoed ◽  
Joseph Silburt ◽  
Zeinab Noroozian ◽  
Kairavi Shah ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Intravenous Injection ◽  
Viral Vectors ◽  
Focused Ultrasound ◽  
Fluorescent Protein ◽  
Gfp Expression ◽  
Peripheral Organs ◽  
Neuronal Expression ◽  
Green Fluorescent ◽  
The Brain

AbstractNon-surgical gene delivery to the brain can be achieved following intravenous injection of viral vectors coupled with transcranial MRI-guided focused ultrasound (MRIgFUS) to temporarily and locally permeabilize the blood–brain barrier. Vector and promoter selection can provide neuronal expression in the brain, while limiting biodistribution and expression in peripheral organs. To date, the biodistribution of adeno-associated viruses (AAVs) within peripheral organs had not been quantified following intravenous injection and MRIgFUS delivery to the brain. We evaluated the quantity of viral DNA from the serotypes AAV9, AAV6, and a mosaic AAV1&2, expressing green fluorescent protein (GFP) under the neuron-specific synapsin promoter (syn). AAVs were administered intravenously during MRIgFUS targeting to the striatum and hippocampus in mice. The syn promoter led to undetectable levels of GFP expression in peripheral organs. In the liver, the biodistribution of AAV9 and AAV1&2 was 12.9- and 4.4-fold higher, respectively, compared to AAV6. The percentage of GFP-positive neurons in the FUS-targeted areas of the brain was comparable for AAV6-syn-GFP and AAV1&2-syn-GFP. In summary, MRIgFUS-mediated gene delivery with AAV6-syn-GFP had lower off-target biodistribution in the liver compared to AAV9 and AAV1&2, while providing neuronal GFP expression in the striatum and hippocampus.

scholarly journals In the nose or on the tongue? Contrasting motivational effects of oral and intranasal oxytocin on arousal and reward during social processing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juan Kou ◽  
Chunmei Lan ◽  
Yingying Zhang ◽  
Qianqian Wang ◽  
Feng Zhou ◽  
...  
Keyword(s):  
Brain Function ◽  
Intranasal Administration ◽  
Emotional Cues ◽  
Beneficial Effects ◽  
Social Processing ◽  
Concentration Changes ◽  
Brain Reward ◽  
Male Subjects ◽  
The Brain ◽  
Potential Therapeutic Intervention

AbstractIntranasal oxytocin exerts wide-ranging effects on socioemotional behavior and is proposed as a potential therapeutic intervention in psychiatric disorders. However, following intranasal administration, oxytocin could penetrate directly into the brain or influence its activity via increased peripheral concentrations crossing the blood–brain barrier or influencing vagal projections. In the current randomized, placebo-controlled, pharmaco-imaging clinical trial we investigated effects of 24IU oral (lingual) oxytocin spray, restricting it to peripherally mediated blood-borne and vagal effects, on responses to face emotions in 80 male subjects and compared them with 138 subjects treated intranasally with 24IU. Oral, but not intranasal oxytocin administration increased both arousal ratings for faces and associated brain reward responses, the latter being partially mediated by blood concentration changes. Furthermore, while oral oxytocin increased amygdala and arousal responses to face emotions, after intranasal administration they were decreased. Thus, oxytocin can produce markedly contrasting motivational effects in relation to socioemotional cues when it influences brain function via different routes. These findings have important implications for future therapeutic use since administering oxytocin orally may be both easier and have potentially stronger beneficial effects by enhancing responses to emotional cues and increasing their associated reward.

scholarly journals Evaluation of the Lambs’ State of Consciousness Signs during Halal and Traditional Slaughtering

Agriculture ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 557
Author(s):  
Roberta Barrasso ◽  
Vincenzo Tufarelli ◽  
Edmondo Ceci ◽  
Francesco Luposella ◽  
Giancarlo Bozzo
Keyword(s):  
Electric Current ◽  
Brain Function ◽  
Traditional Method ◽  
Time Intervals ◽  
Corneal Reflex ◽  
Group A ◽  
Group B ◽  
The Brain

The aim of this study was to evaluate the persistence of two signs of consciousness (rhythmic breathing and corneal reflex) in lambs slaughtered according to the traditional method and Halal ritual rite. A total of 240 lambs were examined and divided into two equal groups (n = 120 each). Lambs of group A were subjected to the stunning phase by the action of an electric current on the brain, while lambs of group B were slaughtered according to the religious Halal method without prior stunning. Rhythmic breathing (RB) and corneal reflex (CR) were used as indicators of prolonged brain function, and their evaluation was carried out by the operators in three subsequent steps at 15 s, 30 s, and 90 s post-bleeding, respectively. The stunning of the lambs reduced the animal’s state of consciousness and, consequently, reduced suffering, pain, and distress. Indeed, the lambs of group B showed longer duration consciousness than the animals stunned by electrodes. The permanence of the reflexes in Halal slaughter could be reduced by introducing a reversible stunning method to make the animal temporarily unconscious. Moreover, given that our results revealed consciousness also after 90 s post-cut, the assessment of the animal’s state of consciousness in wider time intervals than those commonly used is recommended.

Sign in / Sign up

Export Citation Format

Share Document