Revisiting gene delivery to the brain: silencing and editing

2021 ◽  
Author(s):  
João Conniot ◽  
Sepehr Talebian ◽  
Susana Simões ◽  
Lino Ferreira ◽  
João Conde
Keyword(s):  
Gene Delivery ◽  
Brain Tumors ◽  
Neurodegenerative Disorders ◽  
Brain Diseases ◽  
Ischemic Brain ◽  
The Brain

Neurodegenerative disorders, ischemic brain diseases, and brain tumors are debilitating diseases that severely impact a person's life and could possibly lead to their demise if left untreated.

MR imaging in the diagnosis of brain tumors

1993 ◽  
Vol 74 (3) ◽  
pp. 180-184
Author(s):  
I. V. Klyushkin ◽  
R. F. Bakhtiozin ◽  
M. M. Ibatullin ◽  
I. R. Chuvashaev ◽  
V. I. Zinin ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Diagnostic Method ◽  
Associate Professor ◽  
Posterior Cranial Fossa ◽  
Brain Diseases ◽  
X Ray ◽  
Chief Physician ◽  
X Ray Computed ◽  
Cranial Fossa ◽  
The Brain

Diagnosing brain diseases is one of the most difficult tasks in medicine. For the exclusion or detection of brain tumors, MRI is a valuable modern diagnostic method. It allows you to clarify the localization of the neoplasm within the brain, its relation to the surrounding tissues, to determine the presence of concomitant cerebral edema, vasculature, the shape, size, nature and structure of the tumor. In this respect, the center (chief physician associate professor IV Klyushkin) M3 RT MRI significantly exceeds the capabilities of X-ray computed tomography, especially in the diagnosis of tumors of the posterior cranial fossa and basal localization.

Brain Drug Delivery: Overcoming the Blood-brain Barrier to Treat Tauopathies

2020 ◽  
Vol 26 (13) ◽  
pp. 1448-1465 ◽  
Author(s):  
Jozef Hanes ◽  
Eva Dobakova ◽  
Petra Majerova
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Neurodegenerative Disorders ◽  
Brain Barrier ◽  
Neuronal Function ◽  
Brain Drug Delivery ◽  
Naturally Occurring ◽  
Blood Brain ◽  
Traditional Approaches ◽  
The Brain

Tauopathies are neurodegenerative disorders characterized by the deposition of abnormal tau protein in the brain. The application of potentially effective therapeutics for their successful treatment is hampered by the presence of a naturally occurring brain protection layer called the blood-brain barrier (BBB). BBB represents one of the biggest challenges in the development of therapeutics for central nervous system (CNS) disorders, where sufficient BBB penetration is inevitable. BBB is a heavily restricting barrier regulating the movement of molecules, ions, and cells between the blood and the CNS to secure proper neuronal function and protect the CNS from dangerous substances and processes. Yet, these natural functions possessed by BBB represent a great hurdle for brain drug delivery. This review is concentrated on summarizing the available methods and approaches for effective therapeutics’ delivery through the BBB to treat neurodegenerative disorders with a focus on tauopathies. It describes the traditional approaches but also new nanotechnology strategies emerging with advanced medical techniques. Their limitations and benefits are discussed.

Role of Flavonoids in Neurodegenerative Disorders with Special Emphasis on Tangeritin

2019 ◽  
Vol 18 (8) ◽  
pp. 581-597 ◽  
Author(s):  
Ambreen Fatima ◽  
Yasir Hasan Siddique
Keyword(s):  
Medicinal Plants ◽  
Mechanism Of Action ◽  
Neurodegenerative Disorders ◽  
Treatment Strategies ◽  
Dietary Supplementation ◽  
Plant Polyphenols ◽  
Promising Candidate ◽  
Naturally Occurring ◽  
The Brain

Flavonoids are naturally occurring plant polyphenols found universally in all fruits, vegetables and medicinal plants. They have emerged as a promising candidate in the formulation of treatment strategies for various neurodegenerative disorders. The use of flavonoid rich plant extracts and food in dietary supplementation have shown favourable outcomes. The present review describes the types, properties and metabolism of flavonoids. Neuroprotective role of various flavonoids and the possible mechanism of action in the brain against the neurodegeneration have been described in detail with special emphasis on the tangeritin.

Brain Tumor Detection via Asymmetry Quantification across Mid Sagittal Plane

2020 ◽  
Vol 13 ◽  
Author(s):  
Shoaib Amin Banday ◽  
Mohammad Khalid Pandit
Keyword(s):  
Brain Tumor ◽  
Brain Tumors ◽  
Sagittal Plane ◽  
Early Stage ◽  
Imaging Techniques ◽  
Complex Structure ◽  
Magnetic Resonance Images ◽  
Absolute Difference ◽  
Brain Hemispheres ◽  
The Brain

Introduction: Brain tumor is among the major causes of morbidity and mortality rates worldwide. According to National Brain Tumor Foundation (NBTS), the death rate has nearly increased by as much as 300% over last couple of decades. Tumors can be categorized as benign (non-cancerous) and malignant (cancerous). The type of the brain tumor significantly depends on various factors like the site of its occurrence, its shape, the age of the subject etc. On the other hand, Computer Aided Detection (CAD) has been improving significantly in recent times. The concept, design and implementation of these systems ascend from fairly simple ones to computationally intense ones. For efficient and effective diagnosis and treatment plans in brain tumor studies, it is imperative that an abnormality is detected at an early stage as it provides a little more time for medical professionals to respond. The early detection of diseases has predominantly been possible because of medical imaging techniques developed from past many decades like CT, MRI, PET, SPECT, FMRI etc. The detection of brain tumors however, has always been a challenging task because of the complex structure of the brain, diverse tumor sizes and locations in the brain. Method: This paper proposes an algorithm that can detect the brain tumors in the presence of the Radio-Frequency (RF) inhomoginiety. The algorithm utilizes the Mid Sagittal Plane as a landmark point across which the asymmetry between the two brain hemispheres is estimated using various intensity and texture based parameters. Result: The results show the efficacy of the proposed method for the detection of the brain tumors with an acceptable detection rate. Conclusion: In this paper, we have calculated three textural features from the two hemispheres of the brain viz: Contrast (CON), Entropy (ENT) and Homogeneity (HOM) and three parameters viz: Root Mean Square Error (RMSE), Correlation Co-efficient (CC), and Integral of Absolute Difference (IAD) from the intensity distribution profiles of the two brain hemispheres to predict any presence of the pathology. First a Mid Sagittal Plane (MSP) is obtained on the Magnetic Resonance Images that virtually divides brain into two bilaterally symmetric hemispheres. The block wise texture asymmetry is estimated for these hemispheres using the above 6 parameters.

scholarly journals Beyond Oncological Hyperthermia: Physically Drivable Magnetic Nanobubbles as Novel Multipurpose Theranostic Carriers in the Central Nervous System

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2104 ◽  
Author(s):  
Eleonora Ficiarà ◽  
Shoeb Anwar Ansari ◽  
Monica Argenziano ◽  
Luigi Cangemi ◽  
Chiara Monge ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Tumors ◽  
Ad Hoc ◽  
Superparamagnetic Iron Oxide ◽  
Conventional Radiotherapy ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.

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 Laser interstitial thermotherapy (LITT) for the treatment of tumors of the brain and spine: a brief review

2021 ◽  
Vol 151 (3) ◽  
pp. 429-442
Author(s):  
Clark Chen ◽  
Ian Lee ◽  
Claudio Tatsui ◽  
Theresa Elder ◽  
Andrew E. Sloan
Keyword(s):  
Brain Tumors ◽  
Minimally Invasive ◽  
Radiation Necrosis ◽  
Spinal Metastasis ◽  
Clinical Approach ◽  
Invasive Treatment ◽  
Primary Indication ◽  
Interstitial Thermotherapy ◽  
The Brain

Abstract Introduction Laser Interstitial Thermotherapy (LITT; also known as Stereotactic Laser Ablation or SLA), is a minimally invasive treatment modality that has recently gained prominence in the treatment of malignant primary and metastatic brain tumors and radiation necrosis and studies for treatment of spinal metastasis has recently been reported. Methods Here we provide a brief literature review of the various contemporary uses for LITT and their reported outcomes. Results Historically, the primary indication for LITT has been for the treatment of recurrent glioblastoma (GBM). However, indications have continued to expand and now include gliomas of different grades, brain metastasis (BM), radiation necrosis (RN), other types of brain tumors as well as spine metastasis. LITT is emerging as a safe, reliable, minimally invasive clinical approach, particularly for deep seated, focal malignant brain tumors and radiation necrosis. The role of LITT for treatment of other types of tumors of the brain and for spine tumors appears to be evolving at a small number of centers. While the technology appears to be safe and increasingly utilized, there have been few prospective clinical trials and most published studies combine different pathologies in the same report. Conclusion Well-designed prospective trials will be required to firmly establish the role of LITT in the treatment of lesions of the brain and spine.

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 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 Human Monocytes Plasticity in Neurodegeneration

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 717
Author(s):  
Ilenia Savinetti ◽  
Angela Papagna ◽  
Maria Foti
Keyword(s):  
Neurodegenerative Disorders ◽  
Current Knowledge ◽  
Neurological Diseases ◽  
Surface Marker ◽  
First Line ◽  
Surface Marker Expression ◽  
Physiological Properties ◽  
Attractive Therapeutic Target ◽  
The Brain ◽  
Lateral Sclerosis

Monocytes play a crucial role in immunity and tissue homeostasis. They constitute the first line of defense during the inflammatory process, playing a role in the pathogenesis and progression of diseases, making them an attractive therapeutic target. They are heterogeneous in morphology and surface marker expression, which suggest different molecular and physiological properties. Recent evidences have demonstrated their ability to enter the brain, and, as a consequence, their hypothetical role in different neurodegenerative diseases. In this review, we will discuss the current knowledge about the correlation between monocyte dysregulation in the brain and/or in the periphery and neurological diseases in humans. Here we will focus on the most common neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis.

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