scholarly journals Infants’ cortex undergoes microstructural growth coupled with myelination during development

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Vaidehi S. Natu ◽  
Mona Rosenke ◽  
Hua Wu ◽  
Francesca R. Querdasi ◽  
Holly Kular ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Human Life ◽  
Quantitative Imaging ◽  
Tissue Growth ◽  
Early Infancy ◽  
Brain Functions ◽  
Quantitative Measurements ◽  
Visual Areas ◽  
Key Factor

AbstractDevelopment of cortical tissue during infancy is critical for the emergence of typical brain functions in cortex. However, how cortical microstructure develops during infancy remains unknown. We measured the longitudinal development of cortex from birth  to six months of age  using multimodal quantitative imaging of cortical microstructure. Here we show that infants’ cortex undergoes profound microstructural tissue growth during the first six months of human life. Comparison of postnatal to prenatal transcriptomic gene expression data demonstrates that myelination and synaptic processes are dominant contributors to this postnatal microstructural tissue growth. Using visual cortex as a model system, we find hierarchical microstructural growth: higher-level visual areas have less mature tissue at birth than earlier visual areas but grow at faster rates. This overturns the prominent view that visual areas that are most mature at birth develop fastest. Together, in vivo, longitudinal, and quantitative measurements, which we validated with ex vivo transcriptomic data, shed light on the rate, sequence, and biological mechanisms of developing cortical systems during early infancy. Importantly, our findings propose a hypothesis that cortical myelination is a key factor in cortical development during early infancy, which has important implications for diagnosis of neurodevelopmental disorders and delays in infants.

scholarly journals Effect of ethanol and cocaine on [11C]MPC-6827 uptake in SH-SY5Y cells

2021 ◽  
Author(s):  
Naresh Damuka ◽  
Miranda Orr ◽  
Paul W. Czoty ◽  
Jeffrey L. Weiner ◽  
Thomas J. Martin ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Ex Vivo ◽  
Neuroblastoma Cells ◽  
Proper Function ◽  
Brain Functions ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Vitro Binding

AbstractMicrotubules (MTs) are structural units in the cytoskeleton. In brain cells they are responsible for axonal transport, information processing, and signaling mechanisms. Proper function of these processes is critical for healthy brain functions. Alcohol and substance use disorders (AUD/SUDs) affects the function and organization of MTs in the brain, making them a potential neuroimaging marker to study the resulting impairment of overall neurobehavioral and cognitive processes. Our lab reported the first brain-penetrant MT-tracking Positron Emission Tomography (PET) ligand [11C]MPC-6827 and demonstrated its in vivo utility in rodents and non-human primates. To further explore the in vivo imaging potential of [11C]MPC-6827, we need to investigate its mechanism of action. Here, we report preliminary in vitro binding results in SH-SY5Y neuroblastoma cells exposed to ethanol (EtOH) or cocaine in combination with multiple agents that alter MT stability. EtOH and cocaine treatments increased MT stability and decreased free tubulin monomers. Our initial cell-binding assay demonstrated that [11C]MPC-6827 may have high affinity to free/unbound tubulin units. Consistent with this mechanism of action, we observed lower [11C]MPC-6827 uptake in SH-SY5Y cells after EtOH and cocaine treatments (e.g., fewer free tubulin units). We are currently performing in vivo PET imaging and ex vivo biodistribution studies in rodent and nonhuman primate models of AUD and SUDs and Alzheimer's disease.

An Innovative Ex Vivo Vascular Bioreactor as Comprehensive Tool to Study the Behavior of Native Blood Vessels Under Physiologically Relevant Conditions

2019 ◽  
Vol 2 (4) ◽  
Author(s):  
Noemi Vanerio ◽  
Marco Stijnen ◽  
Bas A. J. M. de Mol ◽  
Linda M. Kock
Keyword(s):  
Shear Stress ◽  
Blood Vessels ◽  
Ultrasound Imaging ◽  
Ex Vivo ◽  
Biological Response ◽  
Vessel Diameter ◽  
Tissue Growth ◽  
In Vivo Models

Abstract Ex vivo systems represent important models to study vascular biology and to test medical devices, combining the advantages of in vitro and in vivo models such as controllability of parameters and the presence of biological response, respectively. The aim of this study was to develop a comprehensive ex vivo vascular bioreactor to long-term culture and study the behavior of native blood vessels under physiologically relevant conditions. The system was designed to allow for physiological mechanical loading in terms of pulsatile hemodynamics, shear stress, and longitudinal prestretch and ultrasound imaging for vessel diameter and morphology evaluation. In this first experience, porcine carotid arteries (n = 4) from slaughterhouse animals were cultured in the platform for 10 days at physiological temperature, CO2 and humidity using medium with blood-mimicking viscosity, components, and stability of composition. As expected, a significant increase in vessel diameter was observed during culture. Flow rate was adjusted according to diameter values to reproduce and maintain physiological shear stress, while pressure was kept physiological. Ultrasound imaging showed that the morphology and structure of cultured arteries were comparable to in vivo. Histological analyses showed preserved endothelium and extracellular matrix and neointimal tissue growth over 10 days of culture. In conclusion, we have developed a comprehensive pulsatile system in which a native blood vessel can be cultured under physiological conditions. The present model represents a significant step toward ex vivo testing of vascular therapies, devices, drug interaction, and as basis for further model developments.

scholarly journals Asymptomatic Carriage of Group A Streptococcus Is Associated with Elimination of Capsule Production

2014 ◽  
Vol 82 (9) ◽  
pp. 3958-3967 ◽  
Author(s):  
Anthony R. Flores ◽  
Brittany E. Jewell ◽  
Randall J. Olsen ◽  
Samuel A. Shelburne ◽  
Nahuel Fittipaldi ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Group A Streptococcus ◽  
Ex Vivo ◽  
Human Subjects ◽  
Full Genome Sequencing ◽  
Isogenic Strain ◽  
Capsule Production ◽  
Key Factor ◽  
Group A

ABSTRACTHumans commonly carry pathogenic bacteria asymptomatically, but despite decades of study, the underlying molecular contributors remain poorly understood. Here, we show that a group A streptococcus carriage strain contains a frameshift mutation in thehasAgene resulting in loss of hyaluronic acid capsule biosynthesis. This mutation was repaired by allelic replacement, resulting in restoration of capsule production in the isogenic derivative strain. The “repaired” isogenic strain was significantly more virulent than the carriage strain in a mouse model of necrotizing fasciitis and had enhanced growthex vivoin human blood. Importantly, the repaired isogenic strain colonized the mouse oropharynx with significantly greater bacterial burden and had significantly reduced ability to internalize into cultured epithelial cells than the acapsular carriage strain. We conducted full-genome sequencing of 81 strains cultured serially from 19 epidemiologically unrelated human subjects and discovered the common theme that mutations negatively affecting capsule biosynthesis arisein vivoin thehasoperon. The significantly decreased capsule production is a key factor contributing to the molecular détente between pathogen and host. Our discoveries suggest a general model for bacterial pathogens in which mutations that downregulate or ablate virulence factor production contribute to carriage.

Design of an SMA Actuated Mechanotransductive Implant for Correcting Short Bowel Syndrome

2010 ◽  
Author(s):  
Brent Utter ◽  
Brian Barnes ◽  
Jonathan Luntz ◽  
Diann Brei ◽  
Daniel H. Teitelbaum ◽  
...  
Keyword(s):  
Short Bowel Syndrome ◽  
Mechanical Load ◽  
Medical Condition ◽  
Ex Vivo ◽  
The United States ◽  
Tissue Growth ◽  
Force Model ◽  
Short Bowel ◽  
Unique Shape

Short bowel syndrome is a serious medical condition afflicting an estimated 20,000 to 200,000 people in the United States with mortality rates as high as 40%, despite current treatments. Recent research on mechanotransduction, the process through which mechanical load induces tissue growth, has successfully demonstrated permanent growth of healthy, functional bowel in small animals. Unfortunately, the underlying technological approaches limit further research of growth under different load profiles and extension to safe clinical devices. This paper presents a fully implantable bowel extender which expands via a unique Shape Memory Alloy (SMA) driven ratcheting mechanism, measures the bowel tension and load, and enables studies of mechanotransductive bowel tissue growth where the displacement or load may be controlled wirelessly in real-time. The architecture and operation of the bowel extender is illustrated, focusing on the SMA driven ratcheting mechanism that incrementally expands the device. To help visualize the SMA wire and reset spring design, an alternative graphical method is outlined which transforms the SMA material curves into a Reset View based on predictions of the system forces. An analytical model predicts the ratchet mechanism force with tooth and pawl geometry selected based on packaging, load-bearing, and kinematic constraints. Force limits to maintain tissue health are established from ex vivo and in vivo porcine small bowel loading experiments. The Reset View methodology is applied to design a bowel extender prototype which is used to experimentally validate the ratchet force model. The functionality device is demonstrated, operating against loads much larger than specified, validating the device’s ability to enable new studies of mechanotransductive bowel growth in pigs.

scholarly journals Restoration of Visual Function and Cortical Connectivity After Ischemic Injury Through NeuroD1-Mediated Gene Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu Tang ◽  
Qiuyu Wu ◽  
Mang Gao ◽  
Esther Ryu ◽  
Zifei Pei ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Neuronal Loss ◽  
Ischemic Injury ◽  
Direct Conversion ◽  
Neuronal Population ◽  
Visual Responses ◽  
Brain Functions ◽  
Cortical Circuit ◽  
Visual Cortical

Neural circuits underlying brain functions are vulnerable to damage, including ischemic injury, leading to neuronal loss and gliosis. Recent technology of direct conversion of endogenous astrocytes into neurons in situ can simultaneously replenish the neuronal population and reverse the glial scar. However, whether these newly reprogrammed neurons undergo normal development, integrate into the existing neuronal circuit, and acquire functional properties specific for this circuit is not known. We investigated the effect of NeuroD1-mediated in vivo direct reprogramming on visual cortical circuit integration and functional recovery in a mouse model of ischemic injury. After performing electrophysiological extracellular recordings and two-photon calcium imaging of reprogrammed cells in vivo and mapping the synaptic connections formed onto these cells ex vivo, we discovered that NeuroD1 reprogrammed neurons were integrated into the cortical microcircuit and acquired direct visual responses. Furthermore, following visual experience, the reprogrammed neurons demonstrated maturation of orientation selectivity and functional connectivity. Our results show that NeuroD1-reprogrammed neurons can successfully develop and integrate into the visual cortical circuit leading to vision recovery after ischemic injury.

scholarly journals Latest Trends in Electrochemical Sensors for Neurotransmitters: A Review

Sensors ◽  
2019 ◽  
Vol 19 (9) ◽  
pp. 2037 ◽  
Author(s):  
Tavakolian-Ardakani ◽  
Hosu ◽  
Cristea ◽  
Mazloum-Ardakani ◽  
Marrazza
Keyword(s):  
Electrochemical Sensors ◽  
Ex Vivo ◽  
Analytical Techniques ◽  
Substantial Improvement ◽  
Robust Detection ◽  
Brain Functions ◽  
The Brain ◽  
Made In

Neurotransmitters are endogenous chemical messengers which play an important role in many of the brain functions, abnormal levels being correlated with physical, psychotic and neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease. Therefore, their sensitive and robust detection is of great clinical significance. Electrochemical methods have been intensively used in the last decades for neurotransmitter detection, outclassing more complicated analytical techniques such as conventional spectrophotometry, chromatography, fluorescence, flow injection, and capillary electrophoresis. In this manuscript, the most successful and promising electrochemical enzyme-free and enzymatic sensors for neurotransmitter detection are reviewed. Focusing on the activity of worldwide researchers mainly during the last ten years (2010–2019), without pretending to be exhaustive, we present an overview of the progress made in sensing strategies during this time. Particular emphasis is placed on nanostructured-based sensors, which show a substantial improvement of the analytical performances. This review also examines the progress made in biosensors for neurotransmitter measurements in vitro, in vivo and ex vivo.

scholarly journals BNO 1095, a Standardized Dry Extract from the Fruits of Vitex agnus-castus, Impairs Angiogenesis-related Endothelial Cell Functions In Vitro

Planta Medica ◽  
2021 ◽  
Author(s):  
Iris Bischoff-Kont ◽  
Laura Brabenec ◽  
Rebecca Ingelfinger ◽  
Bernhard Nausch ◽  
Robert Fürst
Keyword(s):  
Endothelial Cell ◽  
Ex Vivo ◽  
Collagen Gel ◽  
Tissue Growth ◽  
Endothelial Cell Proliferation ◽  
Dry Extract ◽  
Cell Functions ◽  
Agnus Castus

AbstractBNO 1095, a standardized dry extract from the fruits of Vitex agnus-castus, represents an approved herbal medicinal product for the treatment of premenstrual syndrome. Angiogenesis, the formation of new blood vessels from pre-existing capillaries, plays a major role in physiological situations, such as wound healing or tissue growth in female reproductive organs, but it is also of great importance in pathophysiological conditions such as chronic inflammatory diseases or cancer. Angiogenesis is a highly regulated multi-step process consisting of distinct key events that can be influenced pharmacologically. Few studies suggested anti-angiogenic actions of V. agnus-castus fruit extracts in in vivo and ex vivo models. Here, we provide for the first time profound in vitro data on BNO 1095-derived anti-angiogenic effects focusing on distinct angiogenesis-related endothelial cell functions that are inevitable for the process of new blood vessel formation. We found that V. agnus-castus extract significantly attenuated undirected and chemotactic migration of primary human endothelial cells. Moreover, the extract efficiently inhibited endothelial cell proliferation and reduced the formation of tube-like structures on Matrigel. Of note, the treatment of endothelial cell spheroids almost blocked endothelial sprouting in a 3D collagen gel. Our data present new and detailed insights into the anti-angiogenic actions of BNO 1095 and, therefore, suggest a novel scope of potential therapeutic applications of the extract for which these anti-angiogenic properties are required.

scholarly journals A Review on Toxicity and Challenges in Transferability of Surface-functionalized Metallic Nanoparticles from Animal Models to Humans

2021 ◽  
Author(s):  
Muhammad Arif Asghar ◽  
Rabia Ismail Yousuf ◽  
Muhammad Harris Shoaib ◽  
Muhammad Arif Asghar ◽  
Nazish Mumtaz
Keyword(s):  
Surface Functionalization ◽  
Metallic Nanoparticles ◽  
Ex Vivo ◽  
Human Life ◽  
Biological Properties ◽  
Biological Macromolecules ◽  
Biomedical Sciences ◽  
Optimum Selection

The unique size and surface morphology of nanoparticles (NPs) have substantially influenced all aspects of human life, making nanotechnology a novel and promising field for various applications in biomedical sciences. Metallic NPs have gained immense interest over the last few decades due to their promising optical, electrical, and biological properties. However, the aggregation and the toxic nature of these NPs have restricted their utilization in more optimized applications. The optimum selection of biopolymers and biological macromolecules for surface functionalization of metallic NPs will significantly improve their biological applicability and biocompatibility. The present mini-review attempts to stress the overview of recent strategies involved in surface functionalization of metallic NPs, their specific biomedical applications, and comparison of their in vitro, ex vivo, and in vivo toxicities with non-functionalized metallic NPs. In addition, this review also discusses the various challenges for metallic NPs to undergo human clinical trials.

scholarly journals In-vivo histology of iron and myelin in the brain using magnetic susceptibility source separation in MRI

2020 ◽  
Author(s):  
Hyeong-Geol Shin ◽  
Jingu Lee ◽  
Young Hyun Yun ◽  
Seong Ho Yoo ◽  
Jinhee Jang ◽  
...  
Keyword(s):  
Magnetic Susceptibility ◽  
Ex Vivo ◽  
Biophysical Model ◽  
Normal Brain ◽  
Brain Functions ◽  
Magnetic Resonance Imaging Mri ◽  
The Individual ◽  
Multiple Sclerosis Patients ◽  
The Brain

ABSTRACTObtaining a histological fingerprint from the in-vivo brain has been a long-standing target of magnetic resonance imaging (MRI). In particular, non-invasive imaging of iron and myelin, which are involved in normal brain functions and are histopathological hallmarks in a few neurodegenerative diseases, has practical utilities in neuroscience and medicine. Here, we propose a biophysical model that describes the individual contribution of iron and myelin to MRI signals via their difference in magnetic susceptibility (i.e., paramagnetic iron vs. diamagnetic myelin). Using this model, we develop a method, χ-separation, that generates the voxel-wise distributions of iron and myelin. The method is validated using computer simulation and phantom experiments, and applied to ex-vivo and in-vivo brains. The results delineate the well-known histological features of iron and myelin in the specimen (e.g., co-localization of iron and myelin in Gennari line), healthy volunteers (e.g., myelin-lacking and iron-rich pulvinar), and multiple sclerosis patients (e.g., demyelinated iron-rim lesion). This new in-vivo histology technology, taking less than 20 min, may serve as a practical tool for exploring the microstructural information of the brain.

scholarly journals Multimodal Detection of Dopamine by Sniffer Cells Expressing Genetically Encoded Fluorescence Sensors

2021 ◽  
Author(s):  
Carmen Klein Herenbrink ◽  
Jonatan Fullerton Stoier ◽  
William Dalseg Reith ◽  
Abeer Dagra ◽  
Miguel Alejandro Cuadrado Gregorek ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Striatal Slices ◽  
Brain Functions ◽  
Endogenous Dopamine ◽  
Dopamine Content ◽  
Neuropsychiatric Diseases ◽  
Sensor Properties ◽  
Dopamine Efflux

Dopamine serves an important role in supporting both locomotor control and higher brain functions such as motivation and learning. Dopaminergic dysfunction is implicated in an equally multidimensional spectrum of neurological and neuropsychiatric diseases. Extracellular dopamine levels are known to be tightly controlled by presynaptic dopamine transporters (DAT), which is also a main target of psychostimulants. Still, detailed data on dopamine dynamics in space and time is needed to fully understand how dopamine signals are encoded and translated into cellular and behavioral responses, and to uncover the pathological effects of dopamine-related diseases. The recently developed genetically encoded fluorescent dopamine sensors enable unprecedented monitoring of dopamine dynamics and have changed the field of in vivo dopamine recording. However, the potential of these sensors to be used for in vitro and ex vivo assays remains unexplored. Here, we demonstrate a generalizable blueprint for making dopamine 'sniffer' cells for multimodal detection of dopamine in vitro and ex vivo. We generated sniffer cell lines with inducible expression of six different dopamine sensors and performed a head-to-head comparison of sensor properties to guide users in sensor selection. In proof-of-principle experiments, we show how the sniffer cells can be applied to measure release of endogenous dopamine from cultured neurons and striatal slices, and for determining total dopamine content in striatal tissue. Furthermore, we use the sniffer cells to quantify DAT-mediated dopamine uptake, and AMPH-induced and constitutive dopamine efflux as a radiotracer free, high-throughput alternative to electrochemical- and radiotracer-based assays. Importantly, the sniffer cells framework can readily be applied to other transmitter systems for which the list of genetically encoded fluorescent sensors is rapidly growing.

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