Metabolic Sex Dimorphism of the Brain at the Gene, Cell, and Tissue Level

ABSTRACTFinite element models are frequently used to simulate traumatic brain injuries. However, current models are unable to capture the progressive damage caused by repeated head trauma. In this work, we propose a method for computing the history-dependent mechanical damage of axonal fiber bundle tracts in the brain. Through the introduction of multiple damage models, we provide the ability to link consecutive head impact simulations, so that potential injury to the brain can be tracked over time. In addition, internal damage variables are used to degrade the mechanical response of each axonal fiber bundle element. As a result, the stiffness of the aggregate tissue decreases as damage evolves. To counteract this degenerative process, we have also introduced a preliminary healing model that reverses the accumulated damage, based on a user-specified healing duration. Using two detailed examples, we demonstrate that damage produces a significant decrease in fiber stress, which ultimately propagates to the tissue level and produces a measurable decrease in overall stiffness. These results suggest that damage modeling has the potential to enhance current brain simulation techniques and lead to new insights, especially in the study of repetitive head injuries.

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Mitigating the Consequences of Subconcussive Head Injuries

Annual Review of Biomedical Engineering ◽

10.1146/annurev-bioeng-091219-053447 ◽

2020 ◽

Vol 22 (1) ◽

pp. 387-407

Author(s):

Eric A. Nauman ◽

Thomas M. Talavage ◽

Paul S. Auerbach

Keyword(s):

Head Injury ◽

Clinical Diagnosis ◽

Head Injuries ◽

Tissue Level ◽

Clinical Neurology ◽

Subconcussive Injury ◽

History Of ◽

Tissue Alteration ◽

The Brain

Subconcussive head injury represents a pathophysiology that spans the expertise of both clinical neurology and biomechanical engineering. From both viewpoints, the terms injury and damage, presented without qualifiers, are synonymously taken to mean a tissue alteration that may be recoverable. For clinicians, concussion is evolving from a purely clinical diagnosis to one that requires objective measurement, to be achieved by biomedical engineers. Subconcussive injury is defined as subclinical pathophysiology in which underlying cellular- or tissue-level damage (here, to the brain) is not severe enough to present readily observable symptoms. Our concern is not whether an individual has a (clinically diagnosed) concussion, but rather, how much accumulative damage an individual can tolerate before they will experience long-term deficit(s) in neurological health. This concern leads us to look for the history of damage-inducing events, while evaluating multiple approaches for avoiding injury through reduction or prevention of the associated mechanically induced damage.

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A parametric model of the brain vascular system for estimation of the arterial input function (AIF) at the tissue level

NMR in Biomedicine ◽

10.1002/nbm.3695 ◽

2017 ◽

Vol 30 (5) ◽

pp. e3695 ◽

Cited By ~ 6

Author(s):

Siamak P. Nejad-Davarani ◽

Hassan Bagher-Ebadian ◽

James R. Ewing ◽

Douglas C. Noll ◽

Tom Mikkelsen ◽

...

Keyword(s):

Vascular System ◽

Arterial Input Function ◽

Input Function ◽

Tissue Level ◽

Parametric Model ◽

The Brain

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Symptomatic Carotid Artery Stenosis: Impairment of Cerebral Autoregulation Measured at the Brain Tissue Level with Arterial Spin-labeling MR Imaging

Radiology ◽

10.1148/radiol.10091262 ◽

2010 ◽

Vol 256 (1) ◽

pp. 201-208 ◽

Cited By ~ 50

Author(s):

Reinoud P. H. Bokkers ◽

Matthias J. P. van Osch ◽

H. Bart van der Worp ◽

Gert J. de Borst ◽

Willem P. T. M. Mali ◽

...

Keyword(s):

Carotid Artery ◽

Mr Imaging ◽

Brain Tissue ◽

Carotid Artery Stenosis ◽

Cerebral Autoregulation ◽

Arterial Spin Labeling ◽

Spin Labeling ◽

Tissue Level ◽

Symptomatic Carotid ◽

The Brain

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Subcellular localization of PKA catalytic subunits provides a basis for their distinct functions in the retina

10.1101/2021.05.17.444584 ◽

2021 ◽

Author(s):

Jinae N. Roa ◽

Yuliang Ma ◽

Zbigniew Mikulski ◽

Qianlan Xu ◽

Ronit Ilouz ◽

...

Keyword(s):

Subcellular Localization ◽

Ganglion Cells ◽

Photoreceptor Cells ◽

Tissue Level ◽

Retinal Ganglion ◽

Catalytic Subunits ◽

Photoreceptor Outer Segments ◽

Cone Cells ◽

The Brain ◽

Tissues Expression

PKA signaling is essential for numerous processes but the subcellular localization of specific PKA isoforms has yet to be explored comprehensively in tissues. Expression of the Cβ protein, in particular, has not been mapped previously at the tissue level. In this study we used retina as a window into PKA signaling in the brain and characterized localization of PKA Cα, Cβ, RIIα, and RIIβ subunits. Each subunit presented a distinct localization pattern. Cα and Cβ were localized in all tissue layers, while RIIα and RIIβ were enriched in the photoreceptor cells in contrast to the cell body and retinal portion of retinal ganglion cells. Only Cα was observed in photoreceptor outer segments and the cilia transition zone, while Cβ was localized primarily to mitochondria and was especially prominent in the ellipsoid of the cone cells. In contrast to Cα, Cβ also never colocalized with RIIα or RIIβ. Using BaseScope technology to track expression of the Cβ isoforms we find that Cβ4 and Cβ4ab are prominently expressed and, therefore, likely code for mitochondrial-Cβ proteins. Our data indicates that PKA subunits are functionally nonredundant in the retina and suggesting that Cβ might be important for mitochondrial-associated neurodegenerative diseases previously linked to PKA dysfunction.

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EXPERIMENTAL STUDY OF THE IMPACT OF LOW FLUORINE CONCENTRATIONS ON THE TISSUE LEVEL OF HSP FAMILY PROTEINS

Hygiene and Sanitation ◽

10.18821/0016-9900-2018-97-7-604-608 ◽

2018 ◽

Vol 97 (7) ◽

pp. 604-608

Author(s):

Anna G. Zhukova ◽

L. G. Gorokhova ◽

A. V. Kiseleva ◽

T. G. Sazontova ◽

N. N. Mikhailova

Keyword(s):

Toxic Effect ◽

White Male ◽

Antioxidant Properties ◽

Tissue Level ◽

Male Rats ◽

Laboratory Animals ◽

Heme Oxygenase 1 ◽

Sensitive Organ ◽

The Impact ◽

The Brain

Introduction. Fluoride in high concentrations has a toxic effect not only on bone tissue but also on the heart, liver, kidneys, and brain. In the implementation of the response to toxic doses of fluorine the proteins of the HSP family are involved regulating intracellular and tissue homeostasis under various stress effects. The toxic effect of high fluorine concentrations the mechanisms of which are disclosed in fluorosis can be realized and at a level significantly lower than a toxic one. In the literature, there is little data on the peculiarities of the effects of low fluorine concentrations at the tissue and cellular levels. The aim of the study. To investigate the impact of low fluorine concentrations on the tissue level of HSP family proteins in the brain and liver of laboratory animals. Material and methods. The experiments were carried out on 60 white male rats of the same age weighing 200-250 g. The rats were divided into 2 groups: the control and the group of the animals exposed to sodium fluoride (NaF) within 6 weeks (at a concentration of 10 mg/l corresponding to the daily fluorine dose of 1.2 mg/kg per body weight). We determined the level of inducible HSP72 and HSP32 (heme-oxygenase-1) referred to proteins of HSP family (Heat shock proteins), the activity of free radical processes and antioxidant enzymes (superoxide dismutase (SOD) and catalase) in the brain and liver tissues. Results. The important role of stress-inducible HSP72 protein in protecting the brain from the damage caused by the prolonged exposure to low fluorine concentrations was shown. In the liver, a protective role against fluoride exposure is played by the protein HSP32 with antioxidant properties. At the tissue level, the prolongation of the terms of the development of chronic fluoride intoxication with low fluorine concentrations was revealed. In the liver appeared to be the highly sensitive organ to the fluorine accumulation, the significant lesion was detected.

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Hamster organotypic modeling of SARS-CoV-2 lung and brainstem infection

Nature Communications ◽

10.1038/s41467-021-26096-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Marion Ferren ◽

Valérie Favède ◽

Didier Decimo ◽

Mathieu Iampietro ◽

Nicole A. P. Lieberman ◽

...

Keyword(s):

Immune Responses ◽

Viral Infection ◽

Tissue Level ◽

Innate Immune ◽

Innate Immune Responses ◽

Organotypic Cultures ◽

Neurological Sequelae ◽

Global Pandemic ◽

Rapid Modeling ◽

The Brain

AbstractSARS-CoV-2 has caused a global pandemic of COVID-19 since its emergence in December 2019. The infection causes a severe acute respiratory syndrome and may also spread to central nervous system leading to neurological sequelae. We have developed and characterized two new organotypic cultures from hamster brainstem and lung tissues that offer a unique opportunity to study the early steps of viral infection and screening antivirals. These models are not dedicated to investigate how the virus reaches the brain. However, they allow validating the early tropism of the virus in the lungs and demonstrating that SARS-CoV-2 could infect the brainstem and the cerebellum, mainly by targeting granular neurons. Viral infection induces specific interferon and innate immune responses with patterns specific to each organ, along with cell death by apoptosis, necroptosis, and pyroptosis. Overall, our data illustrate the potential of rapid modeling of complex tissue-level interactions during infection by a newly emerged virus.

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The Effects of Directionality of Blunt Impacts on Mechanical Response of the Brain

Volume 3: Biomedical and Biotechnology Engineering ◽

10.1115/imece2014-39338 ◽

2014 ◽

Cited By ~ 2

Author(s):

Hesam Sarvghad-Moghaddam ◽

Ghodrat Karami ◽

Mariusz Ziejewski

Keyword(s):

Shear Stress ◽

Mechanical Response ◽

Diffuse Axonal Injury ◽

Linear Acceleration ◽

Human Head ◽

Tissue Level ◽

Injury Criteria ◽

Local Shear ◽

The Brain ◽

Local Shear Stress

The intrinsic complexity of the human head and brain lies within the non-uniformity of their constitutive components in terms of shape, material, function, and tolerance. Due to this complexity, the directionality of impact, when the head is exposed to an assault, is a major concern as different responses are anticipated based on the location of impact. The main objective of the study was to show that while most studies propose the injury criteria as based on the kinematical parameters, the tissue-level brain features are more substantiated injury indicators. Accordingly, a finite element (FE) approach was employed to elucidate the injury-related behavior of the head for front, back, and side impacts against a rigid wall. To this end, a 50th percentile FE head-neck model, including most anatomical features, was used. The kinematics of the head in terms of the linear acceleration, as well as the biomechanical response of the brain at the tissue level in terms of intracranial pressure (ICP) and maximum local shear stress, were evaluated as the main injury criteria. Ls-Dyna, a transient, nonlinear, and explicit FE code, was employed to carry out all the simulations. To verify the influence of impact directionality, identical boundary conditions were enforced in all impact scenarios. While brain responses showed similar patterns in all three directions, different peak values were predicted. The highest peak values for the local shear stress, ICP gradient, and the center mass linear acceleration of brain were observed for the frontal impact. These threshold values are of great significance in predicting injuries such as diffuse axonal injury (DAI) resulting from the shear deformation of brain axons. It is believed that directionality considerations could greatly help to improve the design of protective headgears which are considered to be the most effective tools in mitigating a TBI.

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Prion-Like Propagation Mechanisms in Tauopathies and Traumatic Brain Injury: Challenges and Prospects

Biomolecules ◽

10.3390/biom10111487 ◽

2020 ◽

Vol 10 (11) ◽

pp. 1487

Author(s):

Hadeel Alyenbaawi ◽

W. Ted Allison ◽

Sue-Ann Mok

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Chronic Traumatic Encephalopathy ◽

Tissue Level ◽

Therapeutic Approaches ◽

Tau Pathology ◽

The Brain

The accumulation of tau protein in the form of filamentous aggregates is a hallmark of many neurodegenerative diseases such as Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE). These dementias share traumatic brain injury (TBI) as a prominent risk factor. Tau aggregates can transfer between cells and tissues in a “prion-like” manner, where they initiate the templated misfolding of normal tau molecules. This enables the spread of tau pathology to distinct parts of the brain. The evidence that tauopathies spread via prion-like mechanisms is considerable, but work detailing the mechanisms of spread has mostly used in vitro platforms that cannot fully reveal the tissue-level vectors or etiology of progression. We review these issues and then briefly use TBI and CTE as a case study to illustrate aspects of tauopathy that warrant further attention in vivo. These include seizures and sleep/wake disturbances, emphasizing the urgent need for improved animal models. Dissecting these mechanisms of tauopathy progression continues to provide fresh inspiration for the design of diagnostic and therapeutic approaches.

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