Multi-scale, multi-modal analysis uncovers complex relationship at the brain tissue-implant neural interface: new emphasis on the biological interface

Dynamical behavior of the head during an impact is important for analyzing the induced local damage or diffuse damage in the brain tissue. We determine in the present study the natural frequencies and the modal shapes of the system of brain, cerebro-spinal fluid and skull. Two models are presented in this work: an elastic-acoustic model assuming a rigid skull and an elastic-acoustic-elastic model assuming a deformable skull. It is shown that natural frequencies and more significantly the modal shapes are strongly influenced by the interaction between solid phases (brain and skull) and the cerebro-spinal fluid.

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A Multi-Scale Finite Element Model for Shock Wave-Induced Axonal Brain Injury

ASME 2008 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2008-192342 ◽

2008 ◽

Cited By ~ 4

Author(s):

M. Sotudeh-Chafi ◽

N. Abolfathi ◽

A. Nick ◽

V. Dirisala ◽

G. Karami ◽

...

Keyword(s):

Shock Wave ◽

Brain Injury ◽

Shock Waves ◽

Brain Tissue ◽

Scale Model ◽

Micro Scale ◽

Multi Scale ◽

Injury Criteria ◽

Wave Induced ◽

The Brain

Traumatic brain injuries (TBIs) involve a significant portion of human injuries resulting from a wide range of civilian accidents as well as many military scenarios. Axonal damage is one of the most common and important pathologic features of traumatic brain injury. Axons become brittle when exposed to rapid deformations associated with brain trauma. Accordingly, rapid stretch of axons can damage the axonal cytoskeleton, resulting in a loss of elasticity and impairment of axoplasmic transport. Subsequent swelling of the axon occurs in discrete bulb formations or in elongated varicosities that accumulate organelles. Ultimately, swollen axons may become disconnected [1]. The shock waves generated by a blast, subject all the organs in the head to displacement, shearing and tearing forces. The brain is especially vulnerable to these forces — the fronts of compressed air waves cause rapid forward or backward movements of the head, so that the brain rattles against the inside of the skull. This can cause subdural hemorrhage and contusions. The forces exerted on the brain by shock waves are known to damage axons in the affected areas. This axonal damage begins within minutes of injury, and can continue for hours or days following the injury [2]. Shock waves are also known to damage the brain at the subcellular level, but exactly how remains unclear. Kato et al., [3] described the effects of a small controlled explosion on rats’ brain tissue. They found that high pressure shock waves led to contusions and hemorrhage in both cortical and subcortical brain regions. Based on their result, the threshold for shock wave-induced brain injury is speculated to be under 1 MPa. This is the first report to demonstrate the pressure-dependent effect of shock wave on the histological characteristics of brain tissue. An important step in understanding the primary blast injury mechanism due to explosion is to translate the global head loads to the loading conditions, and consequently damage, of the cells at the local level and to project cell level and tissue level injury criteria towards the level of the head. In order to reach this aim, we have developed a multi-scale non-linear finite element modeling to bridge the micro- and macroscopic scales and establish the connection between microstructure and effective behavior of brain tissue to develop acceptable injury threshold. Part of this effort has been focused on measuring the shock waves created from a blast, and studying the response of the brain model of a human head exposed to such an environment. The Arbitrary Lagrangian Eulerian (ALE) and Fluid/Solid Interactions (FSI) formulation have been used to model the brain-blast interactions. Another part has gone into developing a validated fiber-matrix based micro-scale model of a brain tissue to reproduce the effective response and to capturing local details of the tissue’s deformations causing axonal injury. The micro-model of the axon and matrix is characterized by a transversely isotropic viscoelastic material and the material model is formulated for numerical implementation. Model parameters are fit to experimental frequency response of the storage and loss modulus data obtained and determined using a genetic algorithm (GA) optimizing method. The results from macro-scale model are used in the micro-scale brain tissue to study the effective behavior of this tissue under injury-based loadings. The research involves the development of a tool providing a better understanding of the mechanical behavior of the brain tissue against blast loads and a rational multi-scale approach for driving injury criteria.

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Liquid Chromatography Analysis of Clozapine in Rat Brain Tissue, Using its Molecularly Imprinted Polymer after Administration of Toxic Dose of Drug and Lipid Emulsion Therapy

Current Pharmaceutical Analysis ◽

10.2174/1573412914666180111160741 ◽

2019 ◽

Vol 15 (3) ◽

pp. 251-257

Author(s):

Bahareh Sadat Yousefsani ◽

Seyed Ahmad Mohajeri ◽

Mohammad Moshiri ◽

Hossein Hosseinzadeh

Keyword(s):

Rat Brain ◽

Brain Tissue ◽

Molecularly Imprinted Polymer ◽

Lipid Emulsion ◽

Limit Of Detection ◽

Imprinted Polymer ◽

Toxic Dose ◽

Molecularly Imprinted ◽

The Brain ◽

Rat Brain Tissue

Background:Molecularly imprinted polymers (MIPs) are synthetic polymers that have a selective site for a given analyte, or a group of structurally related compounds, that make them ideal polymers to be used in separation processes.Objective:An optimized molecularly imprinted polymer was selected and applied for selective extraction and analysis of clozapine in rat brain tissue.Methods:A molecularly imprinted solid-phase extraction (MISPE) method was developed for preconcentration and cleanup of clozapine in rat brain samples before HPLC-UV analysis. The extraction and analytical process was calibrated in the range of 0.025-100 ppm. Clozapine recovery in this MISPE process was calculated between 99.40 and 102.96%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.003 and 0.025 ppm, respectively. Intra-day precision values for clozapine concentrations of 0.125 and 0.025 ppm were 5.30 and 3.55%, whereas inter-day precision values of these concentrations were 9.23 and 6.15%, respectively. In this study, the effect of lipid emulsion infusion in reducing the brain concentration of drug was also evaluated.Results:The data indicated that calibrated method was successfully applied for the analysis of clozapine in the real rat brain samples after administration of a toxic dose to animal. Finally, the efficacy of lipid emulsion therapy in reducing the brain tissue concentration of clozapine after toxic administration of drug was determined.Conclusion:The proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of clozapine in rat brain tissue.

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Safety profile of the transcription factor EB (TFEB)-based gene therapy through intracranial injection in mice

Translational Neuroscience ◽

10.1515/tnsci-2020-0132 ◽

2020 ◽

Vol 11 (1) ◽

pp. 241-250

Author(s):

Zhenyu Li ◽

Guangqian Ding ◽

Yudi Wang ◽

Zelong Zheng ◽

Jianping Lv

Keyword(s):

Gene Therapy ◽

Transcription Factor ◽

Neurodegenerative Diseases ◽

Brain Tissue ◽

Inflammatory Responses ◽

Tissue Samples ◽

Protein Levels ◽

Virus Serotype ◽

Transcription Factor Eb ◽

The Brain

AbstractTranscription factor EB (TFEB)-based gene therapy is a promising therapeutic strategy in treating neurodegenerative diseases by promoting autophagy/lysosome-mediated degradation and clearance of misfolded proteins that contribute to the pathogenesis of these diseases. However, recent findings have shown that TFEB has proinflammatory properties, raising the safety concerns about its clinical application. To investigate whether TFEB induces significant inflammatory responses in the brain, male C57BL/6 mice were injected with phosphate-buffered saline (PBS), adeno-associated virus serotype 8 (AAV8) vectors overexpressing mouse TFEB (pAAV8-CMV-mTFEB), or AAV8 vectors expressing green fluorescent proteins (GFPs) in the barrel cortex. The brain tissue samples were collected at 2 months after injection. Western blotting and immunofluorescence staining showed that mTFEB protein levels were significantly increased in the brain tissue samples of mice injected with mTFEB-overexpressing vectors compared with those injected with PBS or GFP-overexpressing vectors. pAAV8-CMV-mTFEB injection resulted in significant elevations in the mRNA and protein levels of lysosomal biogenesis indicators in the brain tissue samples. No significant changes were observed in the expressions of GFAP, Iba1, and proinflammation mediators in the pAAV8-CMV-mTFEB-injected brain compared with those in the control groups. Collectively, our results suggest that AAV8 successfully mediates mTFEB overexpression in the mouse brain without inducing apparent local inflammation, supporting the safety of TFEB-based gene therapy in treating neurodegenerative diseases.

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High-fat diet-induced obesity and impairment of brain neurotransmitter pool

Translational Neuroscience ◽

10.1515/tnsci-2020-0099 ◽

2020 ◽

Vol 11 (1) ◽

pp. 147-160

Author(s):

Ranyah Shaker M. Labban ◽

Hanan Alfawaz ◽

Ahmed T. Almnaizel ◽

Wail M. Hassan ◽

Ramesa Shafi Bhat ◽

...

Keyword(s):

Oxidative Stress ◽

Brain Tissue ◽

High Fat Diet ◽

Density Lipoprotein ◽

Obese Group ◽

Control Group ◽

High Fat ◽

Brain Neurotransmitter ◽

The Brain ◽

Lean Group

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.

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Aggregation-and-Attention Network for brain tumor segmentation

BMC Medical Imaging ◽

10.1186/s12880-021-00639-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chih-Wei Lin ◽

Yu Hong ◽

Jinfu Liu

Keyword(s):

Brain Tumor ◽

Semantic Information ◽

Spatial Relationship ◽

Tumor Segmentation ◽

Computer Assisted ◽

Brain Tumor Segmentation ◽

Attention Network ◽

Multi Scale ◽

Assisted Diagnosis ◽

The Brain

Abstract Background Glioma is a malignant brain tumor; its location is complex and is difficult to remove surgically. To diagnosis the brain tumor, doctors can precisely diagnose and localize the disease using medical images. However, the computer-assisted diagnosis for the brain tumor diagnosis is still the problem because the rough segmentation of the brain tumor makes the internal grade of the tumor incorrect. Methods In this paper, we proposed an Aggregation-and-Attention Network for brain tumor segmentation. The proposed network takes the U-Net as the backbone, aggregates multi-scale semantic information, and focuses on crucial information to perform brain tumor segmentation. To this end, we proposed an enhanced down-sampling module and Up-Sampling Layer to compensate for the information loss. The multi-scale connection module is to construct the multi-receptive semantic fusion between encoder and decoder. Furthermore, we designed a dual-attention fusion module that can extract and enhance the spatial relationship of magnetic resonance imaging and applied the strategy of deep supervision in different parts of the proposed network. Results Experimental results show that the performance of the proposed framework is the best on the BraTS2020 dataset, compared with the-state-of-art networks. The performance of the proposed framework surpasses all the comparison networks, and its average accuracies of the four indexes are 0.860, 0.885, 0.932, and 1.2325, respectively. Conclusions The framework and modules of the proposed framework are scientific and practical, which can extract and aggregate useful semantic information and enhance the ability of glioma segmentation.

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Effect of Xenon Treatment on Gene Expression in Brain Tissue after Traumatic Brain Injury in Rats

Brain Sciences ◽

10.3390/brainsci11070889 ◽

2021 ◽

Vol 11 (7) ◽

pp. 889

Author(s):

Anton D. Filev ◽

Denis N. Silachev ◽

Ivan A. Ryzhkov ◽

Konstantin N. Lapin ◽

Anastasiya S. Babkina ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Brain Tissue ◽

Target Genes ◽

Neural Function ◽

Stress Genes ◽

Expression Of Genes ◽

Delayed Recovery ◽

The Brain ◽

Lower Expression

The overactivation of inflammatory pathways and/or a deficiency of neuroplasticity may result in the delayed recovery of neural function in traumatic brain injury (TBI). A promising approach to protecting the brain tissue in TBI is xenon (Xe) treatment. However, xenon’s mechanisms of action remain poorly clarified. In this study, the early-onset expression of 91 target genes was investigated in the damaged and in the contralateral brain areas (sensorimotor cortex region) 6 and 24 h after injury in a TBI rat model. The expression of genes involved in inflammation, oxidation, antioxidation, neurogenesis and neuroplasticity, apoptosis, DNA repair, autophagy, and mitophagy was assessed. The animals inhaled a gas mixture containing xenon and oxygen (ϕXe = 70%; ϕO2 25–30% 60 min) 15–30 min after TBI. The data showed that, in the contralateral area, xenon treatment induced the expression of stress genes (Irf1, Hmox1, S100A8, and S100A9). In the damaged area, a trend towards lower expression of the inflammatory gene Irf1 was observed. Thus, our results suggest that xenon exerts a mild stressor effect in healthy brain tissue and has a tendency to decrease the inflammation following damage, which might contribute to reducing the damage and activating the early compensatory processes in the brain post-TBI.

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VI. On the comparative structure of the brain in rodents

Proceedings of the Royal Society of London ◽

10.1098/rspl.1881.0066 ◽

1882 ◽

Vol 33 (216-219) ◽

pp. 15-21

Keyword(s):

Olfactory Organ ◽

Cortical Surface ◽

Complex Relationship ◽

Comparative Structure ◽

The Subject ◽

The Brain

I have endeavoured in this abstract to summarise the results of my recent researches into the minute structure of the brain in the smaller Rodents. The pig and sheep, which were the subjects of my former memoir, possess a highly developed olfactory apparatus conjoined to a well convoluted cortical surface; but in the smaller animals now under consideration the surface of the hemispheres is almost perfectly smooth, while the olfactory organ, from its comparative size and complex relationship, has an important part to play in the architecture of the brain. Animals possessing the latter type of cerebrum have been classed together as the Osmatic Lissencéphales, in contradistinction to those which were the subject of my former enquiries, the Osmatic Gyren-céphales. My researches into the structure of the brain of prominent members of the former group, viz., the rabbit and rat, may be considered under two heads:— ( a .) The histology of the complete cortical envelope.

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Pyruvic acid as an intermediary metabolite in the brain tissue of avitaminous and normal pigeons

Biochemical Journal ◽

10.1042/bj0280916 ◽

1934 ◽

Vol 28 (3) ◽

pp. 916-925 ◽

Cited By ~ 55

Author(s):

Rudolph Albert Peters ◽

Robert Henry Stewart Thompson

Keyword(s):

Brain Tissue ◽

Pyruvic Acid ◽

Intermediary Metabolite ◽

The Brain

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EXPERIMENTS ON THE SURVIVAL OF THE FEBRILE HERPETIC AND ALLIED VIRUSES IN VITRO

Journal of Experimental Medicine ◽

10.1084/jem.39.4.533 ◽

1924 ◽

Vol 39 (4) ◽

pp. 533-542 ◽

Cited By ~ 4

Author(s):

James E. McCartney

Keyword(s):

Brain Tissue ◽

Secondary Infection ◽

The Body ◽

Herpes Viruses ◽

Encephalitis Lethargica ◽

Aerobic Conditions ◽

Maximum Period ◽

Suitable Technique ◽

The Brain

These studies fail to confirm the statements previously made that microorganisms of the class of the globoid bodies of poliomyelitis may be cultivated in the Smith-Noguchi medium from the so called virus of encephalitis lethargica. They show equally that the herpes virus does not multiply in this medium. The experiments indicate, moreover, that the medium is unfavorable to the survival of the virus, while ordinary broth under aerobic conditions is more favorable for maintaining the activity of both the encephalitic and the herpes viruses. Probably no multiplication of either takes place in the latter medium but merely a survival, and for a maximum period of 6 days in the broth itself, and 12 days in the fragment of brain tissue immersed in the broth. Finally, it has been shown that with a suitable technique the viruses can be passed from the brain of one rabbit to that of another through a long series without contamination with cocci or other common bacterial forms. Hence we regard all reports of the finding of ordinary bacteria in the brain of cases of epidemic or lethargic encephalitis as instances of mixed or secondary infection arising during life, or examples of postmortem invasion of the body, or of faulty technique at the autopsy.

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