Reorganization of syntactic processing following left-hemisphere brain damage: does right-hemisphere activity preserve function?

PubMed

Tyler, Lorraine K; Wright, Paul; Randall, Billi; Marslen-Wilson, William D; Stamatakis, Emmanuel A

2010-11-01

The extent to which the human brain shows evidence of functional plasticity across the lifespan has been addressed in the context of pathological brain changes and, more recently, of the changes that take place during healthy ageing. Here we examine the potential for plasticity by asking whether a strongly left-lateralized system can successfully reorganize to the right-hemisphere following left-hemisphere brain damage. To do this, we focus on syntax, a key linguistic function considered to be strongly left-lateralized, combining measures of tissue integrity, neural activation and behavioural performance. In a functional neuroimaging study participants heard spoken sentences that differentially loaded on syntactic and semantic information. While healthy controls activated a left-hemisphere network of correlated activity including Brodmann areas 45/47 and posterior middle temporal gyrus during syntactic processing, patients activated Brodmann areas 45/47 bilaterally and right middle temporal gyrus. However, voxel-based morphometry analyses showed that only tissue integrity in left Brodmann areas 45/47 was correlated with activity and performance; poor tissue integrity in left Brodmann area 45 was associated with reduced functional activity and increased syntactic deficits. Activity in the right-hemisphere was not correlated with damage in the left-hemisphere or with performance. Reduced neural integrity in the left-hemisphere through brain damage or healthy ageing results in increased right-hemisphere activation in homologous regions to those left-hemisphere regions typically involved in the young. However, these regions do not support the same linguistic functions as those in the left-hemisphere and only indirectly contribute to preserved syntactic capacity. This establishes the unique role of the left hemisphere in syntax, a core component in human language.

The NSW Brain Tissue Resource Centre: Banking for Alcohol and Major Neuropsychiatric Disorders Research

PubMed Central

Sutherland, G.T.; Sheedy, D.; Stevens, J.; McCrossin, T.; Smith, C.C.; van Roijen, M.; Kril, J.J.

2016-01-01

The New South Wales Brain Tissue Resource Centre (NSWBTRC) at the University of Sydney (Australia) is an established human brain bank providing tissue to the neuroscience research community for investigations on alcohol-related brain damage and major psychiatric illnesses such as schizophrenia. The NSWBTRC relies on wide community engagement to encourage those with and without neuropsychiatric illness to consent to donation through its allied research programs. The subsequent provision of high-quality samples relies on standardized operational protocols, associated clinical data, quality control measures, integrated information systems, robust infrastructure, and governance. These processes are continually augmented to complement the changes in internal and external governance as well as the complexity and diversity of advanced investigation techniques. This report provides an overview of the dynamic process of brain banking and discusses the challenges of meeting the future needs of researchers, including synchronicity with other disease-focus collections. PMID:27139235

Phenotypic Integration of Neurocranium and Brain

PubMed Central

RICHTSMEIER, JOAN T.; ALDRIDGE, KRISTINA; DeLEON, VALERIE B.; PANCHAL, JAYESH; KANE, ALEX A.; MARSH, JEFFREY L.; YAN, PENG; COLE, THEODORE M.

2009-01-01

Evolutionary history of Mammalia provides strong evidence that the morphology of skull and brain change jointly in evolution. Formation and development of brain and skull co-occur and are dependent upon a series of morphogenetic and patterning processes driven by genes and their regulatory programs. Our current concept of skull and brain as separate tissues results in distinct analyses of these tissues by most researchers. In this study, we use 3D computed tomography and magnetic resonance images of pediatric individuals diagnosed with premature closure of cranial sutures (craniosynostosis) to investigate phenotypic relationships between the brain and skull. It has been demonstrated previously that the skull and brain acquire characteristic dysmorphologies in isolated craniosynostosis, but relatively little is known of the developmental interactions that produce these anomalies. Our comparative analysis of phenotypic integration of brain and skull in premature closure of the sagittal and the right coronal sutures demonstrates that brain and skull are strongly integrated and that the significant differences in patterns of association do not occur local to the prematurely closed suture. We posit that the current focus on the suture as the basis for this condition may identify a proximate, but not the ultimate cause for these conditions. Given that premature suture closure reduces the number of cranial bones, and that a persistent loss of skull bones is demonstrated over the approximately 150 million years of synapsid evolution, craniosynostosis may serve as an informative model for evolution of the mammalian skull. PMID:16526048

Phenotypic integration of neurocranium and brain.

PubMed

Richtsmeier, Joan T; Aldridge, Kristina; DeLeon, Valerie B; Panchal, Jayesh; Kane, Alex A; Marsh, Jeffrey L; Yan, Peng; Cole, Theodore M

2006-07-15

Evolutionary history of Mammalia provides strong evidence that the morphology of skull and brain change jointly in evolution. Formation and development of brain and skull co-occur and are dependent upon a series of morphogenetic and patterning processes driven by genes and their regulatory programs. Our current concept of skull and brain as separate tissues results in distinct analyses of these tissues by most researchers. In this study, we use 3D computed tomography and magnetic resonance images of pediatric individuals diagnosed with premature closure of cranial sutures (craniosynostosis) to investigate phenotypic relationships between the brain and skull. It has been demonstrated previously that the skull and brain acquire characteristic dysmorphologies in isolated craniosynostosis, but relatively little is known of the developmental interactions that produce these anomalies. Our comparative analysis of phenotypic integration of brain and skull in premature closure of the sagittal and the right coronal sutures demonstrates that brain and skull are strongly integrated and that the significant differences in patterns of association do not occur local to the prematurely closed suture. We posit that the current focus on the suture as the basis for this condition may identify a proximate, but not the ultimate cause for these conditions. Given that premature suture closure reduces the number of cranial bones, and that a persistent loss of skull bones is demonstrated over the approximately 150 million years of synapsid evolution, craniosynostosis may serve as an informative model for evolution of the mammalian skull. Copyright 2006 Wiley-Liss, Inc.

Frozen tissue preparation for high-resolution multiplex histological analyses of human brain specimens.

PubMed

Shao, Fangjie; Jiang, Wenhong; Gao, Qingqing; Li, Baizhou; Sun, Chongran; Wang, Qiyuan; Chen, Qin; Sun, Bing; Shen, Hong; Zhu, Keqing; Zhang, Jianmin; Liu, Chong

2017-10-01

The availability of a comprehensive tissue library is essential for elucidating the function and pathology of human brains. Considering the irreplaceable status of the formalin-fixation-paraffin-embedding (FFPE) preparation in routine pathology and the advantage of ultra-low temperature to preserve nucleic acids and proteins for multi-omics studies, these methods have become major modalities for the construction of brain tissue libraries. Nevertheless, the use of FFPE and snap-frozen samples is limited in high-resolution histological analyses because the preparation destroys tissue integrity and/or many important cellular markers. To overcome these limitations, we detailed a protocol to prepare and analyze frozen human brain samples that is particularly suitable for high-resolution multiplex immunohistological studies. As an alternative, we offered an optimized procedure to rescue snap-frozen tissues for the same purpose. Importantly, we provided a guideline to construct libraries of frozen tissue with minimal effort, cost and space. Taking advantage of this new tissue preparation modality to nicely preserve the cellular information that was otherwise damaged using conventional methods and to effectively remove tissue autofluorescence, we described the high-resolution landscape of the cellular composition in both lower-grade gliomas and glioblastoma multiforme samples. Our work showcases the great value of fixed frozen tissue in understanding the cellular mechanisms of CNS functions and abnormalities.

Neurosurgery contact handheld probe based on sapphire shaped crystal

NASA Astrophysics Data System (ADS)

Shikunova, I. A.; Stryukov, D. O.; Rossolenko, S. N.; Kiselev, A. M.; Kurlov, V. N.

2017-01-01

A handheld contact probe based on sapphire shaped crystal is developed for intraoperative spectrally-resolved optical diagnostics, laser coagulation and aspiration of malignant brain tissue. The technology was integrated into the neurosurgical workflow for intraoperative real-time identification and removing of invasive brain cancer.

Mesh electronics: a new paradigm for tissue-like brain probes.

PubMed

Hong, Guosong; Yang, Xiao; Zhou, Tao; Lieber, Charles M

2018-06-01

Existing implantable neurotechnologies for understanding the brain and treating neurological diseases have intrinsic properties that have limited their capability to achieve chronically-stable brain interfaces with single-neuron spatiotemporal resolution. These limitations reflect what has been dichotomy between the structure and mechanical properties of living brain tissue and non-living neural probes. To bridge the gap between neural and electronic networks, we have introduced the new concept of mesh electronics probes designed with structural and mechanical properties such that the implant begins to 'look and behave' like neural tissue. Syringe-implanted mesh electronics have led to the realization of probes that are neuro-attractive and free of the chronic immune response, as well as capable of stable long-term mapping and modulation of brain activity at the single-neuron level. This review provides a historical overview of a 10-year development of mesh electronics by highlighting the tissue-like design, syringe-assisted delivery, seamless neural tissue integration, and single-neuron level chronic recording stability of mesh electronics. We also offer insights on unique near-term opportunities and future directions for neuroscience and neurology that now are available or expected for mesh electronics neurotechnologies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

An Australian Brain Bank: a critical investment with a high return!

PubMed

Sheedy, D; Garrick, T; Dedova, I; Hunt, C; Miller, R; Sundqvist, N; Harper, C

2008-09-01

Research into neuropsychiatric disorders, including alcohol-related problems, is limited in part by the lack of appropriate animal models. However, the development of new technologies in pathology and molecular biology means that many more questions can be addressed using appropriately stored human brain tissues. The New South Wales Tissue Resource Centre (TRC) in the University of Sydney (Australia) is a human brain bank that can provide tissues to the neuroscience research community studying alcohol-related brain disorders, schizophrenia, depression and bipolar disorders. Carefully standardised operational protocols and integrated information systems means that the TRC can provide high quality, accurately characterised, tissues for research. A recent initiative, the pre-mortem donor program called "Using our Brains", encourages individuals without neuropsychiatric illness to register as control donors, a critical group for all research. Community support for this program is strong with over 2,000 people registering their interest. Discussed herein are the protocols pertaining to this multifaceted facility and the benefits of investment, both scientific and financial, to neuroscience researchers and the community at large.

Quantitative measurement of intact alpha-synuclein proteoforms from post-mortem control and Parkinson's disease brain tissue by intact protein mass spectrometry.

PubMed

Kellie, John F; Higgs, Richard E; Ryder, John W; Major, Anthony; Beach, Thomas G; Adler, Charles H; Merchant, Kalpana; Knierman, Michael D

2014-07-23

A robust top down proteomics method is presented for profiling alpha-synuclein species from autopsied human frontal cortex brain tissue from Parkinson's cases and controls. The method was used to test the hypothesis that pathology associated brain tissue will have a different profile of post-translationally modified alpha-synuclein than the control samples. Validation of the sample processing steps, mass spectrometry based measurements, and data processing steps were performed. The intact protein quantitation method features extraction and integration of m/z data from each charge state of a detected alpha-synuclein species and fitting of the data to a simple linear model which accounts for concentration and charge state variability. The quantitation method was validated with serial dilutions of intact protein standards. Using the method on the human brain samples, several previously unreported modifications in alpha-synuclein were identified. Low levels of phosphorylated alpha synuclein were detected in brain tissue fractions enriched for Lewy body pathology and were marginally significant between PD cases and controls (p = 0.03).

Neocortical Transplants in the Mammalian Brain Lack a Blood-Brain Barrier to Macromolecules

NASA Astrophysics Data System (ADS)

Rosenstein, Jeffrey M.

1987-02-01

In order to determine whether the blood-brain barrier was present in transplants of central nervous tissue, fetal neocortex, which already possesses blood-brain and blood-cerebrospinal fluid barriers to protein, was grafted into the undamaged fourth ventricle or directly into the neocortex of recipient rats. Horseradish peroxidase or a conjugated human immunoglobulin G-peroxidase molecule was systemically administered into the host. These proteins were detected within the cortical transplants within 2 minutes regardless of the age of the donor or postoperative time. At later times these compounds, which normally do not cross the blood-brain barrier, inundated the grafts and adjacent host brain and also entered the cerebrospinal fluid. Endogenous serum albumin detected immunocytochemically in untreated hosts had a comparable although less extensive distribution. Thus, transplants of fetal central nervous tissue have permanent barrier dysfunction, probably due to microvascular changes, and are not integrated physiologically within the host. Blood-borne compounds, either systemically administered or naturally occurring, which should never contact normal brain tissue, have direct access to these transplants and might affect neuronal function.

Tissue-like Neural Probes for Understanding and Modulating the Brain.

PubMed

Hong, Guosong; Viveros, Robert D; Zwang, Theodore J; Yang, Xiao; Lieber, Charles M

2018-03-19

Electrophysiology tools have contributed substantially to understanding brain function, yet the capabilities of conventional electrophysiology probes have remained limited in key ways because of large structural and mechanical mismatches with respect to neural tissue. In this Perspective, we discuss how the general goal of probe design in biochemistry, that the probe or label have a minimal impact on the properties and function of the system being studied, can be realized by minimizing structural, mechanical, and topological differences between neural probes and brain tissue, thus leading to a new paradigm of tissue-like mesh electronics. The unique properties and capabilities of the tissue-like mesh electronics as well as future opportunities are summarized. First, we discuss the design of an ultraflexible and open mesh structure of electronics that is tissue-like and can be delivered in the brain via minimally invasive syringe injection like molecular and macromolecular pharmaceuticals. Second, we describe the unprecedented tissue healing without chronic immune response that leads to seamless three-dimensional integration with a natural distribution of neurons and other key cells through these tissue-like probes. These unique characteristics lead to unmatched stable long-term, multiplexed mapping and modulation of neural circuits at the single-neuron level on a year time scale. Last, we offer insights on several exciting future directions for the tissue-like electronics paradigm that capitalize on their unique properties to explore biochemical interactions and signaling in a "natural" brain environment.

Development of an experimental model of brain tissue heterotopia in the lung

PubMed Central

Quemelo, Paulo Roberto Veiga; Sbragia, Lourenço; Peres, Luiz Cesar

2007-01-01

Summary The presence of heterotopic brain tissue in the lung is a rare abnormality. The cases reported thus far are usually associated with neural tube defects (NTD). As there are no reports of experimental models of NTD that present this abnormality, the objective of the present study was to develop a surgical method of brain tissue heterotopia in the lung. We used 24 pregnant Swiss mice divided into two groups of 12 animals each, denoted 17GD and 18GD according to the gestational day (GD) when caesarean section was performed to collect the fetuses. Surgery was performed on the 15th GD, one fetus was removed by hysterectomy and its brain tissue was cut into small fragments and implanted in the lung of its litter mates. Thirty-four live fetuses were obtained from the 17GD group. Of these, eight (23.5%) were used as control (C), eight (23.5%) were sham operated (S) and 18 (52.9%) were used for pulmonary brain tissue implantation (PBI). Thirty live fetuses were obtained from the females of the 18GD group. Of these, eight (26.6%) were C, eight (26.6%) S and 14 (46.6%) were used for PBI. Histological examination of the fetal trunks showed implantation of GFAP-positive brain tissue in 85% of the fetuses of the 17GD group and in 100% of those of the 18GD group, with no significant difference between groups for any of the parameters analysed. The experimental model proved to be efficient and of relatively simple execution, showing complete integration of the brain tissue with pulmonary and pleural tissue and thus representing a model that will permit the study of different aspects of cell implantation and interaction. PMID:17877535

Autism Post-Mortem Neuroinformatic Resource: The Autism Tissue Program (ATP) Informatics Portal

ERIC Educational Resources Information Center

Brimacombe, Michael B.; Pickett, Richard; Pickett, Jane

2007-01-01

The Autism Tissue Program (ATP) was established to oversee and manage brain donations related to neurological research in autism. The ATP Informatics Portal (www.atpportal.org) is an integrated data access system based on Oracle technology, developed to provide access for researchers to information on this rare tissue resource. It also permits…

LINKS: learning-based multi-source IntegratioN frameworK for Segmentation of infant brain images.

PubMed

Wang, Li; Gao, Yaozong; Shi, Feng; Li, Gang; Gilmore, John H; Lin, Weili; Shen, Dinggang

2015-03-01

Segmentation of infant brain MR images is challenging due to insufficient image quality, severe partial volume effect, and ongoing maturation and myelination processes. In the first year of life, the image contrast between white and gray matters of the infant brain undergoes dramatic changes. In particular, the image contrast is inverted around 6-8months of age, and the white and gray matter tissues are isointense in both T1- and T2-weighted MR images and thus exhibit the extremely low tissue contrast, which poses significant challenges for automated segmentation. Most previous studies used multi-atlas label fusion strategy, which has the limitation of equally treating the different available image modalities and is often computationally expensive. To cope with these limitations, in this paper, we propose a novel learning-based multi-source integration framework for segmentation of infant brain images. Specifically, we employ the random forest technique to effectively integrate features from multi-source images together for tissue segmentation. Here, the multi-source images include initially only the multi-modality (T1, T2 and FA) images and later also the iteratively estimated and refined tissue probability maps of gray matter, white matter, and cerebrospinal fluid. Experimental results on 119 infants show that the proposed method achieves better performance than other state-of-the-art automated segmentation methods. Further validation was performed on the MICCAI grand challenge and the proposed method was ranked top among all competing methods. Moreover, to alleviate the possible anatomical errors, our method can also be combined with an anatomically-constrained multi-atlas labeling approach for further improving the segmentation accuracy. Copyright © 2014 Elsevier Inc. All rights reserved.

LINKS: Learning-based multi-source IntegratioN frameworK for Segmentation of infant brain images

PubMed Central

Wang, Li; Gao, Yaozong; Shi, Feng; Li, Gang; Gilmore, John H.; Lin, Weili; Shen, Dinggang

2014-01-01

Segmentation of infant brain MR images is challenging due to insufficient image quality, severe partial volume effect, and ongoing maturation and myelination processes. In the first year of life, the image contrast between white and gray matters of the infant brain undergoes dramatic changes. In particular, the image contrast is inverted around 6-8 months of age, and the white and gray matter tissues are isointense in both T1- and T2-weighted MR images and thus exhibit the extremely low tissue contrast, which poses significant challenges for automated segmentation. Most previous studies used multi-atlas label fusion strategy, which has the limitation of equally treating the different available image modalities and is often computationally expensive. To cope with these limitations, in this paper, we propose a novel learning-based multi-source integration framework for segmentation of infant brain images. Specifically, we employ the random forest technique to effectively integrate features from multi-source images together for tissue segmentation. Here, the multi-source images include initially only the multi-modality (T1, T2 and FA) images and later also the iteratively estimated and refined tissue probability maps of gray matter, white matter, and cerebrospinal fluid. Experimental results on 119 infants show that the proposed method achieves better performance than other state-of-the-art automated segmentation methods. Further validation was performed on the MICCAI grand challenge and the proposed method was ranked top among all competing methods. Moreover, to alleviate the possible anatomical errors, our method can also be combined with an anatomically-constrained multi-atlas labeling approach for further improving the segmentation accuracy. PMID:25541188

[Effect of ginsenoside Rb1 on cerebral infarction volume and IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion injury model rats].

PubMed

Liu, Jun-Wei; Ren, Ye-Long; Liu, Xu-Ling; Xia, Hong-Lian; Zhang, Hui-Ling; Jin, Shen-Hui; Dai, Qin-Xue; Wang, Jun-Lu

2013-12-01

To investigate the effect of ginsenoside Rb1 on cerebral infarction volume as well as IL-1 beta in the brain tissue and sera of focal cerebral ischemia/reperfusion (I/R) injury model rats. The I/R rat model was established by using thread according to Zea-Longa. SD rats were randomly divided into five groups, i.e., the sham-operation group, the model group, the low dose ginsenoside Rb1 (20 mg/kg) group, the medium dose ginsenoside Rb1 group (40 mg/kg), and the high dose ginsenoside Rb1 group (80 mg/kg), 12 in each group. Rats in the sham-operation group only received middle cerebral artery occlusion (MCAO) but without thread insertion. The MCAO model was prepared in the rest 4 groups, followed by MCAO2 h later. Ginsenoside Rb1 at each dose was peritoneally administrated to rats in corresponding groups immediately after cerebral ischemia. Equal volume of normal saline was administered to rats in the sham-operation group. Rats' cerebral infarction volume, integrals of neurologic defect degree, expression of IL-1 beta content in the brain tissue and sera were observed 24 h after 2-h cerebral I/R. In the model group, integrals of neurologic defect degree were improved (P < 0.01), IL-1 beta positive cells in the brain tissue increased and serum IL-1 beta content elevated (P < 0.05), when compared with the sham-operation group. In comparison of the model group, integrals of neurologic defect degree were lowered in the medium dose and high dose ginsenoside Rb1 groups (P < 0.05, P < 0.01). The cerebral infarction volume was all shrunken in each ginsenoside Rb1 group, IL-1 beta positive cells in the brain tissue decreased, and IL-1 beta content in serum reduced (P < 0.01, P < 0.05). Compared with the low dose ginsenoside Rb1 group, integrals of neurologic defect degree decreased, the cerebral infarction volume shrunken, and IL-1 beta content in serum reduced in the high dose ginsenoside Rb1 group (P < 0.01, P < 0.05). Ginsenoside Rb1 (20, 40, 80 mg/kg) might effectively release local cerebral ischemia by down-regulating the IL-1 beta expression.

Delta-aminolevulinic acid dehydratase enzyme activity in blood, brain, and liver of lead-dosed ducks

USGS Publications Warehouse

Dieter, M.P.; Finley, M.T.

1979-01-01

Mallard ducks were dosed with a single shotgun pellet (ca. 200 mg lead). After 1 month there was about 1 ppm lead in blood, 2.5 in liver, and 0.5 in brain. Lead-induced inhibition of delta-aminolevulinic acid dehydratase enzyme in blood and cerebellum was much greater than in cerebral hemisphere or liver and was strongly correlated with the lead concentration in these tissues. The cerebellar portion of the brain was more sensitive to delta-aminolevulinic acid dehydratase enzyme inhibition by lead than were the other tissues examined. There was also a greater increase in the glial cell marker enzyme, butyrylcholinesterase, in cerebellum than in cerebral hemisphere, suggesting that nonregenerating neuronal cells were destroyed by lead and replaced by glial cells in that portion of the brain. Even partial loss of cerebellar tissue is severely debilitating in waterfowl, because functions critical to survival such as visual, auditory, motor, and reflex responses are integrated at this brain center.

Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes

NASA Astrophysics Data System (ADS)

Xie, Chong; Liu, Jia; Fu, Tian-Ming; Dai, Xiaochuan; Zhou, Wei; Lieber, Charles M.

2015-12-01

Direct electrical recording and stimulation of neural activity using micro-fabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the dimensional and mechanical mismatch of these probes with the brain tissue limits their stability in chronic implants and decreases the neuron-device contact. Here, we demonstrate the realization of a three-dimensional macroporous nanoelectronic brain probe that combines ultra-flexibility and subcellular feature sizes to overcome these limitations. Built-in strains controlling the local geometry of the macroporous devices are designed to optimize the neuron/probe interface and to promote integration with the brain tissue while introducing minimal mechanical perturbation. The ultra-flexible probes were implanted frozen into rodent brains and used to record multiplexed local field potentials and single-unit action potentials from the somatosensory cortex. Significantly, histology analysis revealed filling-in of neural tissue through the macroporous network and attractive neuron-probe interactions, consistent with long-term biocompatibility of the device.

The NSW brain tissue resource centre: Banking for alcohol and major neuropsychiatric disorders research.

PubMed

Sutherland, G T; Sheedy, D; Stevens, J; McCrossin, T; Smith, C C; van Roijen, M; Kril, J J

2016-05-01

The New South Wales Brain Tissue Resource Centre (NSWBTRC) at the University of Sydney (Australia) is an established human brain bank providing tissue to the neuroscience research community for investigations on alcohol-related brain damage and major psychiatric illnesses such as schizophrenia. The NSWBTRC relies on wide community engagement to encourage those with and without neuropsychiatric illness to consent to donation through its allied research programs. The subsequent provision of high-quality samples relies on standardized operational protocols, associated clinical data, quality control measures, integrated information systems, robust infrastructure, and governance. These processes are continually augmented to complement the changes in internal and external governance as well as the complexity and diversity of advanced investigation techniques. This report provides an overview of the dynamic process of brain banking and discusses the challenges of meeting the future needs of researchers, including synchronicity with other disease-focus collections. Copyright © 2016 Elsevier Inc. All rights reserved.

Fully integrated reflection-mode photoacoustic, two-photon, and second harmonic generation microscopy in vivo

NASA Astrophysics Data System (ADS)

Song, Wei; Xu, Qiang; Zhang, Yang; Zhan, Yang; Zheng, Wei; Song, Liang

2016-08-01

The ability to obtain comprehensive structural and functional information from intact biological tissue in vivo is highly desirable for many important biomedical applications, including cancer and brain studies. Here, we developed a fully integrated multimodal microscopy that can provide photoacoustic (optical absorption), two-photon (fluorescence), and second harmonic generation (SHG) information from tissue in vivo, with intrinsically co-registered images. Moreover, using a delicately designed optical-acoustic coupling configuration, a high-frequency miniature ultrasonic transducer was integrated into a water-immersion optical objective, thus allowing all three imaging modalities to provide a high lateral resolution of ~290 nm with reflection-mode imaging capability, which is essential for studying intricate anatomy, such as that of the brain. Taking advantage of the complementary and comprehensive contrasts of the system, we demonstrated high-resolution imaging of various tissues in living mice, including microvasculature (by photoacoustics), epidermis cells, cortical neurons (by two-photon fluorescence), and extracellular collagen fibers (by SHG). The intrinsic image co-registration of the three modalities conveniently provided improved visualization and understanding of the tissue microarchitecture. The reported results suggest that, by revealing complementary tissue microstructures in vivo, this multimodal microscopy can potentially facilitate a broad range of biomedical studies, such as imaging of the tumor microenvironment and neurovascular coupling.

Apparent diffusion coefficient of the normal human brain for various experimental conditions

NASA Astrophysics Data System (ADS)

Moraru, Luminita; Dimitrievici, Lucian

2017-01-01

Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) is being increasingly used to assess both brain tissues and cerebrospinal fluid integrity. In this paper we study inter-site reproducibility of the apparent diffusion coefficient values for the main cerebral tissues such as gray matter, white matter and into cerebrospinal fluid and for three different stacks of slices that were spaced at L = 79.8, 84.9 and 90 mm. We assessed the impact of the attenuation factor and diffusion gradient on the results reproducibility.

Patient-tailored multimodal neuroimaging, visualization and quantification of human intra-cerebral hemorrhage

NASA Astrophysics Data System (ADS)

Goh, Sheng-Yang M.; Irimia, Andrei; Vespa, Paul M.; Van Horn, John D.

2016-03-01

In traumatic brain injury (TBI) and intracerebral hemorrhage (ICH), the heterogeneity of lesion sizes and types necessitates a variety of imaging modalities to acquire a comprehensive perspective on injury extent. Although it is advantageous to combine imaging modalities and to leverage their complementary benefits, there are difficulties in integrating information across imaging types. Thus, it is important that efforts be dedicated to the creation and sustained refinement of resources for multimodal data integration. Here, we propose a novel approach to the integration of neuroimaging data acquired from human patients with TBI/ICH using various modalities; we also demonstrate the integrated use of multimodal magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) data for TBI analysis based on both visual observations and quantitative metrics. 3D models of healthy-appearing tissues and TBIrelated pathology are generated, both of which are derived from multimodal imaging data. MRI volumes acquired using FLAIR, SWI, and T2 GRE are used to segment pathology. Healthy tissues are segmented using user-supervised tools, and results are visualized using a novel graphical approach called a `connectogram', where brain connectivity information is depicted within a circle of radially aligned elements. Inter-region connectivity and its strength are represented by links of variable opacities drawn between regions, where opacity reflects the percentage longitudinal change in brain connectivity density. Our method for integrating, analyzing and visualizing structural brain changes due to TBI and ICH can promote knowledge extraction and enhance the understanding of mechanisms underlying recovery.

In situ characterization of the brain-microdevice interface using Device Capture Histology

PubMed Central

Woolley, Andrew J.; Desai, Himanshi A.; Steckbeck, Mitchell A.; Patel, Neil K.; Otto, Kevin J.

2011-01-01

Accurate assessment of brain-implantable microdevice bio-integration remains a formidable challenge. Prevailing histological methods require device extraction prior to tissue processing, often disrupting and removing the tissue of interest which had been surrounding the device. The Device-Capture Histology method, presented here, overcomes many limitations of the conventional Device-Explant Histology method, by collecting the device and surrounding tissue intact for subsequent labeling. With the implant remaining in situ, accurate and precise imaging of the morphologically preserved tissue at the brain/microdevice interface can then be collected and quantified. First, this article presents the Device-Capture Histology method for obtaining and processing the intact, undisturbed microdevice-tissue interface, and images using fluorescent labeling and confocal microscopy. Second, this article gives examples of how to quantify features found in the captured peridevice tissue. We also share histological data capturing 1) the impact of microdevice implantation on tissue, 2) the effects of an experimental anti-inflammatory coating, 3) a dense grouping of cell nuclei encapsulating a long-term implant, and 4) atypical oligodendrocyte organization neighboring a longterm implant. Data sets collected using the Device-Capture Histology method are presented to demonstrate the significant advantages of processing the intact microdevice-tissue interface, and to underscore the utility of the method in understanding the effects of the brain-implantable microdevices on nearby tissue. PMID:21802446

Piezosurgery prevents brain tissue damage: an experimental study on a new rat model.

PubMed

Pavlíková, G; Foltán, R; Burian, M; Horká, E; Adámek, S; Hejčl, A; Hanzelka, T; Sedý, J

2011-08-01

Piezosurgery is a promising meticulous system for bone cutting, based on ultrasound microvibrations. It is thought that the impact of piezosurgery on the integrity of soft tissue is generally low, but it has not been examined critically. The authors undertook an experimental study to evaluate the brain tissue response to skull bone removal using piezosurgery compared with a conventional drilling method. In Wistar male rats, a circular bone window was drilled to the parietal bone using piezosurgery on one side and a conventional bone drill on the other side. The behavioural performance of animals was evaluated using the motor BBB test and sensory plantar test. The brains of animals were evaluated by magnetic resonance imaging (MRI) and histology. The results of MRI showed significantly increased depth and width of the brain lesion in the region of conventional drilling compared with the region where piezosurgery was used. Cresylviolet and NF 160 staining confirmed these findings. There was no significant difference in any of the behavioural tests between the two groups. In conclusion, piezosurgery is a safe method for the performance of osteotomy in close relation to soft tissue, including an extremely injury-sensitive tissue such as brain. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Numerical analysis of the diffusive mass transport in brain tissues with applications to optical sensors

NASA Astrophysics Data System (ADS)

Neculae, Adrian P.; Otte, Andreas; Curticapean, Dan

2013-03-01

In the brain-cell microenvironment, diffusion plays an important role: apart from delivering glucose and oxygen from the vascular system to brain cells, it also moves informational substances between cells. The brain is an extremely complex structure of interwoven, intercommunicating cells, but recent theoretical and experimental works showed that the classical laws of diffusion, cast in the framework of porous media theory, can deliver an accurate quantitative description of the way molecules are transported through this tissue. The mathematical modeling and the numerical simulations are successfully applied in the investigation of diffusion processes in tissues, replacing the costly laboratory investigations. Nevertheless, modeling must rely on highly accurate information regarding the main parameters (tortuosity, volume fraction) which characterize the tissue, obtained by structural and functional imaging. The usual techniques to measure the diffusion mechanism in brain tissue are the radiotracer method, the real time iontophoretic method and integrative optical imaging using fluorescence microscopy. A promising technique for obtaining the values for characteristic parameters of the transport equation is the direct optical investigation using optical fibers. The analysis of these parameters also reveals how the local geometry of the brain changes with time or under pathological conditions. This paper presents a set of computations concerning the mass transport inside the brain tissue, for different types of cells. By measuring the time evolution of the concentration profile of an injected substance and using suitable fitting procedures, the main parameters characterizing the tissue can be determined. This type of analysis could be an important tool in understanding the functional mechanisms of effective drug delivery in complex structures such as the brain tissue. It also offers possibilities to realize optical imaging methods for in vitro and in vivo measurements using optical fibers. The model also may help in radiotracer biomarker models for the understanding of the mechanism of action of new chemical entities.

SU-E-T-326: Dosimetric Impact of Beam Energies and Jaw Tracking On Intracranial Tumors Using RapidArc

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Keeling, V; Ali, I

2015-06-15

Purpose: To determine the dosimetric impact of jaw tracking and beam energies on dose conformity and normal-brain-tissue doses for intracranial tumors using VMAT (RapidArc). Methods: Seven patients with 1–2 and three patients with 4–6 intracranial tumors were planned using RapidArc for Varian TrueBeam STx machine with beam energies 6MV-FFF (Flattening-Filter-Free), 8MV, 10MV, and 10MV-FFF. The prescription dose ranged from 14–23Gy. Between 2 and 8 arcs were used with the following geometries: 2 full coplanar arcs and the non-coplanar half arcs. Plans were optimized (jaw tracking ON) with a high priority to Normal-Tissue-Objective and normal-brain-tissue. Plans were calculated on 1mm gridmore » size using AAA algorithm and then normalized so that 99% of each target volume received the prescription dose. Plans for the 6MV-FFF were also optimized without jaw tracking (No-JT) for comparison. Plan quality was assessed by target coverage using Paddick Conformity Index (PCI), sparing of normal-brain-tissue through analysis of V4Gy, V8Gy and V12Gy, and integral dose. Results: The average PCI ± standard deviation was 0.76±0.21 and 0.76±0.22 for 6MV-FFF and 10 MV-FFF, respectively. The average ratio in normal brain tissue volume (reported as follows V4,V8,V12) were (1.12±0.07,1.12±0.07,1.14±0.04), (1.12±0.08,1.12±0.09,1.13±0.06), (1.19±0.10,1.18±0.10,1.20±0.04), and (1.04±0.03,1.03±0.03,1.03±0.04) for 8MV/6MV-FFF, 10MV-FFF/6MV-FFF, 10MV/6MV-FFF, 6MV-FFF No-JT/6MV-FFF, respectively. Statistically significant differences in normal-brain-tissue for V4, V8, and V12 were observed in all cases for the different energies (p-values <0.05). V4 data shows significant differences in JT vs. No-JT (p=0.04), however no difference was found for V8 and V12. Brain tissue sparing from best to worst occurred in this order 6MV-FFF, 6MV-FFF no-JT, 10MV-FFF, 8MV, and 10MV. The average ratio of integral brain dose was 1.05±0.04 (p=0.21), 1.04±0.05 (p=0.33), 1.09±0.06 (p=0.04), and 1.02±0.06 (p=0.61) for 8MV/6MV-FFF, 10MV-FFF/6MV-FFF, 10MV/6MV-FFF, and 6MV-FFF No-JT/6MV-FFF, respectively. Conclusion: Normal brain tissue and integral dose improved using the lower energy and FFF beams, though plan conformity showed energy independence.« less

Clinical applications of image guided-intensity modulated radiation therapy (IG-IMRT) for conformal avoidance of normal tissue

NASA Astrophysics Data System (ADS)

Gutierrez, Alonso Navar

2007-12-01

Recent improvements in imaging technology and radiation delivery have led to the development of advanced treatment techniques in radiotherapy which have opened the door for novel therapeutic approaches to improve the efficacy of radiation cancer treatments. Among these advances is image-guided, intensity modulated radiation therapy (IG-IMRT), in which imaging is incorporated to aid in inter-/intra-fractional target localization and to ensure accurate delivery of precise and highly conformal dose distributions. In principle, clinical implementation of IG-IMRT should improve normal tissue sparing and permit effective biological dose escalation thus widening the radiation therapeutic window and lead to increases in survival through improved local control of primary neoplastic diseases. Details of the development of three clinical applications made possible solely with IG-IMRT radiation delivery techniques are presented: (1) Laparoscopically implanted tissue expander radiotherapy (LITE-RT) has been developed to enhance conformal avoidance of normal tissue during the treatment of intra-abdominopelvic cancers. LITE-RT functions by geometrically displacing surrounding normal tissue and isolating the target volume through the interfractional inflation of a custom-shaped tissue expander throughout the course of treatment. (2) The unique delivery geometry of helical tomotherapy, a novel form of IG-IMRT, enables the delivery of composite treatment plan m which whole brain radiotherapy (WBRT) with hippocampal avoidance, hypothesized to reduce the risk of memory function decline and improve the patient's quality of life, and simultaneously integrated boost to multiple brain metastases to improve intracranial tumor control is achieved. (3) Escalation of biological dose to targets through integrated, selective subvolume boosts have been shown to efficiently increase tumor dose without significantly increasing normal tissue dose. Helical tomotherapy was used to investigate the feasibility of delivering a simultaneously integrated subvolume boost to canine nasal tumors and was found to dramatically increase estimated 1-year tumor control probability (TCP) without increasing the dose to the eyes, so as to preserve vision, and to the brain, so as to prevent neuropathy.

Light-scattering signal may indicate critical time zone to rescue brain tissue after hypoxia

NASA Astrophysics Data System (ADS)

Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

2011-02-01

A light-scattering signal, which is sensitive to cellular/subcellular structural integrity, is a potential indicator of brain tissue viability because metabolic energy is used in part to maintain the structure of cells. We previously observed a unique triphasic scattering change (TSC) at a certain time after oxygen/glucose deprivation for blood-free rat brains; TSC almost coincided with the cerebral adenosine triphosphate (ATP) depletion. We examine whether such TSC can be observed in the presence of blood in vivo, for which transcranial diffuse reflectance measurement is performed for rat brains during hypoxia induced by nitrogen gas inhalation. At a certain time after hypoxia, diffuse reflectance intensity in the near-infrared region changes in three phases, which is shown by spectroscopic analysis to be due to scattering change in the tissue. During hypoxia, rats are reoxygenated at various time points. When the oxygen supply is started before TSC, all rats survive, whereas no rats survive when the oxygen supply is started after TSC. Survival is probabilistic when the oxygen supply is started during TSC, indicating that the period of TSC can be regarded as a critical time zone for rescuing the brain. The results demonstrate that light scattering signal can be an indicator of brain tissue reversibility.

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain

PubMed Central

Zhou, Tao; Hong, Guosong; Fu, Tian-Ming; Yang, Xiao; Schuhmann, Thomas G.; Viveros, Robert D.; Lieber, Charles M.

2017-01-01

Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes. Confocal fluorescence microscopy images of the perpendicular and parallel brain slices containing mesh electronics showed that the distribution of astrocytes, microglia, and neurons became uniform from 2–12 wk, whereas flexible thin-film probes yield a marked accumulation of astrocytes and microglia and decrease of neurons for the same period. Quantitative analyses of 4- and 12-wk data showed that the signals for neurons, axons, astrocytes, and microglia are nearly the same from the mesh electronics surface to the baseline far from the probes, in contrast to flexible polymer probes, which show decreases in neuron and increases in astrocyte and microglia signals. Notably, images of sagittal brain slices containing nearly the entire mesh electronics probe showed that the tissue interface was uniform and neurons and neurofilaments penetrated through the mesh by 3 mo postimplantation. The minimal immune response and seamless interface with brain tissue postimplantation achieved by ultraflexible open mesh electronics probes provide substantial advantages and could enable a wide range of opportunities for in vivo chronic recording and modulation of brain activity in the future. PMID:28533392

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain.

PubMed

Zhou, Tao; Hong, Guosong; Fu, Tian-Ming; Yang, Xiao; Schuhmann, Thomas G; Viveros, Robert D; Lieber, Charles M

2017-06-06

Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes. Confocal fluorescence microscopy images of the perpendicular and parallel brain slices containing mesh electronics showed that the distribution of astrocytes, microglia, and neurons became uniform from 2-12 wk, whereas flexible thin-film probes yield a marked accumulation of astrocytes and microglia and decrease of neurons for the same period. Quantitative analyses of 4- and 12-wk data showed that the signals for neurons, axons, astrocytes, and microglia are nearly the same from the mesh electronics surface to the baseline far from the probes, in contrast to flexible polymer probes, which show decreases in neuron and increases in astrocyte and microglia signals. Notably, images of sagittal brain slices containing nearly the entire mesh electronics probe showed that the tissue interface was uniform and neurons and neurofilaments penetrated through the mesh by 3 mo postimplantation. The minimal immune response and seamless interface with brain tissue postimplantation achieved by ultraflexible open mesh electronics probes provide substantial advantages and could enable a wide range of opportunities for in vivo chronic recording and modulation of brain activity in the future.

Microsurgery Simulator of Cerebral Aneurysm Clipping with Interactive Cerebral Deformation Featuring a Virtual Arachnoid.

PubMed

Shono, Naoyuki; Kin, Taichi; Nomura, Seiji; Miyawaki, Satoru; Saito, Toki; Imai, Hideaki; Nakatomi, Hirofumi; Oyama, Hiroshi; Saito, Nobuhito

2018-05-01

A virtual reality simulator for aneurysmal clipping surgery is an attractive research target for neurosurgeons. Brain deformation is one of the most important functionalities necessary for an accurate clipping simulator and is vastly affected by the status of the supporting tissue, such as the arachnoid membrane. However, no virtual reality simulator implementing the supporting tissue of the brain has yet been developed. To develop a virtual reality clipping simulator possessing interactive brain deforming capability closely dependent on arachnoid dissection and apply it to clinical cases. Three-dimensional computer graphics models of cerebral tissue and surrounding structures were extracted from medical images. We developed a new method for modifiable cerebral tissue complex deformation by incorporating a nonmedical image-derived virtual arachnoid/trabecula in a process called multitissue integrated interactive deformation (MTIID). MTIID made it possible for cerebral tissue complexes to selectively deform at the site of dissection. Simulations for 8 cases of actual clipping surgery were performed before surgery and evaluated for their usefulness in surgical approach planning. Preoperatively, each operative field was precisely reproduced and visualized with the virtual brain retraction defined by users. The clear visualization of the optimal approach to treating the aneurysm via an appropriate arachnoid incision was possible with MTIID. A virtual clipping simulator mainly focusing on supporting tissues and less on physical properties seemed to be useful in the surgical simulation of cerebral aneurysm clipping. To our knowledge, this article is the first to report brain deformation based on supporting tissues.

An Australian Brain Bank: a critical investment with a high return!

PubMed Central

Garrick, T.; Dedova, I.; Hunt, C.; Miller, R.; Sundqvist, N.; Harper, C.

2012-01-01

Research into neuropsychiatric disorders, including alcohol-related problems, is limited in part by the lack of appropriate animal models. However, the development of new technologies in pathology and molecular biology means that many more questions can be addressed using appropriately stored human brain tissues. The New South Wales Tissue Resource Centre (TRC) in the University of Sydney (Australia) is a human brain bank that can provide tissues to the neuroscience research community studying alcohol-related brain disorders, schizophrenia, depression and bipolar disorders. Carefully standardised operational protocols and integrated information systems means that the TRC can provide high quality, accurately characterised, tissues for research. A recent initiative, the pre-mortem donor program called “Using our Brains”, encourages individuals without neuropsychiatric illness to register as control donors, a critical group for all research. Community support for this program is strong with over 2,000 people registering their interest. Discussed herein are the protocols pertaining to this multifaceted facility and the benefits of investment, both scientific and financial, to neuroscience researchers and the community at large. PMID:18543078

78 FR 6334 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-30

..., Oral and Skin Sciences Integrated Review Group, Musculoskeletal Tissue Engineering Study Section. [email protected] . Name of Committee: Brain Disorders and Clinical Neuroscience Integrated Review Group, Clinical Neuroscience and Neurodegeneration Study Section. Date: February 26, 2013. Time: 8:00 a.m. to 5:00...

Integration of Sparse Multi-modality Representation and Anatomical Constraint for Isointense Infant Brain MR Image Segmentation

PubMed Central

Wang, Li; Shi, Feng; Gao, Yaozong; Li, Gang; Gilmore, John H.; Lin, Weili; Shen, Dinggang

2014-01-01

Segmentation of infant brain MR images is challenging due to poor spatial resolution, severe partial volume effect, and the ongoing maturation and myelination process. During the first year of life, the brain image contrast between white and gray matters undergoes dramatic changes. In particular, the image contrast inverses around 6–8 months of age, where the white and gray matter tissues are isointense in T1 and T2 weighted images and hence exhibit the extremely low tissue contrast, posing significant challenges for automated segmentation. In this paper, we propose a general framework that adopts sparse representation to fuse the multi-modality image information and further incorporate the anatomical constraints for brain tissue segmentation. Specifically, we first derive an initial segmentation from a library of aligned images with ground-truth segmentations by using sparse representation in a patch-based fashion for the multi-modality T1, T2 and FA images. The segmentation result is further iteratively refined by integration of the anatomical constraint. The proposed method was evaluated on 22 infant brain MR images acquired at around 6 months of age by using a leave-one-out cross-validation, as well as other 10 unseen testing subjects. Our method achieved a high accuracy for the Dice ratios that measure the volume overlap between automated and manual segmentations, i.e., 0.889±0.008 for white matter and 0.870±0.006 for gray matter. PMID:24291615

Integration of Sparse Multi-modality Representation and Geometrical Constraint for Isointense Infant Brain Segmentation

PubMed Central

Wang, Li; Shi, Feng; Li, Gang; Lin, Weili; Gilmore, John H.; Shen, Dinggang

2014-01-01

Segmentation of infant brain MR images is challenging due to insufficient image quality, severe partial volume effect, and ongoing maturation and myelination process. During the first year of life, the signal contrast between white matter (WM) and gray matter (GM) in MR images undergoes inverse changes. In particular, the inversion of WM/GM signal contrast appears around 6–8 months of age, where brain tissues appear isointense and hence exhibit extremely low tissue contrast, posing significant challenges for automated segmentation. In this paper, we propose a novel segmentation method to address the above-mentioned challenge based on the sparse representation of the complementary tissue distribution information from T1, T2 and diffusion-weighted images. Specifically, we first derive an initial segmentation from a library of aligned multi-modality images with ground-truth segmentations by using sparse representation in a patch-based fashion. The segmentation is further refined by the integration of the geometrical constraint information. The proposed method was evaluated on 22 6-month-old training subjects using leave-one-out cross-validation, as well as 10 additional infant testing subjects, showing superior results in comparison to other state-of-the-art methods. PMID:24505729

Integration of sparse multi-modality representation and geometrical constraint for isointense infant brain segmentation.

PubMed

Wang, Li; Shi, Feng; Li, Gang; Lin, Weili; Gilmore, John H; Shen, Dinggang

2013-01-01

Segmentation of infant brain MR images is challenging due to insufficient image quality, severe partial volume effect, and ongoing maturation and myelination process. During the first year of life, the signal contrast between white matter (WM) and gray matter (GM) in MR images undergoes inverse changes. In particular, the inversion of WM/GM signal contrast appears around 6-8 months of age, where brain tissues appear isointense and hence exhibit extremely low tissue contrast, posing significant challenges for automated segmentation. In this paper, we propose a novel segmentation method to address the above-mentioned challenge based on the sparse representation of the complementary tissue distribution information from T1, T2 and diffusion-weighted images. Specifically, we first derive an initial segmentation from a library of aligned multi-modality images with ground-truth segmentations by using sparse representation in a patch-based fashion. The segmentation is further refined by the integration of the geometrical constraint information. The proposed method was evaluated on 22 6-month-old training subjects using leave-one-out cross-validation, as well as 10 additional infant testing subjects, showing superior results in comparison to other state-of-the-art methods.

Ultrasoft microwire neural electrodes improve chronic tissue integration.

PubMed

Du, Zhanhong Jeff; Kolarcik, Christi L; Kozai, Takashi D Y; Luebben, Silvia D; Sapp, Shawn A; Zheng, Xin Sally; Nabity, James A; Cui, X Tracy

2017-04-15

Chronically implanted neural multi-electrode arrays (MEA) are an essential technology for recording electrical signals from neurons and/or modulating neural activity through stimulation. However, current MEAs, regardless of the type, elicit an inflammatory response that ultimately leads to device failure. Traditionally, rigid materials like tungsten and silicon have been employed to interface with the relatively soft neural tissue. The large stiffness mismatch is thought to exacerbate the inflammatory response. In order to minimize the disparity between the device and the brain, we fabricated novel ultrasoft electrodes consisting of elastomers and conducting polymers with mechanical properties much more similar to those of brain tissue than previous neural implants. In this study, these ultrasoft microelectrodes were inserted and released using a stainless steel shuttle with polyethyleneglycol (PEG) glue. The implanted microwires showed functionality in acute neural stimulation. When implanted for 1 or 8weeks, the novel soft implants demonstrated significantly reduced inflammatory tissue response at week 8 compared to tungsten wires of similar dimension and surface chemistry. Furthermore, a higher degree of cell body distortion was found next to the tungsten implants compared to the polymer implants. Our results support the use of these novel ultrasoft electrodes for long term neural implants. One critical challenge to the translation of neural recording/stimulation electrode technology to clinically viable devices for brain computer interface (BCI) or deep brain stimulation (DBS) applications is the chronic degradation of device performance due to the inflammatory tissue reaction. While many hypothesize that soft and flexible devices elicit reduced inflammatory tissue responses, there has yet to be a rigorous comparison between soft and stiff implants. We have developed an ultra-soft microelectrode with Young's modulus lower than 1MPa, closely mimicking the brain tissue modulus. Here, we present a rigorous histological comparison of this novel ultrasoft electrode and conventional stiff electrode with the same size, shape and surface chemistry, implanted in rat brains for 1-week and 8-weeks. Significant improvement was observed for ultrasoft electrodes, including inflammatory tissue reaction, electrode-tissue integration as well as mechanical disturbance to nearby neurons. A full spectrum of new techniques were developed in this study, from insertion shuttle to in situ sectioning of the microelectrode to automated cell shape analysis, all of which should contribute new methods to the field. Finally, we showed the electrical functionality of the ultrasoft electrode, demonstrating the potential of flexible neural implant devices for future research and clinical use. Copyright © 2017. Published by Elsevier Ltd.

The adult brain tissue response to hollow fiber membranes of varying surface architecture with or without cotransplanted cells

NASA Astrophysics Data System (ADS)

Zhang, Ning

A variety of biomaterials have been chronically implanted into the central nervous system (CNS) for repair or therapeutic purposes. Regardless of the application, chronic implantation of materials into the CNS induces injury and elicits a wound healing response, eventually leading to the formation of a dense extracellular matrix (ECM)-rich scar tissue that is associated with the segregation of implanted materials from the surrounding normal tissue. Often this reaction results in impaired performance of indwelling CNS devices. In order to enhance the performance of biomaterial-based implantable devices in the CNS, this thesis investigated whether adult brain tissue response to implanted biomaterials could be manipulated by changing biomaterial surface properties or further by utilizing the biology of co-transplanted cells. Specifically, the adult rat brain tissue response to chronically implanted poly(acrylonitrile-vinylchloride) (PAN-PVC) hollow fiber membranes (HFMs) of varying surface architecture were examined temporally at 2, 4, and 12 weeks postimplantation. Significant differences were discovered in the brain tissue response to the PAN-PVC HFMs of varying surface architecture at 4 and 12 weeks. To extend this work, whether the soluble factors derived from a co-transplanted cellular component further affect the brain tissue response to an implanted HFM in a significant way was critically exploited. The cells used were astrocytes, whose ability to influence scar formation process following CNS injury by physical contact with the host tissue had been documented in the literature. Data indicated for the first time that astrocyte-derived soluble factors ameliorate the adult brain tissue reactivity toward HFM implants in an age-dependent manner. While immature astrocytes secreted soluble factors that suppressed the brain tissue reactivity around the implants, mature astrocytes secreted factors that enhanced the gliotic response. These findings prove the feasibility of ameliorating the CNS tissue reactivity toward biomaterials implants by varying biomaterial surface properties or incorporating scar-reductive factors derived from functional cells into implant constructs, therefore, provide guidance in the design of more integrative biomaterial-based implantable devices for CNS repair.

Rough Sets and Stomped Normal Distribution for Simultaneous Segmentation and Bias Field Correction in Brain MR Images.

PubMed

Banerjee, Abhirup; Maji, Pradipta

2015-12-01

The segmentation of brain MR images into different tissue classes is an important task for automatic image analysis technique, particularly due to the presence of intensity inhomogeneity artifact in MR images. In this regard, this paper presents a novel approach for simultaneous segmentation and bias field correction in brain MR images. It integrates judiciously the concept of rough sets and the merit of a novel probability distribution, called stomped normal (SN) distribution. The intensity distribution of a tissue class is represented by SN distribution, where each tissue class consists of a crisp lower approximation and a probabilistic boundary region. The intensity distribution of brain MR image is modeled as a mixture of finite number of SN distributions and one uniform distribution. The proposed method incorporates both the expectation-maximization and hidden Markov random field frameworks to provide an accurate and robust segmentation. The performance of the proposed approach, along with a comparison with related methods, is demonstrated on a set of synthetic and real brain MR images for different bias fields and noise levels.

Optical properties of mouse brain tissue after optical clearing with FocusClear™

NASA Astrophysics Data System (ADS)

Moy, Austin J.; Capulong, Bernard V.; Saager, Rolf B.; Wiersma, Matthew P.; Lo, Patrick C.; Durkin, Anthony J.; Choi, Bernard

2015-09-01

Fluorescence microscopy is commonly used to investigate disease progression in biological tissues. Biological tissues, however, are strongly scattering in the visible wavelengths, limiting the application of fluorescence microscopy to superficial (<200 μm) regions. Optical clearing, which involves incubation of the tissue in a chemical bath, reduces the optical scattering in tissue, resulting in increased tissue transparency and optical imaging depth. The goal of this study was to determine the time- and wavelength-resolved dynamics of the optical scattering properties of rodent brain after optical clearing with FocusClear™. Light transmittance and reflectance of 1-mm mouse brain sections were measured using an integrating sphere before and after optical clearing and the inverse adding doubling algorithm used to determine tissue optical scattering. The degree of optical clearing was quantified by calculating the optical clearing potential (OCP), and the effects of differing OCP were demonstrated using the optical histology method, which combines tissue optical clearing with optical imaging to visualize the microvasculature. We observed increased tissue transparency with longer optical clearing time and an analogous increase in OCP. Furthermore, OCP did not vary substantially between 400 and 1000 nm for increasing optical clearing durations, suggesting that optical histology can improve ex vivo visualization of several fluorescent probes.

Confocal laser endomicroscopy for brain tumor surgery: a milestone journey from microscopy to cellular surgery (Conference Presentation)

NASA Astrophysics Data System (ADS)

Charalampaki, Cleopatra

2017-02-01

The aim in brain tumor surgery is maximal tumor resection with minimal damage of normal neuronal tissue. Today diagnosis of tumor and definition of tumor borders intraoperatively is based on various visualization methods as well as on the histopathologic examination of a limited number of biopsy specimens via frozen sections. Unfortunately, intraoperative histopathology bears several shortcomings, and many biopsies are inconclusive. Therefore, the desirable treatment could be to have the ability to identify intraoperative cellular structures, and differentiate tumor from normal functional brain tissue on a cellular level. To achieve this goal new technological equipment integrated with new surgical concepts is needed.Confocal Laser Endomicroscopy (CLE) is an imaging technique which provides microscopic information of tissue in real-time. We are able to use these technique to perform intraoperative "optical biopsies" in bringing the microscope inside to the patients brain through miniaturized fiber-optic probes, and allow real-time histopathology. In our knowledge we are worldwide the only one neurosurgical group using CLE intraoperative for brain tumor surgery. We can detect and characterize intraoperative tumor cells, providing immediate online diagnosis without the need for frozen sections. It also provides delineation of borders between tumor and normal tissue on a cellular level, making surgical margins more accurate than ever before. The applications of CLE-assisted neurosurgery help to accurate the therapy by extending the resection borders and protecting the functionality of normal brain tissue in critical eloquent areas.

Hand in glove: brain and skull in development and dysmorphogenesis

PubMed Central

Flaherty, Kevin

2013-01-01

The brain originates relatively early in development from differentiated ectoderm that forms a hollow tube and takes on an exceedingly complex shape with development. The skull is made up of individual bony elements that form from neural crest- and mesoderm-derived mesenchyme that unite to provide support and protection for soft tissues and spaces of the head. The meninges provide a protective and permeable membrane between brain and skull. Across evolutionary and developmental time, dynamic changes in brain and skull shape track one another so that their integration is evidenced in two structures that fit soundly regardless of changes in biomechanical and physiologic functions. Evidence for this tight correspondence is also seen in diseases of the craniofacial complex that are often classified as diseases of the skull (e.g., craniosynostosis) or diseases of the brain (e.g., holoprosencephaly) even when both tissues are affected. Our review suggests a model that links brain and skull morphogenesis through coordinated integration of signaling pathways (e.g., FGF, TGFβ, Wnt) via processes that are not currently understood, perhaps involving the meninges. Differences in the earliest signaling of biological structure establish divergent designs that will be enhanced during morphogenesis. Signaling systems that pattern the developing brain are also active in patterning required for growth and assembly of the skull and some members of these signaling families have been indicated as causal for craniofacial diseases. Because cells of early brain and skull are sensitive to similar signaling families, variation in the strength or timing of signals or shifts in patterning boundaries that affect one system (neural or skull) could also affect the other system and appropriate co-adjustments in development would be made. Interactions of these signaling systems and of the tissues that they pattern are fundamental to the consistent but labile functional and structural association of brain and skull conserved over evolutionary time obvious in the study of development and disease. PMID:23525521

The Sun Health Research Institute Brain Donation Program: Description and Eexperience, 1987–2007

PubMed Central

Sue, Lucia I.; Walker, Douglas G.; Roher, Alex E.; Lue, LihFen; Vedders, Linda; Connor, Donald J.; Sabbagh, Marwan N.; Rogers, Joseph

2008-01-01

The Brain Donation Program at Sun Health Research Institute has been in continual operation since 1987, with over 1000 brains banked. The population studied primarily resides in the retirement communities of northwest metropolitan Phoenix, Arizona. The Institute is affiliated with Sun Health, a nonprofit community-owned and operated health care provider. Subjects are enrolled prospectively to allow standardized clinical assessments during life. Funding comes primarily from competitive grants. The Program has made short postmortem brain retrieval a priority, with a 2.75-h median postmortem interval for the entire collection. This maximizes the utility of the resource for molecular studies; frozen tissue from approximately 82% of all cases is suitable for RNA studies. Studies performed in-house have shown that, even with very short postmortem intervals, increasing delays in brain retrieval adversely affect RNA integrity and that cerebrospinal fluid pH increases with postmortem interval but does not predict tissue viability. PMID:18347928

The effects of 2.45 GHz radio frequency energy on neurological tissue genes using an unrestrained murine model in vivo

NASA Astrophysics Data System (ADS)

Stevens, Brandon William

The effects that radio frequency (RF) energy has on the body is currently an inconclusive and controversial topic. This is in part due to the differences and issues that can be found in previous studies. This thesis describes a study on the effect of continuous RF energy on the genome of in vivo mouse brain tissue for a duration of 31 days. To address the issues found in previous studies a new standardized procedure was followed. The genome of the brain tissue was quantified using RNA-seq and then analyzed using statistical combinations and empirical p-values. Transcripts with their respective p-values were uploaded into Integrity Pathway Analysis® to determine genes associated disease and function within the brain tissue. The results from this study provided evidence that supports RF energy induces changes in the genome. Additionally, the results provided evidence of the first reported case of a potential RF-controlled genetic transistor.

A Hybrid Hierarchical Approach for Brain Tissue Segmentation by Combining Brain Atlas and Least Square Support Vector Machine

PubMed Central

Kasiri, Keyvan; Kazemi, Kamran; Dehghani, Mohammad Javad; Helfroush, Mohammad Sadegh

2013-01-01

In this paper, we present a new semi-automatic brain tissue segmentation method based on a hybrid hierarchical approach that combines a brain atlas as a priori information and a least-square support vector machine (LS-SVM). The method consists of three steps. In the first two steps, the skull is removed and the cerebrospinal fluid (CSF) is extracted. These two steps are performed using the toolbox FMRIB's automated segmentation tool integrated in the FSL software (FSL-FAST) developed in Oxford Centre for functional MRI of the brain (FMRIB). Then, in the third step, the LS-SVM is used to segment grey matter (GM) and white matter (WM). The training samples for LS-SVM are selected from the registered brain atlas. The voxel intensities and spatial positions are selected as the two feature groups for training and test. SVM as a powerful discriminator is able to handle nonlinear classification problems; however, it cannot provide posterior probability. Thus, we use a sigmoid function to map the SVM output into probabilities. The proposed method is used to segment CSF, GM and WM from the simulated magnetic resonance imaging (MRI) using Brainweb MRI simulator and real data provided by Internet Brain Segmentation Repository. The semi-automatically segmented brain tissues were evaluated by comparing to the corresponding ground truth. The Dice and Jaccard similarity coefficients, sensitivity and specificity were calculated for the quantitative validation of the results. The quantitative results show that the proposed method segments brain tissues accurately with respect to corresponding ground truth. PMID:24696800

Stable microwave radiometry system for long term monitoring of deep tissue temperature

NASA Astrophysics Data System (ADS)

Stauffer, Paul R.; Rodriques, Dario B.; Salahi, Sara; Topsakal, Erdem; Oliveira, Tiago R.; Prakash, Aniruddh; D'Isidoro, Fabio; Reudink, Douglas; Snow, Brent W.; Maccarini, Paolo F.

2013-02-01

Background: There are numerous clinical applications for non-invasive monitoring of deep tissue temperature. We present the design and experimental performance of a miniature radiometric thermometry system for measuring volume average temperature of tissue regions located up to 5cm deep in the body. Methods: We constructed a miniature sensor consisting of EMI-shielded log spiral microstrip antenna with high gain onaxis and integrated high-sensitivity 1.35GHz total power radiometer with 500 MHz bandwidth. We tested performance of the radiometry system in both simulated and experimental multilayer phantom models of several intended clinical measurement sites: i) brown adipose tissue (BAT) depots within 2cm of the skin surface, ii) 3-5cm deep kidney, and iii) human brain underlying intact scalp and skull. The physical models included layers of circulating tissue-mimicking liquids controlled at different temperatures to characterize our ability to quantify small changes in target temperature at depth under normothermic surface tissues. Results: We report SAR patterns that characterize the sense region of a 2.6cm diameter receive antenna, and radiometric power measurements as a function of deep tissue temperature that quantify radiometer sensitivity. The data demonstrate: i) our ability to accurately track temperature rise in realistic tissue targets such as urine refluxed from prewarmed bladder into kidney, and 10°C drop in brain temperature underlying normothermic scalp and skull, and ii) long term accuracy and stability of +0.4°C over 4.5 hours as needed for monitoring core body temperature over extended surgery or monitoring effects of brown fat metabolism over an extended sleep/wake cycle. Conclusions: A non-invasive sensor consisting of 2.6cm diameter receive antenna and integral 1.35GHz total power radiometer has demonstrated sufficient sensitivity to track clinically significant changes in temperature of deep tissue targets underlying normothermic surface tissues for clinical applications like the detection of vesicoureteral reflux, and long term monitoring of brown fat metabolism or brain core temperature during extended surgery.

Stable Microwave Radiometry System for Long Term Monitoring of Deep Tissue Temperature.

PubMed

Stauffer, Paul R; Rodriques, Dario B; Salahi, Sara; Topsakal, Erdem; Oliveira, Tiago R; Prakash, Aniruddh; D'Isidoro, Fabio; Reudink, Douglas; Snow, Brent W; Maccarini, Paolo F

2013-02-26

There are numerous clinical applications for non-invasive monitoring of deep tissue temperature. We present the design and experimental performance of a miniature radiometric thermometry system for measuring volume average temperature of tissue regions located up to 5cm deep in the body. We constructed a miniature sensor consisting of EMI-shielded log spiral microstrip antenna with high gain on-axis and integrated high-sensitivity 1.35GHz total power radiometer with 500 MHz bandwidth. We tested performance of the radiometry system in both simulated and experimental multilayer phantom models of several intended clinical measurement sites: i) brown adipose tissue (BAT) depots within 2cm of the skin surface, ii) 3-5cm deep kidney, and iii) human brain underlying intact scalp and skull. The physical models included layers of circulating tissue-mimicking liquids controlled at different temperatures to characterize our ability to quantify small changes in target temperature at depth under normothermic surface tissues. We report SAR patterns that characterize the sense region of a 2.6cm diameter receive antenna, and radiometric power measurements as a function of deep tissue temperature that quantify radiometer sensitivity. The data demonstrate: i) our ability to accurately track temperature rise in realistic tissue targets such as urine refluxed from prewarmed bladder into kidney, and 10°C drop in brain temperature underlying normothermic scalp and skull, and ii) long term accuracy and stability of ∓0.4°C over 4.5 hours as needed for monitoring core body temperature over extended surgery or monitoring effects of brown fat metabolism over an extended sleep/wake cycle. A non-invasive sensor consisting of 2.6cm diameter receive antenna and integral 1.35GHz total power radiometer has demonstrated sufficient sensitivity to track clinically significant changes in temperature of deep tissue targets underlying normothermic surface tissues for clinical applications like the detection of vesicoureteral reflux, and long term monitoring of brown fat metabolism or brain core temperature during extended surgery.

Neurocognitive sparing of desktop microbeam irradiation.

PubMed

Bazyar, Soha; Inscoe, Christina R; Benefield, Thad; Zhang, Lei; Lu, Jianping; Zhou, Otto; Lee, Yueh Z

2017-08-11

Normal tissue toxicity is the dose-limiting side effect of radiotherapy. Spatial fractionation irradiation techniques, like microbeam radiotherapy (MRT), have shown promising results in sparing the normal brain tissue. Most MRT studies have been conducted at synchrotron facilities. With the aim to make this promising treatment more available, we have built the first desktop image-guided MRT device based on carbon nanotube x-ray technology. In the current study, our purpose was to evaluate the effects of MRT on the rodent normal brain tissue using our device and compare it with the effect of the integrated equivalent homogenous dose. Twenty-four, 8-week-old male C57BL/6 J mice were randomly assigned to three groups: MRT, broad-beam (BB) and sham. The hippocampal region was irradiated with two parallel microbeams in the MRT group (beam width = 300 μm, center-to-center = 900 μm, 160 kVp). The BB group received the equivalent integral dose in the same area of their brain. Rotarod, marble burying and open-field activity tests were done pre- and every month post-irradiation up until 8 months to evaluate the cognitive changes and potential irradiation side effects on normal brain tissue. The open-field activity test was substituted by Barnes maze test at 8th month. A multilevel model, random coefficients approach was used to evaluate the longitudinal and temporal differences among treatment groups. We found significant differences between BB group as compared to the microbeam-treated and sham mice in the number of buried marble and duration of the locomotion around the open-field arena than shams. Barnes maze revealed that BB mice had a lower capacity for spatial learning than MRT and shams. Mice in the BB group tend to gain weight at the slower pace than shams. No meaningful differences were found between MRT and sham up until 8-month follow-up using our measurements. Applying MRT with our newly developed prototype compact CNT-based image-guided MRT system utilizing the current irradiation protocol can better preserve the integrity of normal brain tissue. Consequently, it enables applying higher irradiation dose that promises better tumor control. Further studies are required to evaluate the full extent effects of this novel modality.

Metabolomics and neuroanatomical evaluation of post-mortem changes in the hippocampus.

PubMed

Gonzalez-Riano, Carolina; Tapia-González, Silvia; García, Antonia; Muñoz, Alberto; DeFelipe, Javier; Barbas, Coral

2017-08-01

Understanding the human brain is the ultimate goal in neuroscience, but this is extremely challenging in part due to the fact that brain tissue obtained from autopsy is practically the only source of normal brain tissue and also since changes at different levels of biological organization (genetic, molecular, biochemical, anatomical) occur after death due to multiple mechanisms. Here we used metabolomic and anatomical techniques to study the possible relationship between post-mortem time (PT)-induced changes that may occur at both the metabolomics and anatomical levels in the same brains. Our experiments have mainly focused on the hippocampus of the mouse. We found significant metabolomic changes at 2 h PT, whereas the integrity of neurons and glia, at the anatomical/ neurochemical level, was not significantly altered during the first 5 h PT for the majority of histological markers.

The Kringle-2 domain of tissue plasminogen activator significantly reduces mortality and brain infarction in middle cerebral artery occlusion rats.

PubMed

Zhang, Haitao; Bi, Feng; Xiao, Chunlan; Liu, Jianxia; Wang, Zhixia; Liu, Jian-Ning; Zhang, Jing

2010-08-01

Tissue plasminogen activator (TPA) showed brain-protective activity within the first 15 min after cerebral ischemia in rats. To understand its molecular mechanism, TPA derivates were intracerebroventricularly administered at 15 min before, and 15, 90, 120 min after middle cerebral artery occlusion (MCAO) in rats. The reduction in mortality and cerebral infarction at 24 h was seen only with TPA administered at 15 min after MCAO. The down-regulation of endogenous TPA by the intracerebroventricular injection of TPA was found to be responsible for the protective effect on the integrity of blood-brain barrier after MCAO, as well as for the reduction in mortality and cerebral infarction. Moreover, for the first time we have found that the Kringle-2 domain is essential for the brain-protective activity of TPA.

A non-aggressive, highly efficient, enzymatic method for dissociation of human brain-tumors and brain-tissues to viable single-cells.

PubMed

Volovitz, Ilan; Shapira, Netanel; Ezer, Haim; Gafni, Aviv; Lustgarten, Merav; Alter, Tal; Ben-Horin, Idan; Barzilai, Ori; Shahar, Tal; Kanner, Andrew; Fried, Itzhak; Veshchev, Igor; Grossman, Rachel; Ram, Zvi

2016-06-01

Conducting research on the molecular biology, immunology, and physiology of brain tumors (BTs) and primary brain tissues requires the use of viably dissociated single cells. Inadequate methods for tissue dissociation generate considerable loss in the quantity of single cells produced and in the produced cells' viability. Improper dissociation may also demote the quality of data attained in functional and molecular assays due to the presence of large quantities cellular debris containing immune-activatory danger associated molecular patterns, and due to the increased quantities of degraded proteins and RNA. Over 40 resected BTs and non-tumorous brain tissue samples were dissociated into single cells by mechanical dissociation or by mechanical and enzymatic dissociation. The quality of dissociation was compared for all frequently used dissociation enzymes (collagenase, DNase, hyaluronidase, papain, dispase) and for neutral protease (NP) from Clostridium histolyticum. Single-cell-dissociated cell mixtures were evaluated for cellular viability and for the cell-mixture dissociation quality. Dissociation quality was graded by the quantity of subcellular debris, non-dissociated cell clumps, and DNA released from dead cells. Of all enzymes or enzyme combinations examined, NP (an enzyme previously not evaluated on brain tissues) produced dissociated cell mixtures with the highest mean cellular viability: 93 % in gliomas, 85 % in brain metastases, and 89 % in non-tumorous brain tissue. NP also produced cell mixtures with significantly less cellular debris than other enzymes tested. Dissociation using NP was non-aggressive over time-no changes in cell viability or dissociation quality were found when comparing 2-h dissociation at 37 °C to overnight dissociation at ambient temperature. The use of NP allows for the most effective dissociation of viable single cells from human BTs or brain tissue. Its non-aggressive dissociative capacity may enable ambient-temperature shipping of tumor pieces in multi-center clinical trials, meanwhile being dissociated. As clinical grade NP is commercially available it can be easily integrated into cell-therapy clinical trials in neuro-oncology. The high quality viable cells produced may enable investigators to conduct more consistent research by avoiding the experimental artifacts associated with the presence dead cells or cellular debris.

Development of stereotactic mass spectrometry for brain tumor surgery.

PubMed

Agar, Nathalie Y R; Golby, Alexandra J; Ligon, Keith L; Norton, Isaiah; Mohan, Vandana; Wiseman, Justin M; Tannenbaum, Allen; Jolesz, Ferenc A

2011-02-01

Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue. To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents. Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity. Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence. The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of any organ and with a rapidity that allows real-time analysis.

Deep Convolutional Neural Networks for Multi-Modality Isointense Infant Brain Image Segmentation

PubMed Central

Zhang, Wenlu; Li, Rongjian; Deng, Houtao; Wang, Li; Lin, Weili; Ji, Shuiwang; Shen, Dinggang

2015-01-01

The segmentation of infant brain tissue images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) plays an important role in studying early brain development in health and disease. In the isointense stage (approximately 6–8 months of age), WM and GM exhibit similar levels of intensity in both T1 and T2 MR images, making the tissue segmentation very challenging. Only a small number of existing methods have been designed for tissue segmentation in this isointense stage; however, they only used a single T1 or T2 images, or the combination of T1 and T2 images. In this paper, we propose to use deep convolutional neural networks (CNNs) for segmenting isointense stage brain tissues using multi-modality MR images. CNNs are a type of deep models in which trainable filters and local neighborhood pooling operations are applied alternatingly on the raw input images, resulting in a hierarchy of increasingly complex features. Specifically, we used multimodality information from T1, T2, and fractional anisotropy (FA) images as inputs and then generated the segmentation maps as outputs. The multiple intermediate layers applied convolution, pooling, normalization, and other operations to capture the highly nonlinear mappings between inputs and outputs. We compared the performance of our approach with that of the commonly used segmentation methods on a set of manually segmented isointense stage brain images. Results showed that our proposed model significantly outperformed prior methods on infant brain tissue segmentation. In addition, our results indicated that integration of multi-modality images led to significant performance improvement. PMID:25562829

Tissue and organ donation for research in forensic pathology: the MRC Sudden Death Brain and Tissue Bank.

PubMed

Millar, T; Walker, R; Arango, J-C; Ironside, J W; Harrison, D J; MacIntyre, D J; Blackwood, D; Smith, C; Bell, J E

2007-12-01

Novel methodological approaches to the investigation of brain and non-central nervous system disorders have led to increased demand for well-characterized, high quality human tissue samples, particularly from control cases. In the setting of the new Human Tissue legislation, we sought to determine whether relatives who have been suddenly bereaved are willing to grant authorization for research use of post mortem tissue samples and organs in sufficient numbers to support the establishment of a brain and tissue bank based in the forensic service. Research authorization was sought from families on the day prior to forensic post mortem examination followed up by written confirmation. We have to date selected individuals who have died suddenly (age range 1-89 years) and who were likely to have normal brains or who had displayed symptoms of a CNS disorder of interest to researchers, including psychiatric disorders. One hundred and eleven families have been approached during the first 2 years of this project. Research use of tissue samples was authorized by 96% of families and 17% agreed to whole brain donation. Audit of families' experience does not suggest that they are further distressed by being approached. Respondents expressed a clear view that the opportunity for research donation should be open to all bereaved families. Despite the sometimes long post mortem intervals, the quality of tissue samples is good, as assessed by a range of markers including Agilent BioAnalyzer quantification of RNA integrity (mean value 6.4). We conclude that the vast majority of families are willing to support research use of post mortem tissues even in the context of sudden bereavement and despite previous adverse publicity. The potential for acquisition of normal CNS and non-CNS tissues and of various hard-to-get CNS disorders suggests that efforts to access the forensic post mortem service for research material are eminently worthwhile. (c) 2007 Pathological Society of Great Britain and Ireland

Rheological effects of drag-reducing polymers improve cerebral blood flow and oxygenation after traumatic brain injury in rats.

PubMed

Bragin, Denis E; Kameneva, Marina V; Bragina, Olga A; Thomson, Susan; Statom, Gloria L; Lara, Devon A; Yang, Yirong; Nemoto, Edwin M

2017-03-01

Cerebral ischemia has been clearly demonstrated after traumatic brain injury (TBI); however, neuroprotective therapies have not focused on improvement of the cerebral microcirculation. Blood soluble drag-reducing polymers (DRP), prepared from high molecular weight polyethylene oxide, target impaired microvascular perfusion by altering the rheological properties of blood and, until our recent reports, has not been applied to the brain. We hypothesized that DRP improve cerebral microcirculation and oxygenation after TBI. DRP were studied in healthy and traumatized rat brains and compared to saline controls. Using in-vivo two-photon laser scanning microscopy over the parietal cortex, we showed that after TBI, nanomolar concentrations of intravascular DRP significantly enhanced microvascular perfusion and tissue oxygenation in peri-contusional areas, preserved blood-brain barrier integrity and protected neurons. The mechanisms of DRP effects were attributable to reduction of the near-vessel wall cell-free layer which increased near-wall blood flow velocity, microcirculatory volume flow, and number of erythrocytes entering capillaries, thereby reducing capillary stasis and tissue hypoxia as reflected by a reduction in NADH. Our results indicate that early reduction in CBF after TBI is mainly due to ischemia; however, metabolic depression of contused tissue could be also involved.

Rough-Fuzzy Clustering and Unsupervised Feature Selection for Wavelet Based MR Image Segmentation

PubMed Central

Maji, Pradipta; Roy, Shaswati

2015-01-01

Image segmentation is an indispensable process in the visualization of human tissues, particularly during clinical analysis of brain magnetic resonance (MR) images. For many human experts, manual segmentation is a difficult and time consuming task, which makes an automated brain MR image segmentation method desirable. In this regard, this paper presents a new segmentation method for brain MR images, integrating judiciously the merits of rough-fuzzy computing and multiresolution image analysis technique. The proposed method assumes that the major brain tissues, namely, gray matter, white matter, and cerebrospinal fluid from the MR images are considered to have different textural properties. The dyadic wavelet analysis is used to extract the scale-space feature vector for each pixel, while the rough-fuzzy clustering is used to address the uncertainty problem of brain MR image segmentation. An unsupervised feature selection method is introduced, based on maximum relevance-maximum significance criterion, to select relevant and significant textural features for segmentation problem, while the mathematical morphology based skull stripping preprocessing step is proposed to remove the non-cerebral tissues like skull. The performance of the proposed method, along with a comparison with related approaches, is demonstrated on a set of synthetic and real brain MR images using standard validity indices. PMID:25848961

Integrity of normal-appearing white matter: Influence of age, visible lesion burden and hypertension in patients with small-vessel disease.

PubMed

Muñoz Maniega, Susana; Chappell, Francesca M; Valdés Hernández, Maria C; Armitage, Paul A; Makin, Stephen D; Heye, Anna K; Thrippleton, Michael J; Sakka, Eleni; Shuler, Kirsten; Dennis, Martin S; Wardlaw, Joanna M

2017-02-01

White matter hyperintensities accumulate with age and occur in patients with stroke, but their pathogenesis is poorly understood. We measured multiple magnetic resonance imaging biomarkers of tissue integrity in normal-appearing white matter and white matter hyperintensities in patients with mild stroke, to improve understanding of white matter hyperintensities origins. We classified white matter into white matter hyperintensities and normal-appearing white matter and measured fractional anisotropy, mean diffusivity, water content (T1-relaxation time) and blood-brain barrier leakage (signal enhancement slope from dynamic contrast-enhanced magnetic resonance imaging). We studied the effects of age, white matter hyperintensities burden (Fazekas score) and vascular risk factors on each biomarker, in normal-appearing white matter and white matter hyperintensities, and performed receiver-operator characteristic curve analysis. Amongst 204 patients (34.3-90.9 years), all biomarkers differed between normal-appearing white matter and white matter hyperintensities ( P < 0.001). In normal-appearing white matter and white matter hyperintensities, mean diffusivity and T1 increased with age ( P < 0.001), all biomarkers varied with white matter hyperintensities burden ( P < 0.001; P = 0.02 signal enhancement slope), but only signal enhancement slope increased with hypertension ( P = 0.028). Fractional anisotropy showed complex age-white matter hyperintensities-tissue interactions; enhancement slope showed white matter hyperintensities-tissue interactions. Mean diffusivity distinguished white matter hyperintensities from normal-appearing white matter best at all ages. Blood-brain barrier leakage increases with hypertension and white matter hyperintensities burden at all ages in normal-appearing white matter and white matter hyperintensities, whereas water mobility and content increase as tissue damage accrues, suggesting that blood-brain barrier leakage mediates small vessel disease-related brain damage.

Epsilon Aminocaproic Acid Pretreatment Provides Neuroprotection Following Surgically Induced Brain Injury in a Rat Model.

PubMed

Komanapalli, Esther S; Sherchan, Prativa; Rolland, William; Khatibi, Nikan; Martin, Robert D; Applegate, Richard L; Tang, Jiping; Zhang, John H

2016-01-01

Neurosurgical procedures can damage viable brain tissue unintentionally by a wide range of mechanisms. This surgically induced brain injury (SBI) can be a result of direct incision, electrocauterization, or tissue retraction. Plasmin, a serine protease that dissolves fibrin blood clots, has been shown to enhance cerebral edema and hemorrhage accumulation in the brain through disruption of the blood brain barrier. Epsilon aminocaproic acid (EAA), a recognized antifibrinolytic lysine analogue, can reduce the levels of active plasmin and, in doing so, potentially can preserve the neurovascular unit of the brain. We investigated the role of EAA as a pretreatment neuroprotective modality in a SBI rat model, hypothesizing that EAA therapy would protect brain tissue integrity, translating into preserved neurobehavioral function. Male Sprague-Dawley rats were randomly assigned to one of four groups: sham (n = 7), SBI (n = 7), SBI with low-dose EAA, 150 mg/kg (n = 7), and SBI with high-dose EAA, 450 mg/kg (n = 7). SBI was induced by partial right frontal lobe resection through a frontal craniotomy. Postoperative assessment at 24 h included neurobehavioral testing and measurement of brain water content. Results at 24 h showed both low- and high-dose EAA reduced brain water content and improved neurobehavioral function compared with the SBI groups. This suggests that EAA may be a useful pretherapeutic modality for SBI. Further studies are needed to clarify optimal therapeutic dosing and to identify mechanisms of neuroprotection in rat SBI models.

Neural networks improve brain cancer detection with Raman spectroscopy in the presence of light artifacts

NASA Astrophysics Data System (ADS)

Jermyn, Michael; Desroches, Joannie; Mercier, Jeanne; St-Arnaud, Karl; Guiot, Marie-Christine; Petrecca, Kevin; Leblond, Frederic

2016-03-01

It is often difficult to identify cancer tissue during brain cancer (glioma) surgery. Gliomas invade into areas of normal brain, and this cancer invasion is frequently not detected using standard preoperative magnetic resonance imaging (MRI). This results in enduring invasive cancer following surgery and leads to recurrence. A hand-held Raman spectroscopy is able to rapidly detect cancer invasion in patients with grade 2-4 gliomas. However, ambient light sources can produce spectral artifacts which inhibit the ability to distinguish between cancer and normal tissue using the spectral information available. To address this issue, we have demonstrated that artificial neural networks (ANN) can accurately classify invasive cancer versus normal brain tissue, even when including measurements with significant spectral artifacts from external light sources. The non-parametric and adaptive model used by ANN makes it suitable for detecting complex non-linear spectral characteristics associated with different tissues and the confounding presence of light artifacts. The use of ANN for brain cancer detection with Raman spectroscopy, in the presence of light artifacts, improves the robustness and clinical translation potential for intraoperative use. Integration with the neurosurgical workflow is facilitated by accounting for the effect of light artifacts which may occur, due to operating room lights, neuronavigation systems, windows, or other light sources. The ability to rapidly detect invasive brain cancer under these conditions may reduce residual cancer remaining after surgery, and thereby improve patient survival.

Relationship between time-resolved and non-time-resolved Beer-Lambert law in turbid media.

PubMed

Nomura, Y; Hazeki, O; Tamura, M

1997-06-01

The time-resolved Beer-Lambert law proposed for oxygen monitoring using pulsed light was extended to the non-time-resolved case in a scattered medium such as living tissues with continuous illumination. The time-resolved Beer-Lambert law was valid for the phantom model and living tissues in the visible and near-infrared regions. The absolute concentration and oxygen saturation of haemoglobin in rat brain and thigh muscle could be determined. The temporal profile of rat brain was reproduced by Monte Carlo simulation. When the temporal profiles of rat brain under different oxygenation states were integrated with time, the absorbance difference was linearly related to changes in the absorption coefficient. When the simulated profiles were integrated, there was a linear relationship within the absorption coefficient which was predicted for fractional inspiratory oxygen concentration from 10 to 100% and, in the case beyond the range of the absorption coefficient, the deviation from linearity was slight. We concluded that an optical pathlength which is independent of changes in the absorption coefficient is a good approximation for near-infrared oxygen monitoring.

Exendin-4 inhibits high-altitude cerebral edema by protecting against neurobiological dysfunction

PubMed Central

Sun, Zhong-Lei; Jiang, Xian-Feng; Cheng, Yuan-Chi; Liu, Ying-Fu; Yang, Kai; Zhu, Shuang-Long; Kong, Xian-Bin; Tu, Yue; Bian, Ke-Feng; Liu, Zhen-Lin; Chen, Xu-Yi

2018-01-01

The anti-inflammatory and antioxidant effects of exendin-4 (Ex-4) have been reported previously. However, whether (Ex-4) has anti-inflammatory and antioxidant effects on high-altitude cerebral edema (HACE) remains poorly understood. In this study, two rat models of HACE were established by placing rats in a hypoxic environment with a simulated altitude of either 6000- or 7000-m above sea level (MASL) for 72 hours. An altitude of 7000 MASL with 72-hours of hypoxia was found to be the optimized experimental paradigm for establishing HACE models. Then, in rats where a model of HACE was established by introducing them to a 7000 MASL environment with 72-hours of hypoxia treatment, 2, 10 and, 100 μg of Ex-4 was intraperitoneally administrated. The open field test and tail suspension test were used to test animal behavior. Routine methods were used to detect change in inflammatory cells. Hematoxylin-eosin staining was performed to determine pathological changes to brain tissue. Wet/dry weight ratios were used to measure brain water content. Evans blue leakage was used to determine blood-brain barrier integrity. Enzyme-linked immunosorbent assay (ELISA) was performed to measure markers of inflammation and oxidative stress including superoxide dismutase, glutathione, and malonaldehyde values, as well as interleukin-6, tumor necrosis factor-alpha, cyclic adenosine monophosphate levels in the brain tissue. Western blot analysis was performed to determine the levels of occludin, ZO-1, SOCS-3, vascular endothelial growth factor, EPAC1, nuclear factor-kappa B, and aquaporin-4. Our results demonstrate that Ex-4 preconditioning decreased brain water content, inhibited inflammation and oxidative stress, alleviated brain tissue injury, maintain blood-brain barrier integrity, and effectively improved motor function in rat models of HACE. These findings suggest that Ex-4 exhibits therapeutic potential in the treatment of HACE. PMID:29722317

Markers for human brain pericytes and smooth muscle cells.

PubMed

Smyth, Leon C D; Rustenhoven, Justin; Scotter, Emma L; Schweder, Patrick; Faull, Richard L M; Park, Thomas I H; Dragunow, Mike

2018-06-07

Brain pericytes and vascular smooth muscle cells (vSMCs) are a critical component of the neurovascular unit and are important in regulating cerebral blood flow and blood-brain barrier integrity. Identification of subtypes of mural cells in tissue and in vitro is important to any study of their function, therefore we identified distinct mural cell morphologies in neurologically normal post-mortem human brain. Further, the distribution of mural cell markers platelet-derived growth factor receptor-β (PDGFRβ), α-smooth muscle actin (αSMA), CD13, neural/glial antigen-2 (NG2), CD146 and desmin was examined. We determined that PDGFRβ, NG2, CD13, and CD146 were expressed in capillary-associated pericytes. NG2, and CD13 were also present on vSMCs in large vessels, however abundant CD146 and desmin staining was also detected in vSMCs on large vessels, co-labelling with αSMA. To determine whether cultures recapitulated observations from tissue, primary human brain pericytes derived from neurologically normal autopsies were analysed for the presence of pericyte markers by immunocytochemistry, western blotting and qPCR. The proteins observed in brain pericytes in tissue (PDGFRβ, αSMA, desmin, CD146, CD13, and NG2) were present in vitro, validating a panel of proteins that can be used to label brain pericytes and vSMCs in tissue and in vitro. Finally, we showed that the proteins CD146 and desmin that are expressed on large vessels in situ, are also selective markers of a smooth muscle cell phenotype in vitro. Copyright © 2018 Elsevier B.V. All rights reserved.

Prediction of specific damage or infarction from the measurement of tissue impedance following repetitive brain ischaemia in the rat.

PubMed

Klein, H C; Krop-Van Gastel, W; Go, K G; Korf, J

1993-02-01

The development of irreversible brain damage during repetitive periods of hypoxia and normoxia was studied in anaesthetized rats with unilateral occlusion of the carotid artery (modified Levine model). Rats were exposed to 10 min hypoxia and normoxia until severe damage developed. As indices of damage, whole striatal tissue impedance (reflecting cellular water uptake), sodium/potassium contents (due to exchange with blood). Evans Blue staining (blood-brain barrier [BBB] integrity) and silver staining (increased in irreversibly damaged neurons) were used. A substantial decrease in blood pressure was observed during the hypoxic periods possibly producing severe ischaemia. Irreversibly increased impedance, massive changes in silver staining, accumulation of whole tissue Na and loss of K occurred only after a minimum of two periods of hypoxia, but there was no disruption of the BBB. Microscopic examination of tissue sections revealed that cell death was selective with reversible impedance changes, but became massive and non-specific after irreversible increase of the impedance. The development of brain infarcts could, however, not be predicted from measurements of physiological parameters in the blood. We suggest that the development of cerebral infarction during repetitive periods of hypoxia may serve as a model for the development of brain damage in a variety of clinical conditions. Furthermore, the present model allows the screening of potential therapeutic measuring of the prevention and treatment of both infarction and selective cell death.

A Novel Semi-Supervised Methodology for Extracting Tumor Type-Specific MRS Sources in Human Brain Data

PubMed Central

Ortega-Martorell, Sandra; Ruiz, Héctor; Vellido, Alfredo; Olier, Iván; Romero, Enrique; Julià-Sapé, Margarida; Martín, José D.; Jarman, Ian H.; Arús, Carles; Lisboa, Paulo J. G.

2013-01-01

Background The clinical investigation of human brain tumors often starts with a non-invasive imaging study, providing information about the tumor extent and location, but little insight into the biochemistry of the analyzed tissue. Magnetic Resonance Spectroscopy can complement imaging by supplying a metabolic fingerprint of the tissue. This study analyzes single-voxel magnetic resonance spectra, which represent signal information in the frequency domain. Given that a single voxel may contain a heterogeneous mix of tissues, signal source identification is a relevant challenge for the problem of tumor type classification from the spectroscopic signal. Methodology/Principal Findings Non-negative matrix factorization techniques have recently shown their potential for the identification of meaningful sources from brain tissue spectroscopy data. In this study, we use a convex variant of these methods that is capable of handling negatively-valued data and generating sources that can be interpreted as tumor class prototypes. A novel approach to convex non-negative matrix factorization is proposed, in which prior knowledge about class information is utilized in model optimization. Class-specific information is integrated into this semi-supervised process by setting the metric of a latent variable space where the matrix factorization is carried out. The reported experimental study comprises 196 cases from different tumor types drawn from two international, multi-center databases. The results indicate that the proposed approach outperforms a purely unsupervised process by achieving near perfect correlation of the extracted sources with the mean spectra of the tumor types. It also improves tissue type classification. Conclusions/Significance We show that source extraction by unsupervised matrix factorization benefits from the integration of the available class information, so operating in a semi-supervised learning manner, for discriminative source identification and brain tumor labeling from single-voxel spectroscopy data. We are confident that the proposed methodology has wider applicability for biomedical signal processing. PMID:24376744

A multi-tissue type genome-scale metabolic network for analysis of whole-body systems physiology

PubMed Central

2011-01-01

Background Genome-scale metabolic reconstructions provide a biologically meaningful mechanistic basis for the genotype-phenotype relationship. The global human metabolic network, termed Recon 1, has recently been reconstructed allowing the systems analysis of human metabolic physiology and pathology. Utilizing high-throughput data, Recon 1 has recently been tailored to different cells and tissues, including the liver, kidney, brain, and alveolar macrophage. These models have shown utility in the study of systems medicine. However, no integrated analysis between human tissues has been done. Results To describe tissue-specific functions, Recon 1 was tailored to describe metabolism in three human cells: adipocytes, hepatocytes, and myocytes. These cell-specific networks were manually curated and validated based on known cellular metabolic functions. To study intercellular interactions, a novel multi-tissue type modeling approach was developed to integrate the metabolic functions for the three cell types, and subsequently used to simulate known integrated metabolic cycles. In addition, the multi-tissue model was used to study diabetes: a pathology with systemic properties. High-throughput data was integrated with the network to determine differential metabolic activity between obese and type II obese gastric bypass patients in a whole-body context. Conclusion The multi-tissue type modeling approach presented provides a platform to study integrated metabolic states. As more cell and tissue-specific models are released, it is critical to develop a framework in which to study their interdependencies. PMID:22041191

HISTOLOGICAL STUDIES OF THE EFFECTS OF CHRONIC IMPLANTATION OF CERAMIC-BASED MICROELECTRODE ARRAYS AND MICRODIALYSIS PROBES IN RAT PREFRONTAL CORTEX

PubMed Central

Hascup, Erin R.; Bjerkén, Sara af; Hascup, Kevin N.; Pomerleau, Francois; Huettl, Peter; Strömberg, Ingrid; Gerhardt, Greg A.

2010-01-01

Chronic implantation of neurotransmitter measuring devices is essential for awake, behavioral studies occurring over multiple days. Little is known regarding the effects of long term implantation on surrounding brain parenchyma and the resulting alterations in the functional properties of this tissue. We examined the extent of tissue damage produced by chronic implantation of either ceramic microelectrode arrays (MEAs) or microdialysis probes. Histological studies were carried out on fixed tissues using stains for neurons (cresyl violet), astrocytes (GFAP), microglia (Iba-1), glutamatergic nerve fibers (VGLUT1), and the blood-brain barrier (SMI-71). Nissl staining showed pronounced tissue body loss with microdialysis implants compared to MEAs. The MEAs produced mild gliosis extending 50–100 µm from the tracks, with a significant change in the affected areas starting at 3 days. By contrast, the microdialysis probes produced gliosis extending 200–300 µm from the track, which was significant at 3 and 7 days. Markers for microglia and glutamatergic fibers supported that the MEAs produce minimal damage with significant changes occurring only at 3 and 7 days that return to control levels by one month. SMI-71 staining supported integrity of the blood brain barrier out to 1 week for both the microdialysis probes and the MEAs. This data support that the ceramic MEAs small size and biocompatibility are necessary to accurately measure neurotransmitter levels in the intact brain. The minimal invasiveness of the MEAs reduce tissue loss, allowing for long term (>6 month) electrochemical and electrophysiological monitoring of brain activity. PMID:19577548

ABERRANT SPLICING OF A BRAIN-ENRICHED ALTERNATIVE EXON ELIMINATES TUMOR SUPPRESSOR FUNCTION AND PROMOTES ONCOGENE FUNCTION DURING BRAIN TUMORIGENESIS

PubMed Central

Bredel, Markus; Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; Elverfeldt, Dominik v.; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.

2014-01-01

BACKGROUND: Tissue-specific alternative splicing is known to be critical to emergence of tissue identity during development, yet its role in malignant transformation is undefined. Tissue-specific splicing involves evolutionary-conserved, alternative exons, which represent only a minority of total alternative exons. Many, however, have functional features that influence activity in signaling pathways to profound biological effect. Given that tissue-specific splicing has a determinative role in brain development and the enrichment of genes containing tissue-specific exons for proteins with roles in signaling and development, it is thus plausible that changes in such exons could rewire normal neurogenesis towards malignant transformation. METHODS: We used integrated molecular genetic and cell biology analyses, computational biology, animal modeling, and clinical patient profiles to characterize the effect of aberrant splicing of a brain-enriched alternative exon in the membrane-binding tumor suppressor Annexin A7 (ANXA7) on oncogene regulation and brain tumorigenesis. RESULTS: We show that aberrant splicing of a tissue-specific cassette exon in ANXA7 diminishes endosomal targeting and consequent termination of the signal of the EGFR oncoprotein during brain tumorigenesis. Splicing of this exon is mediated by the ribonucleoprotein Polypyrimidine Tract-Binding Protein 1 (PTBP1), which is normally repressed during brain development but, we find, is excessively expressed in glioblastomas through either gene amplification or loss of a neuron-specific microRNA, miR-124. Silencing of PTBP1 attenuates both malignancy and angiogenesis in a stem cell-derived glioblastoma animal model characterized by a high native propensity to generate tumor endothelium or vascular pericytes to support tumor growth. We show that EGFR amplification and PTBP1 overexpression portend a similarly poor clinical outcome, further highlighting the importance of PTBP1-mediated activation of EGFR. CONCLUSIONS: Our data illustrate how anomalous splicing of a tissue-regulated exon in a constituent of an oncogenic signaling pathway eliminates its tumor suppressor function and promotes tumorigenesis. This paradigm of malignant glial transformation as a consequence of tissue-specific alternative exon splicing in a tumor suppressor, may have widespread applicability in explaining how changes in critical tissue-specific regulatory mechanisms reprogram normal development to oncogenesis. SECONDARY CATEGORY: n/a.

A Nth-order linear algorithm for extracting diffuse correlation spectroscopy blood flow indices in heterogeneous tissues.

PubMed

Shang, Yu; Yu, Guoqiang

2014-09-29

Conventional semi-infinite analytical solutions of correlation diffusion equation may lead to errors when calculating blood flow index (BFI) from diffuse correlation spectroscopy (DCS) measurements in tissues with irregular geometries. Very recently, we created an algorithm integrating a N th-order linear model of autocorrelation function with the Monte Carlo simulation of photon migrations in homogenous tissues with arbitrary geometries for extraction of BFI (i.e., αD B ). The purpose of this study is to extend the capability of the N th-order linear algorithm for extracting BFI in heterogeneous tissues with arbitrary geometries. The previous linear algorithm was modified to extract BFIs in different types of tissues simultaneously through utilizing DCS data at multiple source-detector separations. We compared the proposed linear algorithm with the semi-infinite homogenous solution in a computer model of adult head with heterogeneous tissue layers of scalp, skull, cerebrospinal fluid, and brain. To test the capability of the linear algorithm for extracting relative changes of cerebral blood flow (rCBF) in deep brain, we assigned ten levels of αD B in the brain layer with a step decrement of 10% while maintaining αD B values constant in other layers. Simulation results demonstrate the accuracy (errors < 3%) of high-order ( N  ≥ 5) linear algorithm in extracting BFIs in different tissue layers and rCBF in deep brain. By contrast, the semi-infinite homogenous solution resulted in substantial errors in rCBF (34.5% ≤ errors ≤ 60.2%) and BFIs in different layers. The N th-order linear model simplifies data analysis, thus allowing for online data processing and displaying. Future study will test this linear algorithm in heterogeneous tissues with different levels of blood flow variations and noises.

A simple cell transport device keeps culture alive and functional during shipping.

PubMed

Miller, Paula G; Wang, Ying I; Swan, Glen; Shuler, Michael L

2017-09-01

Transporting living complex cellular constructs through the mail while retaining their full viability and functionality is challenging. During this process, cells often suffer from exposure to suboptimal life-sustaining conditions (e.g. temperature, pH), as well as damage due to shear stress. We have developed a transport device for shipping intact cell/tissue constructs from one facility to another that overcomes these obstacles. Our transport device maintained three different cell lines (Caco2, A549, and HepG2 C3A) individually on transwell membranes with high viability (above 97%) for 48 h under simulated shipping conditions without an incubator. The device was also tested by actual overnight shipping of blood brain barrier constructs consisting of human induced pluripotent brain microvascular endothelial cells and rat astrocytes on transwell membranes to a remote facility (approximately 1200 miles away). The blood brain barrier constructs arrived with high cell viability and were able to regain full barrier integrity after equilibrating in the incubator for 24 h; this was assessed by the presence of continuous tight junction networks and in vivo-like values for trans-endothelial electrical resistance (TEER). These results demonstrated that our cell transport device could be a useful tool for long-distance transport of membrane-bound cell cultures and functional tissue constructs. Studies that involve various cell and tissue constructs, such as the "Multi-Organ-on-Chip" devices (where multiple microscale tissue constructs are integrated on a single microfluidic device) and studies that involve microenvironments where multiple tissue interactions are of interest, would benefit from the ability to transport or receive these constructs. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1257-1266, 2017. © 2017 American Institute of Chemical Engineers.

In vivo detection of microstructural correlates of brain pathology in preclinical and early Alzheimer Disease with magnetic resonance imaging.

PubMed

Zhao, Yue; Raichle, Marcus E; Wen, Jie; Benzinger, Tammie L; Fagan, Anne M; Hassenstab, Jason; Vlassenko, Andrei G; Luo, Jie; Cairns, Nigel J; Christensen, Jon J; Morris, John C; Yablonskiy, Dmitriy A

2017-03-01

Alzheimer disease (AD) affects at least 5 million individuals in the USA alone stimulating an intense search for disease prevention and treatment therapies as well as for diagnostic techniques allowing early identification of AD during a long pre-symptomatic period that can be used for the initiation of prevention trials of disease-modifying therapies in asymptomatic individuals. Our approach to developing such techniques is based on the Gradient Echo Plural Contrast Imaging (GEPCI) technique that provides quantitative in vivo measurements of several brain-tissue-specific characteristics of the gradient echo MRI signal (GEPCI metrics) that depend on the integrity of brain tissue cellular structure. Preliminary data were obtained from 34 participants selected from the studies of aging and dementia at the Knight Alzheimer's Disease Research Center at Washington University in St. Louis. Cognitive status was operationalized with the Clinical Dementia Rating (CDR) scale. The participants, assessed as cognitively normal (CDR=0; n=23) or with mild AD dementia (CDR=0.5 or 1; n=11) underwent GEPCI MRI, a collection of cognitive performance tests and CSF amyloid (Aβ) biomarker Aβ 42 . A subset of 19 participants also underwent PET PiB studies to assess their brain Aβ burden. According to the Aβ status, cognitively normal participants were divided into normal (Aβ negative; n=13) and preclinical (Aβ positive; n=10) groups. GEPCI quantitative measurements demonstrated significant differences between all the groups: normal and preclinical, normal and mild AD, and preclinical and mild AD. GEPCI quantitative metrics characterizing tissue cellular integrity in the hippocampus demonstrated much stronger correlations with psychometric tests than the hippocampal atrophy. Importantly, GEPCI-determined changes in the hippocampal tissue cellular integrity were detected even in the hippocampal areas not affected by the atrophy. Our studies also uncovered strong correlations between GEPCI brain tissue metrics and beta-amyloid (Aβ) burden defined by positron emission tomography (PET) - the current in vivo gold standard for detection of cortical Aβ, thus supporting GEPCI as a potential surrogate marker for Aβ imaging - a known biomarker of early AD. Remarkably, the data show significant correlations not only in the areas of high Aβ accumulation (e.g. precuneus) but also in some areas of medial temporal lobe (e.g. parahippocampal cortex), where Aβ accumulation is relatively low. We have demonstrated that GEPCI provides a new approach for the in vivo evaluation of AD-related tissue pathology in the preclinical and early symptomatic stages of AD. Since MRI is a widely available technology, the GEPCI surrogate markers of AD pathology have a potential for improving the quality of AD diagnostic, and the evaluation of new disease-modifying therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Rheological effects of drag-reducing polymers improve cerebral blood flow and oxygenation after traumatic brain injury in rats

PubMed Central

Kameneva, Marina V; Bragina, Olga A; Thomson, Susan; Statom, Gloria L; Lara, Devon A; Yang, Yirong; Nemoto, Edwin M

2016-01-01

Cerebral ischemia has been clearly demonstrated after traumatic brain injury (TBI); however, neuroprotective therapies have not focused on improvement of the cerebral microcirculation. Blood soluble drag-reducing polymers (DRP), prepared from high molecular weight polyethylene oxide, target impaired microvascular perfusion by altering the rheological properties of blood and, until our recent reports, has not been applied to the brain. We hypothesized that DRP improve cerebral microcirculation and oxygenation after TBI. DRP were studied in healthy and traumatized rat brains and compared to saline controls. Using in-vivo two-photon laser scanning microscopy over the parietal cortex, we showed that after TBI, nanomolar concentrations of intravascular DRP significantly enhanced microvascular perfusion and tissue oxygenation in peri-contusional areas, preserved blood–brain barrier integrity and protected neurons. The mechanisms of DRP effects were attributable to reduction of the near-vessel wall cell-free layer which increased near-wall blood flow velocity, microcirculatory volume flow, and number of erythrocytes entering capillaries, thereby reducing capillary stasis and tissue hypoxia as reflected by a reduction in NADH. Our results indicate that early reduction in CBF after TBI is mainly due to ischemia; however, metabolic depression of contused tissue could be also involved. PMID:28155574

Bioorthogonal chemical imaging of metabolic activities in live mammalian hippocampal tissues with stimulated Raman scattering

NASA Astrophysics Data System (ADS)

Hu, Fanghao; Lamprecht, Michael R.; Wei, Lu; Morrison, Barclay; Min, Wei

2016-12-01

Brain is an immensely complex system displaying dynamic and heterogeneous metabolic activities. Visualizing cellular metabolism of nucleic acids, proteins, and lipids in brain with chemical specificity has been a long-standing challenge. Recent development in metabolic labeling of small biomolecules allows the study of these metabolisms at the global level. However, these techniques generally require nonphysiological sample preparation for either destructive mass spectrometry imaging or secondary labeling with relatively bulky fluorescent labels. In this study, we have demonstrated bioorthogonal chemical imaging of DNA, RNA, protein and lipid metabolism in live rat brain hippocampal tissues by coupling stimulated Raman scattering microscopy with integrated deuterium and alkyne labeling. Heterogeneous metabolic incorporations for different molecular species and neurogenesis with newly-incorporated DNA were observed in the dentate gyrus of hippocampus at the single cell level. We further applied this platform to study metabolic responses to traumatic brain injury in hippocampal slice cultures, and observed marked upregulation of protein and lipid metabolism particularly in the hilus region of the hippocampus within days of mechanical injury. Thus, our method paves the way for the study of complex metabolic profiles in live brain tissue under both physiological and pathological conditions with single-cell resolution and minimal perturbation.

Segmentation of brain volume based on 3D region growing by integrating intensity and edge for image-guided surgery

NASA Astrophysics Data System (ADS)

Tsagaan, Baigalmaa; Abe, Keiichi; Goto, Masahiro; Yamamoto, Seiji; Terakawa, Susumu

2006-03-01

This paper presents a segmentation method of brain tissues from MR images, invented for our image-guided neurosurgery system under development. Our goal is to segment brain tissues for creating biomechanical model. The proposed segmentation method is based on 3-D region growing and outperforms conventional approaches by stepwise usage of intensity similarities between voxels in conjunction with edge information. Since the intensity and the edge information are complementary to each other in the region-based segmentation, we use them twice by performing a coarse-to-fine extraction. First, the edge information in an appropriate neighborhood of the voxel being considered is examined to constrain the region growing. The expanded region of the first extraction result is then used as the domain for the next processing. The intensity and the edge information of the current voxel only are utilized in the final extraction. Before segmentation, the intensity parameters of the brain tissues as well as partial volume effect are estimated by using expectation-maximization (EM) algorithm in order to provide an accurate data interpretation into the extraction. We tested the proposed method on T1-weighted MR images of brain and evaluated the segmentation effectiveness comparing the results with ground truths. Also, the generated meshes from the segmented brain volume by using mesh generating software are shown in this paper.

The Role of Multimodal Invasive Monitoring in Acute Traumatic Brain Injury.

PubMed

Lazaridis, Christos; Robertson, Claudia S

2016-10-01

This article reviews the role of modalities that directly monitor brain parenchyma in patients with severe traumatic brain injury. The physiology monitored involves compartmental and perfusion pressures, tissue oxygenation and metabolism, quantitative blood flow, pressure autoregulation, and electrophysiology. There are several proposed roles for this multimodality monitoring, such as to track, prevent, and treat the cascade of secondary brain injury; monitor the neurologically injured patient; integrate various data into a composite, patient-specific, and dynamic picture; apply protocolized, pathophysiology-driven intensive care; use as a prognostic marker; and understand pathophysiologic mechanisms involved in secondary brain injury to develop preventive and abortive therapies, and to inform future clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

Roles of elevated 20‑HETE in the breakdown of blood brain barrier and the severity of brain edema in experimental traumatic brain injury.

PubMed

Lu, Liyan; Wang, Mingliang; Yuan, Fang; Wei, Xiaoer; Li, Wenbin

2018-05-01

Breakdown of the blood brain barrier (BBB) is a secondary injury following traumatic brain injury (TBI) and can lead to the development of brain edema. However, the factors that contribute to the disruption of the BBB and increase the severity of brain edema in TBI remain to be elucidated. 20‑hydroxyeicosatetraenoic acid (20‑HETE) is a metabolite of arachidonic acid. The inhibition of 20‑HETEsynthesis by HET0016 has been suggested as a strategy to decrease brain edema. The present study aimed to investigate whether the elevated production of 20‑HETE in cerebral tissue may contribute to BBB breakdown and increase the severity of brain edema in rats with TBI. BBB permeability was quantified using dynamic contrast‑enhanced magnetic resonance imaging and brain edema was measured according to brain water content. Superoxide production in injured tissue was also assessed. Liquid chromatography‑mass spectrometry was used to evaluate 20‑HETE production in injured tissue. Western blot analysis was used to assess the expression of occludin, zonula occludens (ZO)‑1, matrix metalloproteinase (MMP)‑9, and proteins of the c‑Jun N‑terminal kinase (JNK) pathway. A total of 3, 24 and 72 h following the induction of TBI, 20‑HETE levels, BBB permeability and brain edema were identified to be increased, accompanied by an increase in superoxide production. Conversely, superoxide dismutase levels, in addition to the total antioxidative capability were decreased. In addition, the expression of MMP‑9 and proteins of the JNK pathway was upregulated, whereas the expression of occludin and ZO‑1 was observed to be suppressed. These results suggested that 20‑HETE may aggravate BBB disruption following TBI, via enhancing the expression of MMP‑9 and tight junction proteins. Furthermore, oxidative stress and the JNK signaling pathway may be involved in BBB dysregulation. In conclusion, the results of the present demonstrated that the production of 20‑HETE was increased in cerebral tissue following traumatic injury, thus suggesting that it may contribute to the compromise of BBB integrity and the development of brain edema.

Application of Texture Analysis to Study Small Vessel Disease and Blood-Brain Barrier Integrity.

PubMed

Valdés Hernández, Maria Del C; González-Castro, Victor; Chappell, Francesca M; Sakka, Eleni; Makin, Stephen; Armitage, Paul A; Nailon, William H; Wardlaw, Joanna M

2017-01-01

We evaluate the alternative use of texture analysis for evaluating the role of blood-brain barrier (BBB) in small vessel disease (SVD). We used brain magnetic resonance imaging from 204 stroke patients, acquired before and 20 min after intravenous gadolinium administration. We segmented tissues, white matter hyperintensities (WMH) and applied validated visual scores. We measured textural features in all tissues pre- and post-contrast and used ANCOVA to evaluate the effect of SVD indicators on the pre-/post-contrast change, Kruskal-Wallis for significance between patient groups and linear mixed models for pre-/post-contrast variations in cerebrospinal fluid (CSF) with Fazekas scores. Textural "homogeneity" increase in normal tissues with higher presence of SVD indicators was consistently more overt than in abnormal tissues. Textural "homogeneity" increased with age, basal ganglia perivascular spaces scores ( p  < 0.01) and SVD scores ( p  < 0.05) and was significantly higher in hypertensive patients ( p  < 0.002) and lacunar stroke ( p  = 0.04). Hypertension (74% patients), WMH load (median = 1.5 ± 1.6% of intracranial volume), and age (mean = 65.6 years, SD = 11.3) predicted the pre/post-contrast change in normal white matter, WMH, and index stroke lesion. CSF signal increased with increasing SVD post-contrast. A consistent general pattern of increasing textural "homogeneity" with increasing SVD and post-contrast change in CSF with increasing WMH suggest that texture analysis may be useful for the study of BBB integrity.

A miniaturized neuroprosthesis suitable for implantation into the brain

NASA Technical Reports Server (NTRS)

Mojarradi, Mohammad; Binkley, David; Blalock, Benjamin; Andersen, Richard; Ulshoefer, Norbert; Johnson, Travis; Del Castillo, Linda

2003-01-01

This paper presents current research on a miniaturized neuroprosthesis suitable for implantation into the brain. The prosthesis is a heterogeneous integration of a 100-element microelectromechanical system (MEMS) electrode array, front-end complementary metal-oxide-semiconductor (CMOS) integrated circuit for neural signal preamplification, filtering, multiplexing and analog-to-digital conversion, and a second CMOS integrated circuit for wireless transmission of neural data and conditioning of wireless power. The prosthesis is intended for applications where neural signals are processed and decoded to permit the control of artificial or paralyzed limbs. This research, if successful, will allow implantation of the electronics into the brain, or subcutaneously on the skull, and eliminate all external signal and power wiring. The neuroprosthetic system design has strict size and power constraints with each of the front-end preamplifier channels fitting within the 400 x 400-microm pitch of the 100-element MEMS electrode array and power dissipation resulting in less than a 1 degree C temperature rise for the surrounding brain tissue. We describe the measured performance of initial micropower low-noise CMOS preamplifiers for the neuroprosthetic.

Explaining brain size variation: from social to cultural brain.

PubMed

van Schaik, Carel P; Isler, Karin; Burkart, Judith M

2012-05-01

Although the social brain hypothesis has found near-universal acceptance as the best explanation for the evolution of extensive variation in brain size among mammals, it faces two problems. First, it cannot account for grade shifts, where species or complete lineages have a very different brain size than expected based on their social organization. Second, it cannot account for the observation that species with high socio-cognitive abilities also excel in general cognition. These problems may be related. For birds and mammals, we propose to integrate the social brain hypothesis into a broader framework we call cultural intelligence, which stresses the importance of the high costs of brain tissue, general behavioral flexibility and the role of social learning in acquiring cognitive skills. Copyright © 2012 Elsevier Ltd. All rights reserved.

Preservation of mitochondrial functional integrity in mitochondria isolated from small cryopreserved mouse brain areas.

PubMed

Valenti, Daniela; de Bari, Lidia; De Filippis, Bianca; Ricceri, Laura; Vacca, Rosa Anna

2014-01-01

Studies of mitochondrial bioenergetics in brain pathophysiology are often precluded by the need to isolate mitochondria immediately after tissue dissection from a large number of brain biopsies for comparative studies. Here we present a procedure of cryopreservation of small brain areas from which mitochondrial enriched fractions (crude mitochondria) with high oxidative phosphorylation efficiency can be isolated. Small mouse brain areas were frozen and stored in a solution containing glycerol as cryoprotectant. Crude mitochondria were isolated by differential centrifugation from both cryopreserved and freshly explanted brain samples and were compared with respect to their ability to generate membrane potential and produce ATP. Intactness of outer and inner mitochondrial membranes was verified by polarographic ascorbate and cytochrome c tests and spectrophotometric assay of citrate synthase activity. Preservation of structural integrity and oxidative phosphorylation efficiency was successfully obtained in crude mitochondria isolated from different areas of cryopreserved mouse brain samples. Long-term cryopreservation of small brain areas from which intact and phosphorylating mitochondria can be isolated for the study of mitochondrial bioenergetics will significantly expand the study of mitochondrial defects in neurological pathologies, allowing large comparative studies and favoring interlaboratory and interdisciplinary analyses. Copyright © 2013 Elsevier Inc. All rights reserved.

Good news–bad news: the Yin and Yang of immune privilege in the eye

PubMed Central

Forrester, John V.; Xu, Heping

2012-01-01

The eye and the brain are prototypical tissues manifesting immune privilege (IP) in which immune responses to foreign antigens, particularly alloantigens are suppressed, and even completely inhibited. Explanations for this phenomenon are numerous and mostly reflect our evolving understanding of the molecular and cellular processes underpinning immunological responses generally. IP is now viewed as a property of many tissues and the level of expression of IP varies not only with the tissue but with the nature of the foreign antigen and changes in the limited conditions under which privilege can operate as a mechanism of immunological tolerance. As a result, IP functions normally as a homeostatic mechanism preserving normal function in tissues, particularly those with highly specialized function and limited capacity for renewal such as the eye and brain. However, IP is relatively easily bypassed in the face of a sufficiently strong immunological response, and the privileged tissues may be at greater risk of collateral damage because its natural defenses are more easily breached than in a fully immunocompetent tissue which rapidly rejects foreign antigen and restores integrity. This two-edged sword cuts its swathe through the eye: under most circumstances, IP mechanisms such as blood–ocular barriers, intraocular immune modulators, induction of T regulatory cells, lack of lymphatics, and other properties maintain tissue integrity; however, when these are breached, various degrees of tissue damage occur from severe tissue destruction in retinal viral infections and other forms of uveoretinal inflammation, to less severe inflammatory responses in conditions such as macular degeneration. Conversely, ocular IP and tumor-related IP can combine to permit extensive tumor growth and increased risk of metastasis thus threatening the survival of the host. PMID:23230433

HZE particle radiation induces tissue-specific and p53-dependent mutagenesis in transgenic animals

NASA Technical Reports Server (NTRS)

Chang, P. Y.; Kanazawa, N.; Lutze-Mann, L.; Winegar, R.

2001-01-01

Transgenic animals, with the integrated target gene, provide a unique approach for measuring and characterizing mutations in any tissue of the animal. We are using the plasmid-based lacZ transgenic mice with different p53 genetic background to examine radiation-induced genetic damage resulting from exposure to heavy particle radiation. We measured lacZ mutation frequencies (MF) in the brain and spleen tissues at various times after exposing animals to an acute dose of 1 Gy of 1GeV/amu iron particles. MF in the spleen of p53+/+ animals increased up to 2.6-fold above spontaneous levels at 8 weeks post irradiation. In contrast, brain MF from the same animals increased 1.7-fold above controls in the same period. In the p53-/- animals, brain MF increased to 2.2-fold above spontaneous levels at 1 week after treatment, but returned to control levels thereafter. Radiation also induced alterations in the spectrum of mutants in both tissues, accompanied by changes in the frequency of mutants with deletions extending past the transgene into mouse genomic DNA. Our results indicate that the accumulation of transgene MF after radiation exposure is dependant on the tissue examined as well as the p53 genetic background of the animals.

The Expensive-Tissue Hypothesis in Vertebrates: Gut Microbiota Effect, a Review.

PubMed

Huang, Chun Hua; Yu, Xin; Liao, Wen Bo

2018-06-17

The gut microbiota is integral to an organism’s digestive structure and has been shown to play an important role in producing substrates for gluconeogenesis and energy production, vasodilator, and gut motility. Numerous studies have demonstrated that variation in diet types is associated with the abundance and diversity of the gut microbiota, a relationship that plays a significant role in nutrient absorption and affects gut size. The Expensive-Tissue Hypothesis states (ETH) that the metabolic requirement of relatively large brains is offset by a corresponding reduction of the other tissues, such as gut size. However, how the trade-off between gut size and brain size in vertebrates is associated with the gut microbiota through metabolic requirements still remains unexplored. Here, we review research relating to and discuss the potential influence of gut microbiota on the ETH.

Resonance Raman imaging for detecting and monitoring molecular pathological changes in human brain tumors related to Warburg effect

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; Zhu, Ke; Zhang, Chunyuan; Yang, Yang; Yu, Xinguang; Hu, Hailong; Cheng, Gangge; Wu, Binlin; Shi, Lingyan; Alfano, Robert R.

2018-02-01

The goal of the research is to determine the prognostic molecular pathological changes in components and composition, for human brain glioma gradings in comparison with normal tissues in three-dimensional Raman imaging profiles by visible Resonance Raman (VRR) imaging. VRR images from twenty-five specimens including three healthy tissues, one normal control, and twenty-one glioma tissues of grades II, II-III and III-IV with histology examination were measured and investigated using WITec300R confocal micro Raman imaging system with laser excitation of 532nm. Two-dimensional RR spectral mappings performed in 20μm x 20μm generated 400 images which integrated the intensity of the specific biochemical bonds as the third dimension. The three-dimension (3D) map demonstrated the spatial distributions of three selected sets of RR spectra of molecular biomarkers, and revealed significant differences in the spectra between normal and glioma tissues of different grades due to the composition changes in key molimageecules. These RR molecular spectral fingerprints have displayed: a clear enhancement of RR vibrational modes at 1129-1131cm-1 and 2934cm-1 which are supposed to be arising from lipoproteins; evident decreased RR vibrational modes at 1442cm-1 and 2854cm-1 which are from saturated fatty acids bonds in all-grades of glioma brain tissues compared with normal tissues; and the enhanced RR spectral modes of 1129 cm-1 and 2938cm-1 which suggest contribution from lactate. These findings may provide a novel proof for anaerobic glycolysis metabolic process in brain glioma cancer tissues that has been explained by Warburg effects.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shang, Yu; Yu, Guoqiang, E-mail: guoqiang.yu@uky.edu

Conventional semi-infinite analytical solutions of correlation diffusion equation may lead to errors when calculating blood flow index (BFI) from diffuse correlation spectroscopy (DCS) measurements in tissues with irregular geometries. Very recently, we created an algorithm integrating a Nth-order linear model of autocorrelation function with the Monte Carlo simulation of photon migrations in homogenous tissues with arbitrary geometries for extraction of BFI (i.e., αD{sub B}). The purpose of this study is to extend the capability of the Nth-order linear algorithm for extracting BFI in heterogeneous tissues with arbitrary geometries. The previous linear algorithm was modified to extract BFIs in different typesmore » of tissues simultaneously through utilizing DCS data at multiple source-detector separations. We compared the proposed linear algorithm with the semi-infinite homogenous solution in a computer model of adult head with heterogeneous tissue layers of scalp, skull, cerebrospinal fluid, and brain. To test the capability of the linear algorithm for extracting relative changes of cerebral blood flow (rCBF) in deep brain, we assigned ten levels of αD{sub B} in the brain layer with a step decrement of 10% while maintaining αD{sub B} values constant in other layers. Simulation results demonstrate the accuracy (errors < 3%) of high-order (N ≥ 5) linear algorithm in extracting BFIs in different tissue layers and rCBF in deep brain. By contrast, the semi-infinite homogenous solution resulted in substantial errors in rCBF (34.5% ≤ errors ≤ 60.2%) and BFIs in different layers. The Nth-order linear model simplifies data analysis, thus allowing for online data processing and displaying. Future study will test this linear algorithm in heterogeneous tissues with different levels of blood flow variations and noises.« less

Coating flexible probes with an ultra fast degrading polymer to aid in tissue insertion

PubMed Central

Wang, Shuwu; Singh, Sagar; Damodaran, Vinod B.; Kaplan, Hilton M.; Kohn, Joachim; Shreiber, David I.; Zahn, Jeffrey D.

2016-01-01

We report a fabrication process for coating neural probes with an ultrafast degrading polymer to create consistent and reproducible devices for neural tissue insertion. The rigid polymer coating acts as a probe insertion aid, but resorbs within hours post-implantation. Despite the feasibility for short term neural recordings from currently available neural prosthetic devices, most of these devices suffer from long term gliosis, which isolates the probes from adjacent neurons, increasing the recording impedance and stimulation threshold. The size and stiffness of implanted probes have been identified as critical factors that lead to this long term gliosis. Smaller, more flexible probes that match the mechanical properties of brain tissue could allow better long term integration by limiting the mechanical disruption of the surrounding tissue during and after probe insertion, while being flexible enough to deform with the tissue during brain movement. However, these small flexible probes inherently lack the mechanical strength to penetrate the brain on their own. In this work, we have developed a micromolding method for coating a non-functional miniaturized SU-8 probe with an ultrafast degrading tyrosine-derived polycarbonate (E5005(2K)). Coated, non-functionalized probes of varying dimensions were reproducibly fabricated with high yields. The polymer erosion/degradation profiles of the probes were characterized in vitro. The probes were also mechanically characterized in ex vivo brain tissue models by measuring buckling and insertion forces during probe insertion. The results demonstrate the ability to produce polymer coated probes of consistent quality for future in vivo use, for example to study the effects of different design parameters that may affect tissue response during long term chronic intra-cortical microelectrode neural recordings. PMID:25681971

Coating flexible probes with an ultra fast degrading polymer to aid in tissue insertion.

PubMed

Lo, Meng-chen; Wang, Shuwu; Singh, Sagar; Damodaran, Vinod B; Kaplan, Hilton M; Kohn, Joachim; Shreiber, David I; Zahn, Jeffrey D

2015-04-01

We report a fabrication process for coating neural probes with an ultrafast degrading polymer to create consistent and reproducible devices for neural tissue insertion. The rigid polymer coating acts as a probe insertion aid, but resorbs within hours post-implantation. Despite the feasibility for short term neural recordings from currently available neural prosthetic devices, most of these devices suffer from long term gliosis, which isolates the probes from adjacent neurons, increasing the recording impedance and stimulation threshold. The size and stiffness of implanted probes have been identified as critical factors that lead to this long term gliosis. Smaller, more flexible probes that match the mechanical properties of brain tissue could allow better long term integration by limiting the mechanical disruption of the surrounding tissue during and after probe insertion, while being flexible enough to deform with the tissue during brain movement. However, these small flexible probes inherently lack the mechanical strength to penetrate the brain on their own. In this work, we have developed a micromolding method for coating a non-functional miniaturized SU-8 probe with an ultrafast degrading tyrosine-derived polycarbonate (E5005(2K)). Coated, non-functionalized probes of varying dimensions were reproducibly fabricated with high yields. The polymer erosion/degradation profiles of the probes were characterized in vitro. The probes were also mechanically characterized in ex vivo brain tissue models by measuring buckling and insertion forces during probe insertion. The results demonstrate the ability to produce polymer coated probes of consistent quality for future in vivo use, for example to study the effects of different design parameters that may affect tissue response during long term chronic intra-cortical microelectrode neural recordings.

Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities.

PubMed

McDonald, Robert J; McDonald, Jennifer S; Kallmes, David F; Jentoft, Mark E; Paolini, Michael A; Murray, David L; Williamson, Eric E; Eckel, Laurence J

2017-11-01

Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate <45 mL/min/1.73 m 2 ) and hepatobiliary dysfunction at MR examination. Gadolinium deposition in the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial abnormalities that might affect the permeability of the blood-brain barrier. These findings challenge current understanding of the biodistribution of these contrast agents and their safety. © RSNA, 2017.

Comprehensive approach to image-guided surgery

NASA Astrophysics Data System (ADS)

Peters, Terence M.; Comeau, Roch M.; Kasrai, Reza; St. Jean, Philippe; Clonda, Diego; Sinasac, M.; Audette, Michel A.; Fenster, Aaron

1998-06-01

Image-guided surgery has evolved over the past 15 years from stereotactic planning, where the surgeon planned approaches to intracranial targets on the basis of 2D images presented on a simple workstation, to the use of sophisticated multi- modality 3D image integration in the operating room, with guidance being provided by mechanically, optically or electro-magnetically tracked probes or microscopes. In addition, sophisticated procedures such as thalamotomies and pallidotomies to relieve the symptoms of Parkinson's disease, are performed with the aid of volumetric atlases integrated with the 3D image data. Operations that are performed stereotactically, that is to say via a small burr- hole in the skull, are able to assume that the information contained in the pre-operative imaging study, accurately represents the brain morphology during the surgical procedure. On the other hand, preforming a procedure via an open craniotomy presents a problem. Not only does tissue shift when the operation begins, even the act of opening the skull can cause significant shift of the brain tissue due to the relief of intra-cranial pressure, or the effect of drugs. Means of tracking and correcting such shifts from an important part of the work in the field of image-guided surgery today. One approach has ben through the development of intra-operative MRI imaging systems. We describe an alternative approach which integrates intra-operative ultrasound with pre-operative MRI to track such changes in tissue morphology.

The tissue-type plasminogen activator–plasminogen activator inhibitor 1 complex promotes neurovascular injury in brain trauma: evidence from mice and humans

PubMed Central

Sashindranath, Maithili; Sales, Eunice; Daglas, Maria; Freeman, Roxann; Samson, Andre L.; Cops, Elisa J.; Beckham, Simone; Galle, Adam; McLean, Catriona; Morganti-Kossmann, Cristina; Rosenfeld, Jeffrey V.; Madani, Rime; Vassalli, Jean-Dominique; Su, Enming J.; Lawrence, Daniel A.

2012-01-01

The neurovascular unit provides a dynamic interface between the circulation and central nervous system. Disruption of neurovascular integrity occurs in numerous brain pathologies including neurotrauma and ischaemic stroke. Tissue plasminogen activator is a serine protease that converts plasminogen to plasmin, a protease that dissolves blood clots. Besides its role in fibrinolysis, tissue plasminogen activator is abundantly expressed in the brain where it mediates extracellular proteolysis. However, proteolytically active tissue plasminogen activator also promotes neurovascular disruption after ischaemic stroke; the molecular mechanisms of this process are still unclear. Tissue plasminogen activator is naturally inhibited by serine protease inhibitors (serpins): plasminogen activator inhibitor-1, neuroserpin or protease nexin-1 that results in the formation of serpin:protease complexes. Proteases and serpin:protease complexes are cleared through high-affinity binding to low-density lipoprotein receptors, but their binding to these receptors can also transmit extracellular signals across the plasma membrane. The matrix metalloproteinases are the second major proteolytic system in the mammalian brain, and like tissue plasminogen activators are pivotal to neurological function but can also degrade structures of the neurovascular unit after injury. Herein, we show that tissue plasminogen activator potentiates neurovascular damage in a dose-dependent manner in a mouse model of neurotrauma. Surprisingly, inhibition of activity following administration of plasminogen activator inhibitor-1 significantly increased cerebrovascular permeability. This led to our finding that formation of complexes between tissue plasminogen activator and plasminogen activator inhibitor-1 in the brain parenchyma facilitates post-traumatic cerebrovascular damage. We demonstrate that following trauma, the complex binds to low-density lipoprotein receptors, triggering the induction of matrix metalloproteinase-3. Accordingly, pharmacological inhibition of matrix metalloproteinase-3 attenuates neurovascular permeability and improves neurological function in injured mice. Our results are clinically relevant, because concentrations of tissue plasminogen activator: plasminogen activator inhibitor-1 complex and matrix metalloproteinase-3 are significantly elevated in cerebrospinal fluid of trauma patients and correlate with neurological outcome. In a separate study, we found that matrix metalloproteinase-3 and albumin, a marker of cerebrovascular damage, were significantly increased in brain tissue of patients with neurotrauma. Perturbation of neurovascular homeostasis causing oedema, inflammation and cell death is an important cause of acute and long-term neurological dysfunction after trauma. A role for the tissue plasminogen activator–matrix metalloproteinase axis in promoting neurovascular disruption after neurotrauma has not been described thus far. Targeting tissue plasminogen activator: plasminogen activator inhibitor-1 complex signalling or downstream matrix metalloproteinase-3 induction may provide viable therapeutic strategies to reduce cerebrovascular permeability after neurotrauma. PMID:22822039

Hemodynamic and morphologic responses in mouse brain during acute head injury imaged by multispectral structured illumination

NASA Astrophysics Data System (ADS)

Volkov, Boris; Mathews, Marlon S.; Abookasis, David

2015-03-01

Multispectral imaging has received significant attention over the last decade as it integrates spectroscopy, imaging, tomography analysis concurrently to acquire both spatial and spectral information from biological tissue. In the present study, a multispectral setup based on projection of structured illumination at several near-infrared wavelengths and at different spatial frequencies is applied to quantitatively assess brain function before, during, and after the onset of traumatic brain injury in an intact mouse brain (n=5). For the production of head injury, we used the weight drop method where weight of a cylindrical metallic rod falling along a metal tube strikes the mouse's head. Structured light was projected onto the scalp surface and diffuse reflected light was recorded by a CCD camera positioned perpendicular to the mouse head. Following data analysis, we were able to concurrently show a series of hemodynamic and morphologic changes over time including higher deoxyhemoglobin, reduction in oxygen saturation, cell swelling, etc., in comparison with baseline measurements. Overall, results demonstrates the capability of multispectral imaging based structured illumination to detect and map of brain tissue optical and physiological properties following brain injury in a simple noninvasive and noncontact manner.

Proposals for best-quality immunohistochemical staining of paraffin-embedded brain tissue slides in forensics.

PubMed

Trautz, Florian; Dreßler, Jan; Stassart, Ruth; Müller, Wolf; Ondruschka, Benjamin

2018-01-03

Immunohistochemistry (IHC) has become an integral part in forensic histopathology over the last decades. However, the underlying methods for IHC vary greatly depending on the institution, creating a lack of comparability. The aim of this study was to assess the optimal approach for different technical aspects of IHC, in order to improve and standardize this procedure. Therefore, qualitative results from manual and automatic IHC staining of brain samples were compared, as well as potential differences in suitability of common IHC glass slides. Further, possibilities of image digitalization and connected issues were investigated. In our study, automatic staining showed more consistent staining results, compared to manual staining procedures. Digitalization and digital post-processing facilitated direct analysis and analysis for reproducibility considerably. No differences were found for different commercially available microscopic glass slides regarding suitability of IHC brain researches, but a certain rate of tissue loss should be expected during the staining process.

Neuromodulation, agency and autonomy.

PubMed

Glannon, Walter

2014-01-01

Neuromodulation consists in altering brain activity to restore mental and physical functions in individuals with neuropsychiatric disorders and brain and spinal cord injuries. This can be achieved by delivering electrical stimulation that excites or inhibits neural tissue, by using electrical signals in the brain to move computer cursors or robotic arms, or by displaying brain activity to subjects who regulate that activity by their own responses to it. As enabling prostheses, deep-brain stimulation and brain-computer interfaces (BCIs) are forms of extended embodiment that become integrated into the individual's conception of himself as an autonomous agent. In BCIs and neurofeedback, the success or failure of the techniques depends on the interaction between the learner and the trainer. The restoration of agency and autonomy through neuromodulation thus involves neurophysiological, psychological and social factors.

Tau depletion prevents progressive blood-brain barrier damage in a mouse model of tauopathy.

PubMed

Blair, Laura J; Frauen, Haley D; Zhang, Bo; Nordhues, Bryce A; Bijan, Sara; Lin, Yen-Chi; Zamudio, Frank; Hernandez, Lidice D; Sabbagh, Jonathan J; Selenica, Maj-Linda B; Dickey, Chad A

2015-01-31

The blood-brain barrier (BBB) is damaged in tauopathies, including progressive supranuclear palsy (PSP) and Alzheimer's disease (AD), which is thought to contribute to pathogenesis later in the disease course. In AD, BBB dysfunction has been associated with amyloid beta (Aß) pathology, but the role of tau in this process is not well characterized. Since increased BBB permeability is found in tauopathies without Aß pathology, like PSP, we suspected that tau accumulation alone could not only be sufficient, but even more important than Aß for BBB damage. Longitudinal evaluation of brain tissue from the tetracycline-regulatable rTg4510 tau transgenic mouse model showed progressive IgG, T cell and red blood cell infiltration. The Evans blue (EB) dye that is excluded from the brain when the BBB is intact also permeated the brains of rTg4510 mice following peripheral administration, indicative of a bonafide BBB defect, but this was only evident later in life. Thus, despite the marked brain atrophy and inflammation that occurs earlier in this model, BBB integrity is maintained. Interestingly, BBB dysfunction emerged at the same time that perivascular tau emerged around major hippocampal blood vessels. However, when tau expression was suppressed using doxycycline, BBB integrity was preserved, suggesting that the BBB can be stabilized in a tauopathic brain by reducing tau levels. For the first time, these data demonstrate that tau alone can initiate breakdown of the BBB, but the BBB is remarkably resilient, maintaining its integrity in the face of marked brain atrophy, neuroinflammation and toxic tau accumulation. Moreover, the BBB can recover integrity when tau levels are reduced. Thus, late stage interventions targeting tau may slow the vascular contributions to cognitive impairment and dementia that occur in tauopathies.

An Integrative Platform for Three-dimensional Quantitative Analysis of Spatially Heterogeneous Metastasis Landscapes

NASA Astrophysics Data System (ADS)

Guldner, Ian H.; Yang, Lin; Cowdrick, Kyle R.; Wang, Qingfei; Alvarez Barrios, Wendy V.; Zellmer, Victoria R.; Zhang, Yizhe; Host, Misha; Liu, Fang; Chen, Danny Z.; Zhang, Siyuan

2016-04-01

Metastatic microenvironments are spatially and compositionally heterogeneous. This seemingly stochastic heterogeneity provides researchers great challenges in elucidating factors that determine metastatic outgrowth. Herein, we develop and implement an integrative platform that will enable researchers to obtain novel insights from intricate metastatic landscapes. Our two-segment platform begins with whole tissue clearing, staining, and imaging to globally delineate metastatic landscape heterogeneity with spatial and molecular resolution. The second segment of our platform applies our custom-developed SMART 3D (Spatial filtering-based background removal and Multi-chAnnel forest classifiers-based 3D ReconsTruction), a multi-faceted image analysis pipeline, permitting quantitative interrogation of functional implications of heterogeneous metastatic landscape constituents, from subcellular features to multicellular structures, within our large three-dimensional (3D) image datasets. Coupling whole tissue imaging of brain metastasis animal models with SMART 3D, we demonstrate the capability of our integrative pipeline to reveal and quantify volumetric and spatial aspects of brain metastasis landscapes, including diverse tumor morphology, heterogeneous proliferative indices, metastasis-associated astrogliosis, and vasculature spatial distribution. Collectively, our study demonstrates the utility of our novel integrative platform to reveal and quantify the global spatial and volumetric characteristics of the 3D metastatic landscape with unparalleled accuracy, opening new opportunities for unbiased investigation of novel biological phenomena in situ.

Advanced biomaterial strategies to transplant preformed micro-tissue engineered neural networks into the brain

NASA Astrophysics Data System (ADS)

Harris, J. P.; Struzyna, L. A.; Murphy, P. L.; Adewole, D. O.; Kuo, E.; Cullen, D. K.

2016-02-01

Objective. Connectome disruption is a hallmark of many neurological diseases and trauma with no current strategies to restore lost long-distance axonal pathways in the brain. We are creating transplantable micro-tissue engineered neural networks (micro-TENNs), which are preformed constructs consisting of embedded neurons and long axonal tracts to integrate with the nervous system to physically reconstitute lost axonal pathways. Approach. We advanced micro-tissue engineering techniques to generate micro-TENNs consisting of discrete populations of mature primary cerebral cortical neurons spanned by long axonal fascicles encased in miniature hydrogel micro-columns. Further, we improved the biomaterial encasement scheme by adding a thin layer of low viscosity carboxymethylcellulose (CMC) to enable needle-less insertion and rapid softening for mechanical similarity with brain tissue. Main results. The engineered architecture of cortical micro-TENNs facilitated robust neuronal viability and axonal cytoarchitecture to at least 22 days in vitro. Micro-TENNs displayed discrete neuronal populations spanned by long axonal fasciculation throughout the core, thus mimicking the general systems-level anatomy of gray matter—white matter in the brain. Additionally, micro-columns with thin CMC-coating upon mild dehydration were able to withstand a force of 893 ± 457 mN before buckling, whereas a solid agarose cylinder of similar dimensions was predicted to withstand less than 150 μN of force. This thin CMC coating increased the stiffness by three orders of magnitude, enabling needle-less insertion into brain while significantly reducing the footprint of previous needle-based delivery methods to minimize insertion trauma. Significance. Our novel micro-TENNs are the first strategy designed for minimally invasive implantation to facilitate nervous system repair by simultaneously providing neuronal replacement and physical reconstruction of long-distance axon pathways in the brain. The micro-TENN approach may offer the ability to treat several disorders that disrupt the connectome, including Parkinson’s disease, traumatic brain injury, stroke, and brain tumor excision.

Advanced biomaterial strategies to transplant preformed micro-tissue engineered neural networks into the brain

PubMed Central

Harris, J P; Struzyna, L A; Murphy, P L; Adewole, D O; Kuo, E; Cullen, D K

2017-01-01

Objective Connectome disruption is a hallmark of many neurological diseases and trauma with no current strategies to restore lost long-distance axonal pathways in the brain. We are creating transplantable micro-tissue engineered neural networks (micro-TENNs), which are preformed constructs consisting of embedded neurons and long axonal tracts to integrate with the nervous system to physically reconstitute lost axonal pathways. Approach We advanced micro-tissue engineering techniques to generate micro-TENNs consisting of discrete populations of mature primary cerebral cortical neurons spanned by long axonal fascicles encased in miniature hydrogel micro-columns. Further, we improved the biomaterial encasement scheme by adding a thin layer of low viscosity carboxymethylcellulose (CMC) to enable needle-less insertion and rapid softening for mechanical similarity with brain tissue. Main results The engineered architecture of cortical micro-TENNs facilitated robust neuronal viability and axonal cytoarchitecture to at least 22 days in vitro. Micro-TENNs displayed discrete neuronal populations spanned by long axonal fasciculation throughout the core, thus mimicking the general systems-level anatomy of gray matter—white matter in the brain. Additionally, micro columns with thin CMC-coating upon mild dehydration were able to withstand a force of 893 ± 457 mN before buckling, whereas a solid agarose cylinder of similar dimensions was predicted to withstand less than 150 μN of force. This thin CMC coating increased the stiffness by three orders of magnitude, enabling needle-less insertion into brain while significantly reducing the footprint of previous needle-based delivery methods to minimize insertion trauma. Significance Our novel micro-TENNs are the first strategy designed for minimally invasive implantation to facilitate nervous system repair by simultaneously providing neuronal replacement and physical reconstruction of long-distance axon pathways in the brain. The micro-TENN approach may offer the ability to treat several disorders that disrupt the connectome, including Parkinson’s disease, traumatic brain injury, stroke, and brain tumor excision PMID:26760138

An evaluation of a reagentless method for the determination of total mercury in aquatic life

USGS Publications Warehouse

Haynes, Sekeenia; Gragg, Richard D.; Johnson, Elijah; Robinson, Larry; Orazio, Carl E.

2006-01-01

Multiple treatment (i.e., drying, chemical digestion, and oxidation) steps are often required during preparation of biological matrices for quantitative analysis of mercury; these multiple steps could potentially lead to systematic errors and poor recovery of the analyte. In this study, the Direct Mercury Analyzer (Milestone Inc., Monroe, CT) was utilized to measure total mercury in fish tissue by integrating steps of drying, sample combustion and gold sequestration with successive identification using atomic absorption spectrometry. We also evaluated the differences between the mercury concentrations found in samples that were homogenized and samples with no preparation. These results were confirmed with cold vapor atomic absorbance and fluorescence spectrometric methods of analysis. Finally, total mercury in wild captured largemouth bass (n = 20) were assessed using the Direct Mercury Analyzer to examine internal variability between mercury concentrations in muscle, liver and brain organs. Direct analysis of total mercury measured in muscle tissue was strongly correlated with muscle tissue that was homogenized before analysis (r = 0.81, p < 0.0001). Additionally, results using this integrated method compared favorably (p < 0.05) with conventional cold vapor spectrometry with atomic absorbance and fluorescence detection methods. Mercury concentrations in brain were significantly lower than concentrations in muscle (p < 0.001) and liver (p < 0.05) tissues. This integrated method can measure a wide range of mercury concentrations (0-500 ??g) using small sample sizes. Total mercury measurements in this study are comparative to the methods (cold vapor) commonly used for total mercury analysis and are devoid of laborious sample preparation and expensive hazardous waste. ?? Springer 2006.

Electrical bioimpedance enabling prompt intervention in traumatic brain injury

NASA Astrophysics Data System (ADS)

Seoane, Fernando; Atefi, S. Reza

2017-05-01

Electrical Bioimpedance (EBI) is a well spread technology used in clinical practice across the world. Advancements in Textile material technology with conductive textile fabrics and textile-electronics integration have allowed exploring potential applications for Wearable Measurement Sensors and Systems exploiting. The sensing principle of electrical bioimpedance is based on the intrinsic passive dielectric properties of biological tissue. Using a pair of electrodes, tissue is electrically stimulated and the electrical response can be sensed with another pair of surface electrodes. EBI spectroscopy application for cerebral monitoring of neurological conditions such as stroke and perinatal asphyxia in newborns have been justified using animal studies and computational simulations. Such studies have shown proof of principle that neurological pathologies indeed modify the dielectric composition of the brain that is detectable via EBI. Similar to stroke, Traumatic Brain Injury (TBI) also affects the dielectric properties of brain tissue that can be detected via EBI measurements. Considering the portable and noninvasive characteristics of EBI it is potentially useful for prehospital triage of TBI patients where. In the battlefield blast induced Traumatic Brain Injuries are very common. Brain damage must be assessed promptly to have a chance to prevent severe damage or eventually death. The relatively low-complexity of the sensing hardware required for EBI sensing and the already proven compatibility with textile electrodes suggest the EBI technology is indeed a candidate for developing a handheld device equipped with a sensorized textile cap to produce an examination in minutes for enabling medically-guided prompt intervention.

A systematic survey of lipids across mouse tissues

PubMed Central

Jain, Mohit; Ngoy, Soeun; Sheth, Sunil A.; Swanson, Raymond A.; Rhee, Eugene P.; Liao, Ronglih; Clish, Clary B.; Mootha, Vamsi K.

2014-01-01

Lipids are a diverse collection of macromolecules essential for normal physiology, but the tissue distribution and function for many individual lipid species remain unclear. Here, we report a mass spectrometry survey of lipid abundance across 18 mouse tissues, detecting ∼1,000 mass spectrometry features, of which we identify 179 lipids from the glycerolipids, glycerophospholipids, lysophospholipids, acylcarnitines, sphingolipids, and cholesteryl ester classes. Our data reveal tissue-specific organization of lipids and can be used to generate testable hypotheses. For example, our data indicate that circulating triglycerides positively and negatively associated with future diabetes in humans are enriched in mouse adipose tissue and liver, respectively, raising hypotheses regarding the tissue origins of these diabetes-associated lipids. We also integrate our tissue lipid data with gene expression profiles to predict a number of substrates of lipid-metabolizing enzymes, highlighting choline phosphotransferases and sterol O-acyltransferases. Finally, we identify several tissue-specific lipids not present in plasma under normal conditions that may be of interest as biomarkers of tissue injury, and we show that two of these lipids are released into blood following ischemic brain injury in mice. This resource complements existing compendia of tissue gene expression and may be useful for integrative physiology and lipid biology. PMID:24518676

Magnetic Resonance Elastography of the Brain using Multi-Shot Spiral Readouts with Self-Navigated Motion Correction

PubMed Central

Johnson, Curtis L.; McGarry, Matthew D. J.; Van Houten, Elijah E. W.; Weaver, John B.; Paulsen, Keith D.; Sutton, Bradley P.; Georgiadis, John G.

2012-01-01

MRE has been introduced in clinical practice as a possible surrogate for mechanical palpation, but its application to study the human brain in vivo has been limited by low spatial resolution and the complexity of the inverse problem associated with biomechanical property estimation. Here, we report significant improvements in brain MRE data acquisition by reporting images with high spatial resolution and signal-to-noise ratio as quantified by octahedral shear strain metrics. Specifically, we have developed a sequence for brain MRE based on multi-shot, variable-density spiral imaging and three-dimensional displacement acquisition, and implemented a correction scheme for any resulting phase errors. A Rayleigh damped model of brain tissue mechanics was adopted to represent the parenchyma, and was integrated via a finite element-based iterative inversion algorithm. A multi-resolution phantom study demonstrates the need for obtaining high-resolution MRE data when estimating focal mechanical properties. Measurements on three healthy volunteers demonstrate satisfactory resolution of grey and white matter, and mechanical heterogeneities correspond well with white matter histoarchitecture. Together, these advances enable MRE scans that result in high-fidelity, spatially-resolved estimates of in vivo brain tissue mechanical properties, improving upon lower resolution MRE brain studies which only report volume averaged stiffness values. PMID:23001771

Diffuse Optical Tomography for Brain Imaging: Theory

NASA Astrophysics Data System (ADS)

Yuan, Zhen; Jiang, Huabei

Diffuse optical tomography (DOT) is a noninvasive, nonionizing, and inexpensive imaging technique that uses near-infrared light to probe tissue optical properties. Regional variations in oxy- and deoxy-hemoglobin concentrations as well as blood flow and oxygen consumption can be imaged by monitoring spatiotemporal variations in the absorption spectra. For brain imaging, this provides DOT unique abilities to directly measure the hemodynamic, metabolic, and neuronal responses to cells (neurons), and tissue and organ activations with high temporal resolution and good tissue penetration. DOT can be used as a stand-alone modality or can be integrated with other imaging modalities such as fMRI/MRI, PET/CT, and EEG/MEG in studying neurophysiology and pathology. This book chapter serves as an introduction to the basic theory and principles of DOT for neuroimaging. It covers the major aspects of advances in neural optical imaging including mathematics, physics, chemistry, reconstruction algorithm, instrumentation, image-guided spectroscopy, neurovascular and neurometabolic coupling, and clinical applications.

Biological annotation of genetic loci associated with intelligence in a meta-analysis of 87,740 individuals.

PubMed

Coleman, Jonathan R I; Bryois, Julien; Gaspar, Héléna A; Jansen, Philip R; Savage, Jeanne E; Skene, Nathan; Plomin, Robert; Muñoz-Manchado, Ana B; Linnarsson, Sten; Crawford, Greg; Hjerling-Leffler, Jens; Sullivan, Patrick F; Posthuma, Danielle; Breen, Gerome

2018-03-08

Variance in IQ is associated with a wide range of health outcomes, and 1% of the population are affected by intellectual disability. Despite a century of research, the fundamental neural underpinnings of intelligence remain unclear. We integrate results from genome-wide association studies (GWAS) of intelligence with brain tissue and single cell gene expression data to identify tissues and cell types associated with intelligence. GWAS data for IQ (N = 78,308) were meta-analyzed with a study comparing 1247 individuals with mean IQ ~170 to 8185 controls. Genes associated with intelligence implicate pyramidal neurons of the somatosensory cortex and CA1 region of the hippocampus, and midbrain embryonic GABAergic neurons. Tissue-specific analyses find the most significant enrichment for frontal cortex brain expressed genes. These results suggest specific neuronal cell types and genes may be involved in intelligence and provide new hypotheses for neuroscience experiments using model systems.

Elastic and viscoelastic mechanical properties of brain tissues on the implanting trajectory of sub-thalamic nucleus stimulation.

PubMed

Li, Yan; Deng, Jianxin; Zhou, Jun; Li, Xueen

2016-11-01

Corresponding to pre-puncture and post-puncture insertion, elastic and viscoelastic mechanical properties of brain tissues on the implanting trajectory of sub-thalamic nucleus stimulation are investigated, respectively. Elastic mechanical properties in pre-puncture are investigated through pre-puncture needle insertion experiments using whole porcine brains. A linear polynomial and a second order polynomial are fitted to the average insertion force in pre-puncture. The Young's modulus in pre-puncture is calculated from the slope of the two fittings. Viscoelastic mechanical properties of brain tissues in post-puncture insertion are investigated through indentation stress relaxation tests for six interested regions along a planned trajectory. A linear viscoelastic model with a Prony series approximation is fitted to the average load trace of each region using Boltzmann hereditary integral. Shear relaxation moduli of each region are calculated using the parameters of the Prony series approximation. The results show that, in pre-puncture insertion, needle force almost increases linearly with needle displacement. Both fitting lines can perfectly fit the average insertion force. The Young's moduli calculated from the slope of the two fittings are worthy of trust to model linearly or nonlinearly instantaneous elastic responses of brain tissues, respectively. In post-puncture insertion, both region and time significantly affect the viscoelastic behaviors. Six tested regions can be classified into three categories in stiffness. Shear relaxation moduli decay dramatically in short time scales but equilibrium is never truly achieved. The regional and temporal viscoelastic mechanical properties in post-puncture insertion are valuable for guiding probe insertion into each region on the implanting trajectory.

Optimized heterologous transfection of viable adult organotypic brain slices using an enhanced gene gun

PubMed Central

2013-01-01

Background Organotypic brain slices (OTBS) are an excellent experimental compromise between the facility of working with cell cultures and the biological relevance of using animal models where anatomical, morphological, and cellular function of specific brain regions can be maintained. The biological characteristics of OTBS can subsequently be examined under well-defined conditions. They do, however, have a number of limitations; most brain slices are derived from neonatal animals, as it is difficult to properly prepare and maintain adult OTBS. There are ample problems with tissue integrity as OTBS are delicate and frequently become damaged during the preparative stages. Notwithstanding these obstacles, the introduced exogenous proteins into both neuronal cells, and cells imbedded within tissues, have been consistently difficult to achieve. Results Following the ex vivo extraction of adult mouse brains, mounted inside a medium-agarose matrix, we have exploited a precise slicing procedure using a custom built vibroslicer. To transfect these slices we used an improved biolistic transfection method using a custom made low-pressure barrel and novel DNA-coated nanoparticles (40 nm), which are drastically smaller than traditional microparticles. These nanoparticles also minimize tissue damage as seen by a significant reduction in lactate dehydrogenase activity as well as propidium iodide (PI) and dUTP labelling compared to larger traditional gold particles used on these OTBS. Furthermore, following EYFP exogene delivery by gene gun, the 40 nm treated OTBS displayed a significantly larger number of viable NeuN and EYFP positive cells. These OTBS expressed the exogenous proteins for many weeks. Conclusions Our described methodology of producing OTBS, which results in better reproducibility with less tissue damage, permits the exploitation of mature fully formed adult brains for advanced neurobiological studies. The novel 40 nm particles are ideal for the viable biolistic transfection of OTBS by reducing tissue stress while maintaining long term exogene expression. PMID:24354851

SU-D-BRB-04: Plan Quality Comparison of Intracranial Stereotactic Radiosurgery (SRS) for Gamma Knife and VMAT Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keeling, V; Algan, O; Ahmad, S

2015-06-15

Purpose: To compare treatment plan quality of intracranial stereotactic radiosurgery (SRS) for VMAT (RapidArc) and Gamma Knife (GK) systems. Methods: Ten patients with 24 tumors (seven with 1–2 and three with 4–6 lesions), previously treated with GK 4C (prescription doses ranging from 14–23 Gy) were re-planned for RapidArc. Identical contour sets were kept on MRI images for both plans with tissues assigned a CT number of zero. RapidArc plans were performed using 6 MV flattening-filter-free (FFF) beams with dose rate of 1400 MU/minute using two to eight arcs with the following combinations: 2 full coplanar arcs and the rest non-coplanarmore » half arcs. Beam selection was based on target depth. Areas that penetrated more than 10 cm of tissue were avoided by creating smaller arcs or using avoidance sectors in optimization. Plans were optimized with jaw tracking and a high weighting to the normal-brain-tissue and Normal-Tissue-Objective without compromising PTV coverage. Plans were calculated on a 1 mm grid size using AAA algorithm and then normalized so that 99% of each target volume received the prescription dose. Plan quality was assessed by target coverage using Paddick Conformity Index (PCI), sparing of normal-brain-tissue through analysis of V4, V8, and V12 Gy, and integral dose. Results: In all cases critical structure dose criteria were met. RapidArc had a higher PCI than GK plans for 23 out of 24 lesions. The average PCI was 0.76±0.21 for RapidArc and 0.46±0.20 for GK plans (p≤0.001), respectively. Integral dose and normal-brain-tissue doses for all criteria were lower for RapidArc in nearly all patients. The average ratio of GK to RapidArc plans was 1.28±0.27 (p=0.018), 1.31±0.25 (p=0.017), 1.81±0.43 (p=0.005), and 1.50±0.61 (p=0.006) for V4, V8, and V12 Gy, and integral dose, respectively. Conclusion: VMAT was capable of producing higher quality treatment plans than GK when using optimal beam geometries and proper optimization techniques.« less

Mesenchymal Stem Cells Regulate Blood Brain Barrier Integrity in Traumatic Brain Injury Through Production of the Soluble Factor TIMP3

PubMed Central

Menge, Tyler; Zhao, Yuhai; Zhao, Jing; Wataha, Kathryn; Geber, Michael; Zhang, Jianhu; Letourneau, Phillip; Redell, John; Shen, Li; Wang, Jing; Peng, Zhalong; Xue, Hasen; Kozar, Rosemary; Cox, Charles S.; Khakoo, Aarif Y.; Holcomb, John B.; Dash, Pramod K.; Pati, Shibani

2013-01-01

Mesenchymal stem cells (MCSs) have been shown to have therapeutic potential in multiple disease states associated with vascular instability including traumatic brain injury (TBI). In the present study, Tissue Inhibitor of Matrix Metalloproteinase-3 (TIMP3) is identified as the soluble factor produced by MSCs that can recapitulate the beneficial effects of MSCs on endothelial function and blood brain barrier (BBB) compromise in TBI. Attenuation of TIMP3 expression in MSCs completely abrogates the effect of MSCs on BBB permeability and stability, while intravenous administration of rTIMP3 alone can inhibit BBB permeability in TBI. Our results demonstrate that MSCs increase circulating levels of soluble TIMP3, which inhibits VEGF-A induced breakdown of endothelial AJs in vitro and in vivo. These findings elucidate a clear molecular mechanism for the effects of MSCs on the BBB in TBI, and directly demonstrate a role for TIMP3 in regulation of BBB integrity. PMID:23175708

Integration of transcriptomic and cytoarchitectonic data implicates a role for MAOA and TAC1 in the limbic-cortical network.

PubMed

Bludau, Sebastian; Mühleisen, Thomas W; Eickhoff, Simon B; Hawrylycz, Michael J; Cichon, Sven; Amunts, Katrin

2018-06-01

Decoding the chain from genes to cognition requires detailed insights how areas with specific gene activities and microanatomical architectures contribute to brain function and dysfunction. The Allen Human Brain Atlas contains regional gene expression data, while the JuBrain Atlas offers three-dimensional cytoarchitectonic maps reflecting interindividual variability. To date, an integrated framework that combines the analytical benefits of both scientific platforms towards a multi-level brain atlas of adult humans was not available. We have, therefore, developed JuGEx, a new method for integrating tissue transcriptome and cytoarchitectonic segregation. We investigated differential gene expression in two JuBrain areas of the frontal pole that we have structurally and functionally characterized in previous studies. Our results show a significant upregulation of MAOA and TAC1 in the medial area frontopolaris which is a node in the limbic-cortical network and known to be susceptible for gray matter loss and behavioral dysfunction in patients with depression. The MAOA gene encodes an enzyme which is involved in the catabolism of dopamine, norepinephrine, serotonin, and other monoaminergic neurotransmitters. The TAC1 locus generates hormones that play a role in neuron excitations and behavioral responses. Overall, JuGEx provides a new tool for the scientific community that empowers research from basic, cognitive and clinical neuroscience in brain regions and disease models with regard to gene expression.

Delivery of Nanotethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

DTIC Science & Technology

2016-12-01

medical images (CT). A critical advantage of a voxel-based code is not only to include tissue heterogeneities but to integrate medically acquired...transport in tissue based on the acquired medical images of an individual patient (CT and MRI) with sufficient accuracy and at accelerated rates for...Human Sciences (HHS) (2015). These latter awards provided Akshay the opportunity to present this research at the IEEE Medical Imaging (NSS/MIC 2014) and

VoxResNet: Deep voxelwise residual networks for brain segmentation from 3D MR images.

PubMed

Chen, Hao; Dou, Qi; Yu, Lequan; Qin, Jing; Heng, Pheng-Ann

2018-04-15

Segmentation of key brain tissues from 3D medical images is of great significance for brain disease diagnosis, progression assessment and monitoring of neurologic conditions. While manual segmentation is time-consuming, laborious, and subjective, automated segmentation is quite challenging due to the complicated anatomical environment of brain and the large variations of brain tissues. We propose a novel voxelwise residual network (VoxResNet) with a set of effective training schemes to cope with this challenging problem. The main merit of residual learning is that it can alleviate the degradation problem when training a deep network so that the performance gains achieved by increasing the network depth can be fully leveraged. With this technique, our VoxResNet is built with 25 layers, and hence can generate more representative features to deal with the large variations of brain tissues than its rivals using hand-crafted features or shallower networks. In order to effectively train such a deep network with limited training data for brain segmentation, we seamlessly integrate multi-modality and multi-level contextual information into our network, so that the complementary information of different modalities can be harnessed and features of different scales can be exploited. Furthermore, an auto-context version of the VoxResNet is proposed by combining the low-level image appearance features, implicit shape information, and high-level context together for further improving the segmentation performance. Extensive experiments on the well-known benchmark (i.e., MRBrainS) of brain segmentation from 3D magnetic resonance (MR) images corroborated the efficacy of the proposed VoxResNet. Our method achieved the first place in the challenge out of 37 competitors including several state-of-the-art brain segmentation methods. Our method is inherently general and can be readily applied as a powerful tool to many brain-related studies, where accurate segmentation of brain structures is critical. Copyright © 2017 Elsevier Inc. All rights reserved.

Differentiating pediatric epileptic brain tissue from normal brain tissue by using time-dependent diffuse reflectance spectroscopy in vivo: comprehensive data analysis method in the time domain

NASA Astrophysics Data System (ADS)

Oh, Sanghoon; Fernald, Bradley; Bhatia, Sanjiv; Ragheb, John; Sandberg, David; Johnson, Mahlon; Lin, Wei-Chiang

2009-05-01

This research investigated the feasibility of using time-dependent diffuse reflectance spectroscopy to differentiate pediatric epileptic brain tissue from normal brain tissue. The optical spectroscopic technique monitored the dynamic optical properties of the cerebral cortex that are associated with its physiological, morphological, and compositional characteristics. Due to the transient irregular epileptic discharge activity within the epileptic brain tissue it was hypothesized that the lesion would express abnormal dynamic optical behavior that would alter normal dynamic behavior. Thirteen pediatric epilepsy patients and seven pediatric brain tumor patients (normal controls) were recruited for this clinical study. Dynamic optical properties were obtained from the cortical surface intraoperatively using a timedependent diffuse reflectance spectroscopy system. This system consisted of a fiber-optic probe, a tungsten-halogen light source, and a spectrophotometer. It acquired diffuse reflectance spectra with a spectral range of 204 nm to 932 nm at a rate of 33 spectra per second for approximately 12 seconds. Biopsy samples were taken from electrophysiologically abnormal cortex and evaluated by a neuropathologist, which served as a gold standard for lesion classification. For data analysis, spectral intensity changes of diffuse reflectance in the time domain at two different wavelengths from each investigated site were compared. Negative correlation segment, defined by the periods where the intensity changes at the two wavelengths were opposite in their slope polarity, were extracted. The total duration of negative correlation, referred to as the "negative correlation time index", was calculated by integrating the negative correlation segments. The negative correlation time indices from all investigated sites were sub-grouped according to the corresponding histological classifications. The difference between the mean indices of two subgroups was evaluated by standard t-test. These comparison and calculation procedures were carried out for all possible wavelength combinations between 400 nm and 800 nm with 2 nm increments. The positive group consisted of seven pathologically abnormal test sites, and the negative group consisted of 13 normal test sites from non-epileptic tumor patients. A standard t-test showed significant difference between negative correlation time indices from the two groups at the wavelength combinations of 700-760 nm versus 550-580 nm. An empirical discrimination algorithm based on the negative correlation time indices in this range produced 100% sensitivity and 85% specificity. Based on these results time-dependent diffuse reflectance spectroscopy with optimized data analysis methods differentiates epileptic brain tissue from normal brain tissue adequately, therefore can be utilized for surgical guidance, and may enhance the surgical outcome of pediatric epilepsy surgery.

Phosphorylated recombinant HSP27 protects the brain and attenuates blood-brain barrier disruption following stroke in mice receiving intravenous tissue-plasminogen activator.

PubMed

Shimada, Yoshiaki; Shimura, Hideki; Tanaka, Ryota; Yamashiro, Kazuo; Koike, Masato; Uchiyama, Yasuo; Urabe, Takao; Hattori, Nobutaka

2018-01-01

Loss of integrity of the blood-brain barrier (BBB) in ischemic stroke victims initiates a devastating cascade of events causing brain damage. Maintaining the BBB is important to preserve brain function in ischemic stroke. Unfortunately, recombinant tissue plasminogen activator (tPA), the only effective fibrinolytic treatment at the acute stage of ischemic stroke, also injures the BBB and increases the risk of brain edema and secondary hemorrhagic transformation. Thus, it is important to identify compounds that maintain BBB integrity in the face of ischemic injury in patients with stroke. We previously demonstrated that intravenously injected phosphorylated recombinant heat shock protein 27 (prHSP27) protects the brains of mice with transient middle cerebral artery occlusion (tMCAO), an animal stroke-model. Here, we determined whether prHSP27, in addition to attenuating brain injury, also decreases BBB damage in hyperglycemic tMCAO mice that had received tPA. After induction of hyperglycemia and tMCAO, we examined 4 treatment groups: 1) bovine serum albumin (BSA), 2) prHSP27, 3) tPA, 4) tPA plus prHSP27. We examined the effects of prHSP27 by comparing the BSA and prHSP27 groups and the tPA and tPA plus prHSP27 groups. Twenty-four hours after injection, prHSP27 reduced infarct volume, brain swelling, neurological deficits, the loss of microvessel proteins and endothelial cell walls, and mortality. It also reduced the rates of hemorrhagic transformation, extravasation of endogenous IgG, and MMP-9 activity, signs of BBB damage. Therefore, prHSP27 injection attenuated brain damage and preserved the BBB in tPA-injected, hyperglycemic tMCAO experimental stroke-model mice, in which the BBB is even more severely damaged than in simple tMCAO mice. The attenuation of brain damage and BBB disruption in the presence of tPA suggests the effectiveness of prHSP27 and tPA as a combination therapy. prHSP27 may be a novel therapeutic agent for ischemic stroke patients whose BBBs are injured following tPA injections.

5-Aminolevulinic Acid Accumulation in a Cerebral Infarction Mimicking High-Grade Glioma.

PubMed

Behling, Felix; Hennersdorf, Florian; Bornemann, Antje; Tatagiba, Marcos; Skardelly, Marco

2016-08-01

5-Aminolevulinic acid (5-ALA) has become an integral part in the neurosurgical treatment of malignant glioma. Over time, several other tumor entities have been identified to metabolize 5-ALA and show a similar fluorescence pattern during surgical resection. This case report is the first description of 5-ALA accumulation in postischemic cerebral tissue. This evidence questions the assumption that 5-ALA accumulation in glioma is exclusively attributed to tumor infiltration. Instead, 5-ALA accumulation can also occur beyond the tumor borders and may be partially ascribed to inflammatory changes in the surrounding brain tissue. A 64-year old woman presented with episodes of apraxia and a ring-enhancing lesion in postcontrast T1-weighted magnetic resonance sequences suggestive of high grade glioma. Strong fluorescence was observed during 5-ALA-guided resection. However, although the frozen section was inconclusive, the final histopathologic examination revealed a stage II cerebral infarction. 5-ALA accumulation in postischemic cerebral tissue should be considered for intended supramarginal resections near eloquent brain regions. Therefore, sufficient preoperative imaging should regularly include magnetic resonance imaging spectroscopy and perfusion sequences to ascertain the proper diagnosis. Moreover, further research is warranted to determine the role of 5-ALA accumulation in postischemic and inflammatory brain tissue. Copyright © 2016 Elsevier Inc. All rights reserved.

Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism.

PubMed

Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

2016-03-11

Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism.

Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism

PubMed Central

Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

2016-01-01

Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism. PMID:26964832

Brain Mechanical Property Measurement Using MRE with Intrinsic Activation

PubMed Central

Pattison, Adam J.; McGarry, Matthew D.; Perreard, Irina M.; Swienckowski, Jessica G.; Eskey, Clifford J.; Lollis, S. Scott; Paulsen, Keith D.

2013-01-01

Problem Addressed Many pathologies alter the mechanical properties of tissue. Magnetic resonance elastography (MRE) has been developed to noninvasively characterize these quantities in vivo. Typically, small vibrations are induced in the tissue of interest with an external mechanical actuator. The resulting displacements are measured with phase contrast sequences and are then used to estimate the underlying mechanical property distribution. Several MRE studies have quantified brain tissue properties. However, the cranium and meninges, especially the dura, are very effective at damping externally applied vibrations from penetrating deeply into the brain. Here, we report a method, termed ‘intrinsic activation’, that eliminates the requirement for external vibrations by measuring the motion generated by natural blood vessel pulsation. Methodology A retrospectively gated phase contrast MR angiography sequence was used to record the tissue velocity at eight phases of the cardiac cycle. The velocities were numerically integrated via the Fourier transform to produce the harmonic displacements at each position within the brain. The displacements were then reconstructed into images of the shear modulus based on both linear elastic and poroelastic models. Results, Significance and Potential Impact The mechanical properties produced fall within the range of brain tissue estimates reported in the literature and, equally important, the technique yielded highly reproducible results. The mean shear modulus was 8.1 kPa for linear elastic reconstructions and 2.4 kPa for poroelastic reconstructions where fluid pressure carries a portion of the stress. Gross structures of the brain were visualized, particularly in the poroelastic reconstructions. Intra-subject variability was significantly less than the inter-subject variability in a study of 6 asymptomatic individuals. Further, larger changes in mechanical properties were observed in individuals when examined over time than when the MRE procedures were repeated on the same day. Cardiac pulsation, termed intrinsic activation, produces sufficient motion to allow mechanical properties to be recovered. The poroelastic model is more consistent with the measured data from brain at low frequencies than the linear elastic model. Intrinsic activation allows MR elastography to be performed without a device shaking the head so the patient notices no differences between it and the other sequences in an MR examination. PMID:23079508

Brain mechanical property measurement using MRE with intrinsic activation

NASA Astrophysics Data System (ADS)

Weaver, John B.; Pattison, Adam J.; McGarry, Matthew D.; Perreard, Irina M.; Swienckowski, Jessica G.; Eskey, Clifford J.; Lollis, S. Scott; Paulsen, Keith D.

2012-11-01

Many pathologies alter the mechanical properties of tissue. Magnetic resonance elastography (MRE) has been developed to noninvasively characterize these quantities in vivo. Typically, small vibrations are induced in the tissue of interest with an external mechanical actuator. The resulting displacements are measured with phase contrast sequences and are then used to estimate the underlying mechanical property distribution. Several MRE studies have quantified brain tissue properties. However, the cranium and meninges, especially the dura, are very effective at damping externally applied vibrations from penetrating deeply into the brain. Here, we report a method, termed ‘intrinsic activation’, that eliminates the requirement for external vibrations by measuring the motion generated by natural blood vessel pulsation. A retrospectively gated phase contrast MR angiography sequence was used to record the tissue velocity at eight phases of the cardiac cycle. The velocities were numerically integrated via the Fourier transform to produce the harmonic displacements at each position within the brain. The displacements were then reconstructed into images of the shear modulus based on both linear elastic and poroelastic models. The mechanical properties produced fall within the range of brain tissue estimates reported in the literature and, equally important, the technique yielded highly reproducible results. The mean shear modulus was 8.1 kPa for linear elastic reconstructions and 2.4 kPa for poroelastic reconstructions where fluid pressure carries a portion of the stress. Gross structures of the brain were visualized, particularly in the poroelastic reconstructions. Intra-subject variability was significantly less than the inter-subject variability in a study of six asymptomatic individuals. Further, larger changes in mechanical properties were observed in individuals when examined over time than when the MRE procedures were repeated on the same day. Cardiac pulsation, termed intrinsic activation, produces sufficient motion to allow mechanical properties to be recovered. The poroelastic model is more consistent with the measured data from brain at low frequencies than the linear elastic model. Intrinsic activation allows MRE to be performed without a device shaking the head so the patient notices no differences between it and the other sequences in an MR examination.

Atrophy of spared gray matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke.

PubMed

Gauthier, Lynne V; Taub, Edward; Mark, Victor W; Barghi, Ameen; Uswatte, Gitendra

2012-02-01

Although the motor deficit after stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to constraint-induced movement therapy in patients with chronic stroke may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Voxel-based morphometry analysis was performed on MRI scans from 80 patients with chronic stroke to investigate whether variations in gray matter density were correlated with extent of residual motor impairment or with constraint-induced movement therapy-induced motor recovery. Decreased gray matter density in noninfarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced gray matter density in multiple remote brain regions predicted a lesser extent of motor improvement from constraint-induced movement therapy. Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke.

Atrophy of spared grey matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke

PubMed Central

Gauthier, Lynne V.; Taub, Edward; Mark, Victor W.; Barghi, Ameen; Uswatte, Gitendra

2011-01-01

Background and Purpose Although the motor deficit following stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to Constraint-Induced Movement therapy (CI therapy) in chronic stroke patients may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Methods Voxel-based morphometry (VBM) analysis was performed on MRI scans from 80 chronic stroke patients to investigate whether variations in grey matter density were correlated with extent of residual motor impairment or with CI therapy-induced motor recovery. Results Decreased grey matter density in non-infarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced grey matter density in multiple remote brain regions predicted a lesser extent of motor improvement from CI therapy. Conclusions Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke. PMID:22096036

A new graphic plot analysis for determination of neuroreceptor binding in positron emission tomography studies.

PubMed

Ito, Hiroshi; Yokoi, Takashi; Ikoma, Yoko; Shidahara, Miho; Seki, Chie; Naganawa, Mika; Takahashi, Hidehiko; Takano, Harumasa; Kimura, Yuichi; Ichise, Masanori; Suhara, Tetsuya

2010-01-01

In positron emission tomography (PET) studies with radioligands for neuroreceptors, tracer kinetics have been described by the standard two-tissue compartment model that includes the compartments of nondisplaceable binding and specific binding to receptors. In the present study, we have developed a new graphic plot analysis to determine the total distribution volume (V(T)) and nondisplaceable distribution volume (V(ND)) independently, and therefore the binding potential (BP(ND)). In this plot, Y(t) is the ratio of brain tissue activity to time-integrated arterial input function, and X(t) is the ratio of time-integrated brain tissue activity to time-integrated arterial input function. The x-intercept of linear regression of the plots for early phase represents V(ND), and the x-intercept of linear regression of the plots for delayed phase after the equilibrium time represents V(T). BP(ND) can be calculated by BP(ND)=V(T)/V(ND)-1. Dynamic PET scanning with measurement of arterial input function was performed on six healthy men after intravenous rapid bolus injection of [(11)C]FLB457. The plot yielded a curve in regions with specific binding while it yielded a straight line through all plot data in regions with no specific binding. V(ND), V(T), and BP(ND) values calculated by the present method were in good agreement with those by conventional non-linear least-squares fitting procedure. This method can be used to distinguish graphically whether the radioligand binding includes specific binding or not.

Optimization of Treatment Geometry to Reduce Normal Brain Dose in Radiosurgery of Multiple Brain Metastases with Single-Isocenter Volumetric Modulated Arc Therapy.

PubMed

Wu, Qixue; Snyder, Karen Chin; Liu, Chang; Huang, Yimei; Zhao, Bo; Chetty, Indrin J; Wen, Ning

2016-09-30

Treatment of patients with multiple brain metastases using a single-isocenter volumetric modulated arc therapy (VMAT) has been shown to decrease treatment time with the tradeoff of larger low dose to the normal brain tissue. We have developed an efficient Projection Summing Optimization Algorithm to optimize the treatment geometry in order to reduce dose to normal brain tissue for radiosurgery of multiple metastases with single-isocenter VMAT. The algorithm: (a) measures coordinates of outer boundary points of each lesion to be treated using the Eclipse Scripting Application Programming Interface, (b) determines the rotations of couch, collimator, and gantry using three matrices about the cardinal axes, (c) projects the outer boundary points of the lesion on to Beam Eye View projection plane, (d) optimizes couch and collimator angles by selecting the least total unblocked area for each specific treatment arc, and (e) generates a treatment plan with the optimized angles. The results showed significant reduction in the mean dose and low dose volume to normal brain, while maintaining the similar treatment plan qualities on the thirteen patients treated previously. The algorithm has the flexibility with regard to the beam arrangements and can be integrated in the treatment planning system for clinical application directly.

Intraoperative brain hemodynamic response assessment with real-time hyperspectral optical imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Laurence, Audrey; Pichette, Julien; Angulo-Rodríguez, Leticia M.; Saint Pierre, Catherine; Lesage, Frédéric; Bouthillier, Alain; Nguyen, Dang Khoa; Leblond, Frédéric

2016-03-01

Following normal neuronal activity, there is an increase in cerebral blood flow and cerebral blood volume to provide oxygenated hemoglobin to active neurons. For abnormal activity such as epileptiform discharges, this hemodynamic response may be inadequate to meet the high metabolic demands. To verify this hypothesis, we developed a novel hyperspectral imaging system able to monitor real-time cortical hemodynamic changes during brain surgery. The imaging system is directly integrated into a surgical microscope, using the white-light source for illumination. A snapshot hyperspectral camera is used for detection (4x4 mosaic filter array detecting 16 wavelengths simultaneously). We present calibration experiments where phantoms made of intralipid and food dyes were imaged. Relative concentrations of three dyes were recovered at a video rate of 30 frames per second. We also present hyperspectral recordings during brain surgery of epileptic patients with concurrent electrocorticography recordings. Relative concentration maps of oxygenated and deoxygenated hemoglobin were extracted from the data, allowing real-time studies of hemodynamic changes with a good spatial resolution. Finally, we present preliminary results on phantoms obtained with an integrated spatial frequency domain imaging system to recover tissue optical properties. This additional module, used together with the hyperspectral imaging system, will allow quantification of hemoglobin concentrations maps. Our hyperspectral imaging system offers a new tool to analyze hemodynamic changes, especially in the case of epileptiform discharges. It also offers an opportunity to study brain connectivity by analyzing correlations between hemodynamic responses of different tissue regions.

Molecular networks and the evolution of human cognitive specializations.

PubMed

Fontenot, Miles; Konopka, Genevieve

2014-12-01

Inroads into elucidating the origins of human cognitive specializations have taken many forms, including genetic, genomic, anatomical, and behavioral assays that typically compare humans to non-human primates. While the integration of all of these approaches is essential for ultimately understanding human cognition, here, we review the usefulness of coexpression network analysis for specifically addressing this question. An increasing number of studies have incorporated coexpression networks into brain expression studies comparing species, disease versus control tissue, brain regions, or developmental time periods. A clearer picture has emerged of the key genes driving brain evolution, as well as the developmental and regional contributions of gene expression patterns important for normal brain development and those misregulated in cognitive diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Banking brain tissue for research.

PubMed

Klioueva, Natasja; Bovenberg, Jasper; Huitinga, Inge

2017-01-01

Well-characterized human brain tissue is crucial for scientific breakthroughs in research of the human brain and brain diseases. However, the collection, characterization, management, and accessibility of brain human tissue are rather complex. Well-characterized human brain tissue is often provided from private, sometimes small, brain tissue collections by (neuro)pathologic experts. However, to meet the increasing demand for human brain tissue from the scientific community, many professional brain-banking activities aiming at both neurologic and psychiatric diseases as well as healthy controls are currently being initiated worldwide. Professional biobanks are open-access and in many cases run donor programs. They are therefore costly and need effective business plans to guarantee long-term sustainability. Here we discuss the ethical, legal, managerial, and financial aspects of professional brain banks. Copyright © 2017 Elsevier B.V. All rights reserved.

Transcriptional insulation of the human keratin 18 gene in transgenic mice.

PubMed Central

Neznanov, N; Thorey, I S; Ceceña, G; Oshima, R G

1993-01-01

Expression of the 10-kb human keratin 18 (K18) gene in transgenic mice results in efficient and appropriate tissue-specific expression in a variety of internal epithelial organs, including liver, lung, intestine, kidney, and the ependymal epithelium of brain, but not in spleen, heart, or skeletal muscle. Expression at the RNA level is directly proportional to the number of integrated K18 transgenes. These results indicate that the K18 gene is able to insulate itself both from the commonly observed cis-acting effects of the sites of integration and from the potential complications of duplicated copies of the gene arranged in head-to-tail fashion. To begin to identify the K18 gene sequences responsible for this property of transcriptional insulation, additional transgenic mouse lines containing deletions of either the 5' or 3' distal end of the K18 gene have been characterized. Deletion of 1.5 kb of the distal 5' flanking sequence has no effect upon either the tissue specificity or the copy number-dependent behavior of the transgene. In contrast, deletion of the 3.5-kb 3' flanking sequence of the gene results in the loss of the copy number-dependent behavior of the gene in liver and intestine. However, expression in kidney, lung, and brain remains efficient and copy number dependent in these transgenic mice. Furthermore, herpes simplex virus thymidine kinase gene expression is copy number dependent in transgenic mice when the gene is located between the distal 5'- and 3'-flanking sequences of the K18 gene. Each adult transgenic male expressed the thymidine kinase gene in testes and brain and proportionally to the number of integrated transgenes. We conclude that the characteristic of copy number-dependent expression of the K18 gene is tissue specific because the sequence requirements for transcriptional insulation in adult liver and intestine are different from those for lung and kidney. In addition, the behavior of the transgenic thymidine kinase gene in testes and brain suggests that the property of transcriptional insulation of the K18 gene may be conferred by the distal flanking sequences of the K18 gene and, additionally, may function for other genes. Images PMID:7681143

Regional Brain Tissue Changes and Associations with Disease Severity in Children with Sleep Disordered Breathing.

PubMed

Horne, Rosemary S C; Roy, Bhaswati; Walter, Lisa M; Biggs, Sarah N; Tamanyan, Knarik; Weichard, Aidan; Nixon, Gillian M; Davey, Margot J; Ditchfield, Michael; Harper, Ronald M; Kumar, Rajesh

2017-12-15

Children with sleep-disordered breathing (SDB) exhibit behavioral, cognitive, and autonomic deficits, suggestive of neural injury. We assessed whether the tissue alterations resulted from acute or chronic processes, and if alterations correlated with disease severity. Brain tissue integrity was examined with mean diffusivity (MD) (3.0-Tesla scanner) in 20 non-snoring controls (mean age±sem, 12.2±0.6y; 10 male) and 18 children with SDB (12.3±0.7y; 11 male). Sleep, cognitive, and behavioral measures were compared between groups following overnight polysomnography using Student's t-tests. Whole-brain MD maps were realigned and averaged, normalized, smoothed, and compared between groups using ANCOVA (covariates; age, gender, and socioeconomic status). Partial correlations were calculated between whole-brain smoothed MD maps and obstructive apnea hypopnea indices (OAHI). Age, gender, and sleep variables did not differ between groups. The SDB group showed higher OAHI, body mass indices, and systolic blood pressure. Significantly reduced MD values (acute changes) appeared in the hippocampus, insula, thalamus, temporal and occipital cortices, and cerebellum, but were increased (chronic damage) in the frontal and prefrontal cortices in the SDB group over controls. Both positive and negative correlations appeared with extent of tissue changes and disease severity. Externalizing and Total Problem Behaviors were significantly higher in SDB children. Verbal, performance and total IQ scores trended lower, and behavioral scores trended higher. Pediatric SDB is accompanied by predominantly acute brain changes in areas that regulate autonomic, cognitive, and mood functions, and chronic changes in frontal cortices essential for behavioral control. Interventions need to be keyed to address acute vs chronic injury. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

The presence of both negative and positive elements in the 5'-flanking sequence of the rat Na,K-ATPase alpha 3 subunit gene are required for brain expression in transgenic mice.

PubMed Central

Pathak, B G; Neumann, J C; Croyle, M L; Lingrel, J B

1994-01-01

The Na,K-ATPase is an integral plasma membrane protein consisting of alpha and beta subunits, each of which has discrete isoforms expressed in a tissue-specific manner. Of the three functional alpha isoform genes, the one encoding the alpha 3 isoform is the most tissue-restricted in its expression, being found primarily in the brain. To identify regions of the alpha 3 isoform gene that are involved in directing expression in the brain, a 1.6 kb 5'-flanking sequence was attached to a reporter gene, chloramphenicol acetyltransferase (CAT). The alpha 3-CAT chimeric gene construct was microinjected into fertilized mouse eggs, and transgenic mice were produced. Analysis of adult transgenic mice from different lines revealed that the transgene is expressed primarily in the brain. To further delineate regions that are needed for conferring expression in this tissue, systematic deletions of the 5'-flanking sequence of the alpha 3-CAT fusion constructs were made and analyzed, again using transgenic mice. The results from these analyses indicate that DNA sequences required for mediating brain-specific expression of the alpha 3 isoform gene are present within 210 bp upstream of the transcription initiation site. alpha 3-CAT promoter constructs containing scanning mutations in this region were also assayed in transgenic mice. These studies have identified both a functional neural-restrictive silencer element as well as a positively acting cis element. Images PMID:7984427

TU-G-210-01: Modeling for Breast and Brain HIFU Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christensen, D.

Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such asmore » the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)« less

Wireless and batteryless biomedical microsystem for neural recording and epilepsy suppression based on brain focal cooling.

PubMed

Hou, K-C; Chang, C-W; Chiou, J-C; Huang, Y-H; Shaw, F-Z

2011-12-01

This work presents a biomedical microsystem with a wireless radiofrequency (RF)-powered electronics and versatile sensors/actuators for use in nanomedicinal diagnosis and therapy. The cooling of brain tissue has the potential to reduce the frequency and severity of epilepsy. Miniaturised spiral coils as a wireless power module with low-dropout linear regulator circuit convert RF signals into a DC voltage, can be implanted without a battery in monitoring free behaviour. A thermoelectric (TE) cooler is an actuator that is employed to cool down brain tissue to suppress epilepsy. Electroencephalogram (EEG) electrodes and TE coolers are integrated to form module that is placed inside the head of a rat and fastened with a bio-compatible material. EEG signals are used to identify waveforms associated with epilepsy and are measured using readout circuits. The wireless part of the presented design achieves a low quiescent current and line/load regulation and high antenna/current efficiency with thermal protection to avoid damage to the implanted tissue. Epilepsy is suppressed by reducing the temperature to reduce the duration of this epileptic episode. Related characterisations demonstrate that the proposed design can be adopted in an effective nanomedicine microsystem.

Effect of vitro preservation on mechanical properties of brain tissue

NASA Astrophysics Data System (ADS)

Zhang, Wei; Liu, Yi-fan; Liu, Li-fu; Niu, Ying; Ma, Jian-li; Wu, Cheng-wei

2017-05-01

To develop the protective devices for preventing traumatic brain injuries, it requires the accurate characterization of the mechanical properties of brain tissue. For this, it necessary to elucidate the effect of vitro preservation on the mechanical performance of brain tissue as usually the measurements are carried out in vitro. In this paper, the thermal behavior of brain tissue preserved for various period of time was first investigated and the mechanical properties were also measured. Both reveals the deterioration with prolonged preservation duration. The observations of brain tissue slices indicates the brain tissue experiences karyorrhexis and karyorrhexis in sequence, which accounts for the deterioration phenomena.

76 FR 54778 - Center For Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-02

..., Musculoskeletal Tissue Engineering Study Section. Date: September 29-30, 2011. Time: 8 a.m. to 5 p.m. Agenda: [email protected] . Name of Committee: Brain Disorders and Clinical Neuroscience Integrated Review Group, Clinical Neuroscience and Neurodegeneration Study Section. Date: October 5-6, 2011. Time: 8 a.m. to 5 p.m...

Identification and Characterization of Long Non-Coding RNAs Related to Mouse Embryonic Brain Development from Available Transcriptomic Data

PubMed Central

He, Hongjuan; Xiu, Youcheng; Guo, Jing; Liu, Hui; Liu, Qi; Zeng, Tiebo; Chen, Yan; Zhang, Yan; Wu, Qiong

2013-01-01

Long non-coding RNAs (lncRNAs) as a key group of non-coding RNAs have gained widely attention. Though lncRNAs have been functionally annotated and systematic explored in higher mammals, few are under systematical identification and annotation. Owing to the expression specificity, known lncRNAs expressed in embryonic brain tissues remain still limited. Considering a large number of lncRNAs are only transcribed in brain tissues, studies of lncRNAs in developmental brain are therefore of special interest. Here, publicly available RNA-sequencing (RNA-seq) data in embryonic brain are integrated to identify thousands of embryonic brain lncRNAs by a customized pipeline. A significant proportion of novel transcripts have not been annotated by available genomic resources. The putative embryonic brain lncRNAs are shorter in length, less spliced and show less conservation than known genes. The expression of putative lncRNAs is in one tenth on average of known coding genes, while comparable with known lncRNAs. From chromatin data, putative embryonic brain lncRNAs are associated with active chromatin marks, comparable with known lncRNAs. Embryonic brain expressed lncRNAs are also indicated to have expression though not evident in adult brain. Gene Ontology analysis of putative embryonic brain lncRNAs suggests that they are associated with brain development. The putative lncRNAs are shown to be related to possible cis-regulatory roles in imprinting even themselves are deemed to be imprinted lncRNAs. Re-analysis of one knockdown data suggests that four regulators are associated with lncRNAs. Taken together, the identification and systematic analysis of putative lncRNAs would provide novel insights into uncharacterized mouse non-coding regions and the relationships with mammalian embryonic brain development. PMID:23967161

Brain Volume as an Integrated Marker for the Risk of Death in a Community-Based Sample: Age Gene/Environment Susceptibility--Reykjavik Study.

PubMed

Van Elderen, Saskia S G C; Zhang, Qian; Sigurdsson, Sigudur; Haight, Thaddeus J; Lopez, Oscar; Eiriksdottir, Gudny; Jonsson, Palmi; de Jong, Laura; Harris, Tamara B; Garcia, Melissa; Gudnason, Vilmundar; van Buchem, Mark A; Launer, Lenore J

2016-01-01

Total brain volume is an integrated measure of health and may be an independent indicator of mortality risk independent of any one clinical or subclinical disease state. We investigate the association of brain volume to total and cause-specific mortality in a large nondemented stroke-free community-based cohort. The analysis includes 3,543 men and women (born 1907-1935) participating in the Age, Gene, Environment Susceptibility-Reykjavik Study. Participants with a known brain-related high risk for mortality (cognitive impairment or stroke) were excluded from these analyses. Quantitative estimates of total brain volume, white matter, white matter lesions, total gray matter (GM; cortical GM and subcortical GM separately), and focal cerebral vascular disease were generated from brain magnetic resonance imaging. Brain atrophy was expressed as brain tissue volume divided by total intracranial volume, yielding a percentage. Mean follow-up duration was 7.2 (0-10) years, with 647 deaths. Cox regression was used to analyze the association of mortality to brain atrophy, adjusting for demographics, cardiovascular risk factors, and cerebral vascular disease. Reduced risk of mortality was significantly associated with higher total brain volume (hazard ratio, 95% confidence interval = 0.71, 0.65-0.78), white matter (0.85, 0.78-0.93), total GM (0.74, 0.68-0.81), and cortical GM (0.78, 0.70-0.87). Overall, the associations were similar for cardiovascular and noncardiovascular-related deaths. Independent of multiple risk factors and cerebral vascular damage, global brain volume predicts mortality in a large nondemented stroke-free community-dwelling older cohort. Total brain volume may be an integrated measure reflecting a range of health and with further investigation could be a useful clinical tool when assessing risk for mortality. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.

Neurogenesis in the aging brain.

PubMed

Apple, Deana M; Solano-Fonseca, Rene; Kokovay, Erzsebet

2017-10-01

Adult neurogenesis is the process of producing new neurons from neural stem cells (NSCs) for integration into the brain circuitry. Neurogenesis occurs throughout life in the ventricular-subventricular zone (V-SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus. However, during aging, NSCs and their progenitors exhibit reduced proliferation and neuron production, which is thought to contribute to age-related cognitive impairment and reduced plasticity that is necessary for some types of brain repair. In this review, we describe NSCs and their niches during tissue homeostasis and how they undergo age-associated remodeling and dysfunction. We also discuss some of the functional ramifications in the brain from NSC aging. Finally, we discuss some recent insights from interventions in NSC aging that could eventually translate into therapies for healthy brain aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Brown adipose tissue thermogenesis, the basic rest-activity cycle, meal initiation, and bodily homeostasis in rats.

PubMed

Blessing, William; Mohammed, Mazher; Ootsuka, Youichirou

2013-09-10

Laboratory rats alternate between behaviorally active and inactive states every 1-2h throughout the 24hour day, the ultradian basic rest-activity cycle (BRAC). During the behaviorally active phases of the BRAC, brown adipose tissue (BAT) temperature, body and brain temperature, and arterial pressure and heart rate increase in an integrated manner. Since the BAT temperature increases are substantially greater than the corresponding body and brain temperature increases, BAT thermogenesis contributes to the body and brain temperature increases. When food is available ad libitum, eating commences approximately 15min after the onset of an episodic increase in BAT temperature, and not at other times. If no food is available, the rat still disturbs the empty food container approximately 15min after the onset of an episodic increase in BAT temperature, and not at other times. The increase in brain temperature that precedes eating may facilitate the cognitive processing that occurs during the search for food, when the rat engages with the external environment. Rather than being triggered by changes in levels of body fuels or other meal-associated factors, in sedentary laboratory rats with ad libitum access to food, meal initiation normally occurs as part of the centrally-programmed ultradian BRAC. BRAC-associated BAT temperature increases occur in a thermoneutral environment and they are not preceded by falls in body or brain temperature, so they are not homeostatic thermoregulatory responses. The pattern of integrated behaviors and physiological functions associated with the BRAC presumably reflects Darwinian natural selection, and homeostatic thermoregulatory explanations of the BRAC-associated changes in temperature should be considered in this context. Copyright © 2013 Elsevier Inc. All rights reserved.

Prediction of brain-computer interface aptitude from individual brain structure.

PubMed

Halder, S; Varkuti, B; Bogdan, M; Kübler, A; Rosenstiel, W; Sitaram, R; Birbaumer, N

2013-01-01

Brain-computer interface (BCI) provide a non-muscular communication channel for patients with impairments of the motor system. A significant number of BCI users is unable to obtain voluntary control of a BCI-system in proper time. This makes methods that can be used to determine the aptitude of a user necessary. We hypothesized that integrity and connectivity of involved white matter connections may serve as a predictor of individual BCI-performance. Therefore, we analyzed structural data from anatomical scans and DTI of motor imagery BCI-users differentiated into high and low BCI-aptitude groups based on their overall performance. Using a machine learning classification method we identified discriminating structural brain trait features and correlated the best features with a continuous measure of individual BCI-performance. Prediction of the aptitude group of each participant was possible with near perfect accuracy (one error). Tissue volumetric analysis yielded only poor classification results. In contrast, the structural integrity and myelination quality of deep white matter structures such as the Corpus Callosum, Cingulum, and Superior Fronto-Occipital Fascicle were positively correlated with individual BCI-performance. This confirms that structural brain traits contribute to individual performance in BCI use.

Prediction of brain-computer interface aptitude from individual brain structure

PubMed Central

Halder, S.; Varkuti, B.; Bogdan, M.; Kübler, A.; Rosenstiel, W.; Sitaram, R.; Birbaumer, N.

2013-01-01

Objective: Brain-computer interface (BCI) provide a non-muscular communication channel for patients with impairments of the motor system. A significant number of BCI users is unable to obtain voluntary control of a BCI-system in proper time. This makes methods that can be used to determine the aptitude of a user necessary. Methods: We hypothesized that integrity and connectivity of involved white matter connections may serve as a predictor of individual BCI-performance. Therefore, we analyzed structural data from anatomical scans and DTI of motor imagery BCI-users differentiated into high and low BCI-aptitude groups based on their overall performance. Results: Using a machine learning classification method we identified discriminating structural brain trait features and correlated the best features with a continuous measure of individual BCI-performance. Prediction of the aptitude group of each participant was possible with near perfect accuracy (one error). Conclusions: Tissue volumetric analysis yielded only poor classification results. In contrast, the structural integrity and myelination quality of deep white matter structures such as the Corpus Callosum, Cingulum, and Superior Fronto-Occipital Fascicle were positively correlated with individual BCI-performance. Significance: This confirms that structural brain traits contribute to individual performance in BCI use. PMID:23565083

Spatially resolved proteome mapping of laser capture microdissected tissue with automated sample transfer to nanodroplets.

PubMed

Zhu, Ying; Dou, Maowei; Piehowski, Paul D; Liang, Yiran; Wang, Fangjun; Chu, Rosalie K; Chrisler, Will; Smith, Jordan N; Schwarz, Kaitlynn C; Shen, Yufeng; Shukla, Anil K; Moore, Ronald J; Smith, Richard D; Qian, Wei-Jun; Kelly, Ryan T

2018-06-24

Current mass spectrometry (MS)-based proteomics approaches are ineffective for mapping protein expression in tissue sections with high spatial resolution due to the limited overall sensitivity of conventional workflows. Here we report an integrated and automated method to advance spatially resolved proteomics by seamlessly coupling laser capture microdissection (LCM) with a recently developed nanoliter-scale sample preparation system termed nanoPOTS (Nanodroplet Processing in One pot for Trace Samples). The workflow is enabled by prepopulating nanowells with DMSO, which serves as a sacrificial capture liquid for microdissected tissues. The DMSO droplets efficiently collect laser-pressure catapulted LCM tissues as small as 20 µm in diameter with success rates >87%. We also demonstrate that tissue treatment with DMSO can significantly improve proteome coverage, likely due to its ability to dissolve lipids from tissue and enhance protein extraction efficiency. The LCM-nanoPOTS platform was able to identify 180, 695, and 1827 protein groups on average from 12-µm-thick rat brain cortex tissue sections with diameters of 50, 100, and 200 µm, respectively. We also analyzed 100-µm-diameter sections corresponding to 10-18 cells from three different regions of rat brain and comparatively quantified ~1000 proteins, demonstrating the potential utility for high-resolution spatially resolved mapping of protein expression in tissues. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Multichannel optical brain imaging to separate cerebral vascular, tissue metabolic, and neuronal effects of cocaine

NASA Astrophysics Data System (ADS)

Ren, Hugang; Luo, Zhongchi; Yuan, Zhijia; Pan, Yingtian; Du, Congwu

2012-02-01

Characterization of cerebral hemodynamic and oxygenation metabolic changes, as well neuronal function is of great importance to study of brain functions and the relevant brain disorders such as drug addiction. Compared with other neuroimaging modalities, optical imaging techniques have the potential for high spatiotemporal resolution and dissection of the changes in cerebral blood flow (CBF), blood volume (CBV), and hemoglobing oxygenation and intracellular Ca ([Ca2+]i), which serves as markers of vascular function, tissue metabolism and neuronal activity, respectively. Recently, we developed a multiwavelength imaging system and integrated it into a surgical microscope. Three LEDs of λ1=530nm, λ2=570nm and λ3=630nm were used for exciting [Ca2+]i fluorescence labeled by Rhod2 (AM) and sensitizing total hemoglobin (i.e., CBV), and deoxygenated-hemoglobin, whereas one LD of λ1=830nm was used for laser speckle imaging to form a CBF mapping of the brain. These light sources were time-sharing for illumination on the brain and synchronized with the exposure of CCD camera for multichannel images of the brain. Our animal studies indicated that this optical approach enabled simultaneous mapping of cocaine-induced changes in CBF, CBV and oxygenated- and deoxygenated hemoglobin as well as [Ca2+]i in the cortical brain. Its high spatiotemporal resolution (30μm, 10Hz) and large field of view (4x5 mm2) are advanced as a neuroimaging tool for brain functional study.

Quantitative MRI reveals the elderly ischemic brain is susceptible to increased early blood–brain barrier permeability following tissue plasminogen activator related to claudin 5 and occludin disassembly

PubMed Central

Kaur, Jaspreet; Tuor, Ursula I; Zhao, Zonghang; Barber, Philip A

2011-01-01

Great uncertainty exists as to whether aging enhances the detrimental effects of tissue plasminogen activator (tPA) on vascular integrity of the ischemic brain. We hypothesized that tPA treatment would augment ischemic injury by causing increased blood–brain barrier (BBB) breakdown as determined by quantitative serial T1 and T2 magnetic resonance imaging (MRI), and the transfer constant for gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) from blood to brain in aged (18 to 20 months) compared with young (3 to 4 months) Wistar rats after middle cerebral artery occlusion, mediated through the acute disassembly of claudin 5 and occludin. Increased T2 values over the first hour of postreperfusion were independently augmented following treatment with tPA (P<0.001) and aging (P<0.01), supporting a synergistic effect of tPA on the aged ischemic brain. Blood–brain barrier permeability for Gd-DTPA (KGd) was substantial following reperfusion in all animal groups and was exacerbated by tPA treatment in the elderly rat (P<0.001). The frequency of hematoma formation was proportionately increased in the elderly ischemic brain (P<0.05). Both tPA and age independently increased claudin 5 and occludin phosphorylation during ischemia. Early BBB permeability detected by quantitative MRI following ischemic stroke is enhanced by increased age and tPA and is related to claudin 5 and occludin phosphorylation. PMID:21610723

Selective Targeting of Brain Tumors with Gold Nanoparticle-Induced Radiosensitization

PubMed Central

Joh, Daniel Y.; Sun, Lova; Stangl, Melissa; Al Zaki, Ajlan; Murty, Surya; Santoiemma, Phillip P.; Davis, James J.; Baumann, Brian C.; Alonso-Basanta, Michelle; Bhang, Dongha; Kao, Gary D.; Tsourkas, Andrew; Dorsey, Jay F.

2013-01-01

Successful treatment of brain tumors such as glioblastoma multiforme (GBM) is limited in large part by the cumulative dose of Radiation Therapy (RT) that can be safely given and the blood-brain barrier (BBB), which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, the overall prognosis remains grim. Herein, we report our pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs). GNPs significantly increased cellular DNA damage inflicted by ionizing radiation in human GBM-derived cell lines and resulted in reduced clonogenic survival (with dose-enhancement ratio of ∼1.3). Intriguingly, combined GNP and RT also resulted in markedly increased DNA damage to brain blood vessels. Follow-up in vitro experiments confirmed that the combination of GNP and RT resulted in considerably increased DNA damage in brain-derived endothelial cells. Finally, the combination of GNP and RT increased survival of mice with orthotopic GBM tumors. Prior treatment of mice with brain tumors resulted in increased extravasation and in-tumor deposition of GNP, suggesting that RT-induced BBB disruption can be leveraged to improve the tumor-tissue targeting of GNP and thus further optimize the radiosensitization of brain tumors by GNP. These exciting results together suggest that GNP may be usefully integrated into the RT treatment of brain tumors, with potential benefits resulting from increased tumor cell radiosensitization to preferential targeting of tumor-associated vasculature. PMID:23638079

Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics.

PubMed

Kim, Dae-Hyeong; Viventi, Jonathan; Amsden, Jason J; Xiao, Jianliang; Vigeland, Leif; Kim, Yun-Soung; Blanco, Justin A; Panilaitis, Bruce; Frechette, Eric S; Contreras, Diego; Kaplan, David L; Omenetto, Fiorenzo G; Huang, Yonggang; Hwang, Keh-Chih; Zakin, Mitchell R; Litt, Brian; Rogers, John A

2010-06-01

Electronics that are capable of intimate, non-invasive integration with the soft, curvilinear surfaces of biological tissues offer important opportunities for diagnosing and treating disease and for improving brain/machine interfaces. This article describes a material strategy for a type of bio-interfaced system that relies on ultrathin electronics supported by bioresorbable substrates of silk fibroin. Mounting such devices on tissue and then allowing the silk to dissolve and resorb initiates a spontaneous, conformal wrapping process driven by capillary forces at the biotic/abiotic interface. Specialized mesh designs and ultrathin forms for the electronics ensure minimal stresses on the tissue and highly conformal coverage, even for complex curvilinear surfaces, as confirmed by experimental and theoretical studies. In vivo, neural mapping experiments on feline animal models illustrate one mode of use for this class of technology. These concepts provide new capabilities for implantable and surgical devices.

Regenerative Therapies for Central Nervous System Diseases: a Biomaterials Approach

PubMed Central

Tam, Roger Y; Fuehrmann, Tobias; Mitrousis, Nikolaos; Shoichet, Molly S

2014-01-01

The central nervous system (CNS) has a limited capacity to spontaneously regenerate following traumatic injury or disease, requiring innovative strategies to promote tissue and functional repair. Tissue regeneration strategies, such as cell and/or drug delivery, have demonstrated promising results in experimental animal models, but have been difficult to translate clinically. The efficacy of cell therapy, which involves stem cell transplantation into the CNS to replace damaged tissue, has been limited due to low cell survival and integration upon transplantation, while delivery of therapeutic molecules to the CNS using conventional methods, such as oral and intravenous administration, have been limited by diffusion across the blood–brain/spinal cord-barrier. The use of biomaterials to promote graft survival and integration as well as localized and sustained delivery of biologics to CNS injury sites is actively being pursued. This review will highlight recent advances using biomaterials as cell- and drug-delivery vehicles for CNS repair. PMID:24002187

Dissolvable Films of Silk Fibroin for Ultrathin, Conformal Bio-Integrated Electronics

PubMed Central

Kim, Dae-Hyeong; Viventi, Jonathan; Amsden, Jason J.; Xiao, Jianliang; Vigeland, Leif; Kim, Yun-Soung; Blanco, Justin A.; Panilaitis, Bruce; Frechette, Eric S.; Contreras, Diego; Kaplan, David L.; Omenetto, Fiorenzo G.; Huang, Yonggang; Hwang, Keh-Chih; Zakin, Mitchell R.; Litt, Brian; Rogers, John A.

2011-01-01

Electronics that are capable of intimate, non-invasive integration with the soft, curvilinear surfaces of biological tissues offer important opportunities for diagnosing and treating disease and for improving brain-machine interfaces. This paper describes a material strategy for a type of bio-interfaced system that relies on ultrathin electronics supported by bioresorbable substrates of silk fibroin. Mounting such devices on tissue and then allowing the silk to dissolve and resorb initiates a spontaneous, conformal wrapping process driven by capillary forces at the biotic/abiotic interface. Specialized mesh designs and ultrathin forms for the electronics ensure minimal stresses on the tissue and highly conformal coverage, even for complex curvilinear surfaces, as confirmed by experimental and theoretical studies. In vivo, neural mapping experiments on feline animal models illustrate one mode of use for this class of technology. These concepts provide new capabilities for implantable or surgical devices. PMID:20400953

Dissolvable films of silk fibroin for ultrathin conformal bio-integrated electronics

NASA Astrophysics Data System (ADS)

Kim, Dae-Hyeong; Viventi, Jonathan; Amsden, Jason J.; Xiao, Jianliang; Vigeland, Leif; Kim, Yun-Soung; Blanco, Justin A.; Panilaitis, Bruce; Frechette, Eric S.; Contreras, Diego; Kaplan, David L.; Omenetto, Fiorenzo G.; Huang, Yonggang; Hwang, Keh-Chih; Zakin, Mitchell R.; Litt, Brian; Rogers, John A.

2010-06-01

Electronics that are capable of intimate, non-invasive integration with the soft, curvilinear surfaces of biological tissues offer important opportunities for diagnosing and treating disease and for improving brain/machine interfaces. This article describes a material strategy for a type of bio-interfaced system that relies on ultrathin electronics supported by bioresorbable substrates of silk fibroin. Mounting such devices on tissue and then allowing the silk to dissolve and resorb initiates a spontaneous, conformal wrapping process driven by capillary forces at the biotic/abiotic interface. Specialized mesh designs and ultrathin forms for the electronics ensure minimal stresses on the tissue and highly conformal coverage, even for complex curvilinear surfaces, as confirmed by experimental and theoretical studies. In vivo, neural mapping experiments on feline animal models illustrate one mode of use for this class of technology. These concepts provide new capabilities for implantable and surgical devices.

Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program

PubMed Central

Beach, Thomas G.; Adler, Charles H.; Sue, Lucia I.; Serrano, Geidy; Shill, Holly A.; Walker, Douglas G.; Lue, LihFen; Roher, Alex E.; Dugger, Brittany N.; Maarouf, Chera; Birdsill, Alex C.; Intorcia, Anthony; Saxon-Labelle, Megan; Pullen, Joel; Scroggins, Alexander; Filon, Jessica; Scott, Sarah; Hoffman, Brittany; Garcia, Angelica; Caviness, John N.; Hentz, Joseph G.; Driver-Dunckley, Erika; Jacobson, Sandra A.; Davis, Kathryn J.; Belden, Christine M.; Long, Kathy E.; Malek-Ahmadi, Michael; Powell, Jessica J.; Gale, Lisa D.; Nicholson, Lisa R.; Caselli, Richard J.; Woodruff, Bryan K.; Rapscak, Steven Z.; Ahern, Geoffrey L.; Shi, Jiong; Burke, Anna D.; Reiman, Eric M.; Sabbagh, Marwan N.

2015-01-01

The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain-only donations and currently has banked more than 1600 brains. More than 430 whole-body donations have been received since this service was commenced in 2005. The collective academic output of the BBDP is now described as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are enrolled as cognitively normal volunteers residing in the retirement communities of metropolitan Phoenix, Arizona. Specific recruitment efforts are also directed at subjects with Alzheimer’s disease, Parkinson’s disease and cancer. The median age at death is 82. Subjects receive standardized general medical, neurological, neuropsychological and movement disorders assessments during life and more than 90% receive full pathological examinations by medically licensed pathologists after death. The Program has been funded through a combination of internal, federal and state of Arizona grants as well as user fees and pharmaceutical industry collaborations. Subsets of the Program are utilized by the US National Institute on Aging Arizona Alzheimer’s Disease Core Center and the US National Institute of Neurological Disorders and Stroke National Brain and Tissue Resource for Parkinson’s Disease and Related Disorders. Substantial funding has also been received from the Michael J. Fox Foundation for Parkinson’s Research. The Program has made rapid autopsy a priority, with a 3.0-hour median postmortem interval for the entire collection. The median RNA Integrity Number (RIN) for frozen brain and body tissue is 8.9 and 7.4, respectively. More than 2500 tissue requests have been served and currently about 200 are served annually. These requests have been made by more than 400 investigators located in 32 US states and 15 countries. Tissue from the BBDP has contributed to more than 350 publications and more than 200 grant-funded projects. PMID:25619230

Pharmacokinetics of pericyte involvement in small-molecular drug transport across the blood-brain barrier.

PubMed

Mihajlica, Nebojsa; Betsholtz, Christer; Hammarlund-Udenaes, Margareta

2018-06-19

Pericytes are perivascular cells that play important roles in the regulation of the blood-brain barrier (BBB) properties. Pericyte-deficiency causes compromised BBB integrity and increase in permeability to different macromolecules mainly by upregulated transcytosis. The aim of the present study was to investigate pericyte involvement in the extent of small-molecular drug transport across the BBB. This was performed with five compounds: diazepam, digoxin, levofloxacin, oxycodone and paliperidone. Compounds were administered at low doses via subcutaneous injections as a cassette (simultaneously) to pericyte-deficient Pdgfb ret/ret mice and corresponding WT controls. Total drug partitioning across the BBB was calculated as the ratio of total drug exposures in brain tissue and plasma (K p,brain ). In addition, equilibrium dialysis experiments were performed to estimate unbound drug fractions in brain (f u,brain ) and plasma (f u,plasma ). This enabled estimation of unbound drug partitioning coefficients (K p,uu,brain ). The results indicated slight tendencies towards increase of total brain exposures in Pdgfb ret/ret mice as reflected in K p,brain values, which were within the 2-fold limit. Part of these differences could be explained by differences in plasma protein binding. No difference was found in brain tissue binding. The combined in vivo and in vitro data resulted in no differences in BBB transport in pericyte-deficiency, as described by similar K p,uu,brain values in Pdgfb ret/ret and control mice. In conclusion, these findings imply no influence of pericytes on the extent of BBB transport of small-molecular drugs, and suggest preserved BBB features relevant for handling of this type of molecules irrespective of pericyte presence at the brain endothelium. Copyright © 2018. Published by Elsevier B.V.

A New Antigen Retrieval Technique for Human Brain Tissue

PubMed Central

Byne, William; Haroutunian, Vahram; García-Villanueva, Mercedes; Rábano, Alberto; García-Amado, María; Prensa, Lucía; Giménez-Amaya, José Manuel

2008-01-01

Immunohistochemical staining of tissues is a powerful tool used to delineate the presence or absence of an antigen. During the last 30 years, antigen visualization in human brain tissue has been significantly limited by the masking effect of fixatives. In the present study, we have used a new method for antigen retrieval in formalin-fixed human brain tissue and examined the effectiveness of this protocol to reveal masked antigens in tissues with both short and long formalin fixation times. This new method, which is based on the use of citraconic acid, has not been previously utilized in brain tissue although it has been employed in various other tissues such as tonsil, ovary, skin, lymph node, stomach, breast, colon, lung and thymus. Thus, we reported here a novel method to carry out immunohistochemical studies in free-floating human brain sections. Since fixation of brain tissue specimens in formaldehyde is a commonly method used in brain banks, this new antigen retrieval method could facilitate immunohistochemical studies of brains with prolonged formalin fixation times. PMID:18852880

Functional MRI registration with tissue-specific patch-based functional correlation tensors.

PubMed

Zhou, Yujia; Zhang, Han; Zhang, Lichi; Cao, Xiaohuan; Yang, Ru; Feng, Qianjin; Yap, Pew-Thian; Shen, Dinggang

2018-06-01

Population studies of brain function with resting-state functional magnetic resonance imaging (rs-fMRI) rely on accurate intersubject registration of functional areas. This is typically achieved through registration using high-resolution structural images with more spatial details and better tissue contrast. However, accumulating evidence has suggested that such strategy cannot align functional regions well because functional areas are not necessarily consistent with anatomical structures. To alleviate this problem, a number of registration algorithms based directly on rs-fMRI data have been developed, most of which utilize functional connectivity (FC) features for registration. However, most of these methods usually extract functional features only from the thin and highly curved cortical grey matter (GM), posing great challenges to accurate estimation of whole-brain deformation fields. In this article, we demonstrate that additional useful functional features can also be extracted from the whole brain, not restricted to the GM, particularly the white-matter (WM), for improving the overall functional registration. Specifically, we quantify local anisotropic correlation patterns of the blood oxygenation level-dependent (BOLD) signals using tissue-specific patch-based functional correlation tensors (ts-PFCTs) in both GM and WM. Functional registration is then performed by integrating the features from different tissues using the multi-channel large deformation diffeomorphic metric mapping (mLDDMM) algorithm. Experimental results show that our method achieves superior functional registration performance, compared with conventional registration methods. © 2018 Wiley Periodicals, Inc.

Determination of Death: A Scientific Perspective on Biological Integration

PubMed Central

Condic, Maureen L.

2016-01-01

Human life is operationally defined by the onset and cessation of organismal function. At postnatal stages of life, organismal integration critically and uniquely requires a functioning brain. In this article, a distinction is drawn between integrated and coordinated biologic activities. While communication between cells can provide a coordinated biologic response to specific signals, it does not support the integrated function that is characteristic of a living human being. Determining the loss of integrated function can be complicated by medical interventions (i.e., “life support”) that uncouple elements of the natural biologic hierarchy underlying our intuitive understanding of death. Such medical interventions can allow living human beings who are no longer able to function in an integrated manner to be maintained in a living state. In contrast, medical intervention can also allow the cells and tissues of an individual who has died to be maintained in a living state. To distinguish between a living human being and living human cells, two criteria are proposed: either the persistence of any form of brain function or the persistence of autonomous integration of vital functions. Either of these criteria is sufficient to determine a human being is alive. PMID:27075193

Accurate and robust brain image alignment using boundary-based registration.

PubMed

Greve, Douglas N; Fischl, Bruce

2009-10-15

The fine spatial scales of the structures in the human brain represent an enormous challenge to the successful integration of information from different images for both within- and between-subject analysis. While many algorithms to register image pairs from the same subject exist, visual inspection shows that their accuracy and robustness to be suspect, particularly when there are strong intensity gradients and/or only part of the brain is imaged. This paper introduces a new algorithm called Boundary-Based Registration, or BBR. The novelty of BBR is that it treats the two images very differently. The reference image must be of sufficient resolution and quality to extract surfaces that separate tissue types. The input image is then aligned to the reference by maximizing the intensity gradient across tissue boundaries. Several lower quality images can be aligned through their alignment with the reference. Visual inspection and fMRI results show that BBR is more accurate than correlation ratio or normalized mutual information and is considerably more robust to even strong intensity inhomogeneities. BBR also excels at aligning partial-brain images to whole-brain images, a domain in which existing registration algorithms frequently fail. Even in the limit of registering a single slice, we show the BBR results to be robust and accurate.

PREDICT: Pattern Representation and Evaluation of Data Through Integration, Correlation and Transformation

DTIC Science & Technology

2015-02-01

SB, Helbok R, et al. Cerebral perfusion pressure thresholds for brain tissue hypoxia and metabolic crisis after poor-grade subarachnoid hemorrhage...for future work. ALARMSMONITORINGDETAILED STATUS HOME Dove, J Doe, Joe Johnson, P. Myers, S Palli, H.Doe, E WBC Platelet Creatinine Lactic Acid AST

Brain abnormalities in cognition, anxiety, and depression regulatory regions in adolescents with single ventricle heart disease.

PubMed

Pike, Nancy A; Roy, Bhaswati; Gupta, Ritika; Singh, Sadhana; Woo, Mary A; Halnon, Nancy J; Lewis, Alan B; Kumar, Rajesh

2018-06-01

Single ventricle heart disease (SVHD) adolescents show cognitive impairments and anxiety and depressive symptoms, indicating the possibility of brain injury in regions that control these functions. However, brain tissue integrity in cognition, anxiety, and depression regulatory sites in SVHD remains unclear. We examined brain tissue changes in SVHD compared to controls using T2-relaxometry procedures, which measure free water content and show tissue injury. Proton-density and T2-weighted images, using a 3.0-Tesla MRI, as well as anxiety (Beck anxiety inventory [BAI]), depressive symptoms (patient health questionnaire-9 [PHQ-9]), and cognition (wide range assessment of memory and learning 2 [WRAML2] and Montreal cognitive assessment [MoCA]) data were collected from 20 SVHD (age: 15.8 ± 1.1 years, male/female: 11/9) and 36 controls (age: 16.0 ± 1.1 years, male/female: 19/17). Whole-brain T2-relaxation maps were calculated, normalized to a common space, smoothed, and compared between groups and sexes (analysis of covariance; covariates: age, sex; p < 0.001). SVHD subjects showed significantly increased BAI and PHQ-9 and reduced MoCA and WRAML2 scores over controls. Several brain regions in SVHD showed increased T2-relaxation values (chronic injury), including the cingulate, and insula, hippocampus/para-hippocampal gyrus, thalamus, hypothalamus, amygdala, frontal white matter, corpus callosum, brainstem, and cerebellar areas. Decreased T2-relaxation values (acute injury) emerged in a few regions, including the prefrontal and cerebellar cortices in SVHD over controls. In addition, male SVHD showed more brain changes over female SVHD. Adolescents with SVHD showed significant brain injury with variable male-female differences in areas that control cognition, anxiety, and depression, which may contribute to functional deficits found in the condition. © 2018 Wiley Periodicals, Inc.

Isolating dividing neural and brain tumour cells for gene expression profiling.

PubMed

Endaya, Berwini; Cavanagh, Brenton; Alowaidi, Faisal; Walker, Tom; de Pennington, Nicholas; Ng, Jin-Ming A; Lam, Paula Y P; Mackay-Sim, Alan; Neuzil, Jiri; Meedeniya, Adrian C B

2016-01-15

The characterisation of dividing brain cells is fundamental for studies ranging from developmental and stem cell biology, to brain cancers. Whilst there is extensive anatomical data on these dividing cells, limited gene transcription data is available due to technical constraints. We focally isolated dividing cells whilst conserving RNA, from culture, primary neural tissue and xenografted glioma tumours, using a thymidine analogue that enables gene transcription analysis. 5-ethynyl-2-deoxyuridine labels the replicating DNA of dividing cells. Once labelled, cultured cells and tissues were dissociated, fluorescently tagged with a revised click chemistry technique and the dividing cells isolated using fluorescence-assisted cell sorting. RNA was extracted and analysed using real time PCR. Proliferation and maturation related gene expression in neurogenic tissues was demonstrated in acutely and 3 day old labelled cells, respectively. An elevated expression of marker and pathway genes was demonstrated in the dividing cells of xenografted brain tumours, with the non-dividing cells showing relatively low levels of expression. BrdU "immune-labelling", the most frequently used protocol for detecting cell proliferation, causes complete denaturation of RNA, precluding gene transcription analysis. This EdU labelling technique, maintained cell integrity during dissociation, minimized copper exposure during labelling and used a cell isolation protocol that avoided cell lysis, thus conserving RNA. The technique conserves RNA, enabling the definition of cell proliferation-related changes in gene transcription of neural and pathological brain cells in cells harvested immediately after division, or following a period of maturation. Copyright © 2015 Elsevier B.V. All rights reserved.

Drug Delivery to the Ischemic Brain

PubMed Central

Thompson, Brandon J.; Ronaldson, Patrick T.

2014-01-01

Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events inneurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for acute ischemic stroke treatment, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can “rescue” salvageable brain tissue and/or protect BBB integrity during ischemic stroke. One class of drugs that may enable neural cell rescue following cerebral ischemia/reperfusion injury is the HMG-CoA reductase inhibitors (i.e., statins). Understanding potential CNS drug delivery pathways for statins is critical to their utility in ischemic stroke. Here, we review molecular pathways associated with cerebral ischemia and novel approaches for delivering drugs to treat ischemic disease. Specifically, we discuss utility of endogenous BBB drug uptake transporters such as organic anion transporting polypeptides (OATPs/Oatps) and nanotechnology-based carriers for optimization of CNS drug delivery. Overall, this chapter highlights state-of-the-art technologies that may improve pharmacotherapy of cerebral ischemia. PMID:25307217

Brain Death and Human Organismal Integration: A Symposium on the Definition of Death

PubMed Central

Moschella, Melissa

2016-01-01

Does the ability of some brain dead bodies to maintain homeostasis with the help of artificial life support actually imply that those bodies are living human organisms? Or might it be possible that a brain dead body on life support is a mere collection of still-living cells, organs and tissues which can coordinate with one another, but which lack the genuine integration that is the hallmark of a unified human organism as a whole? To foster further study of these difficult and timely questions, a Symposium on the Definition of Death was held at The Catholic University of America in June 2014. The Symposium brought together scholars from a variety of disciplines—law, medicine, biology, philosophy and theology—who all share a commitment to the dead donor rule and to a biological definition of death, but who have differing opinions regarding the validity of neurological criteria for human death. The papers found in this special issue are among the fruits of this Symposium. PMID:27107428

Mannitol Improves Brain Tissue Oxygenation in a Model of Diffuse Traumatic Brain Injury.

PubMed

Schilte, Clotilde; Bouzat, Pierre; Millet, Anne; Boucheix, Perrine; Pernet-Gallay, Karin; Lemasson, Benjamin; Barbier, Emmanuel L; Payen, Jean-François

2015-10-01

Based on evidence supporting a potential relation between posttraumatic brain hypoxia and microcirculatory derangements with cell edema, we investigated the effects of the antiedematous agent mannitol on brain tissue oxygenation in a model of diffuse traumatic brain injury. Experimental study. Neurosciences and physiology laboratories. Adult male Wistar rats. Thirty minutes after diffuse traumatic brain injury (impact-acceleration model), rats were IV administered with either a saline solution (traumatic brain injury-saline group) or 20% mannitol (1 g/kg) (traumatic brain injury-mannitol group). Sham-saline and sham-mannitol groups received no insult. Two series of experiments were conducted 2 hours after traumatic brain injury (or equivalent) to investigate 1) the effect of mannitol on brain edema and oxygenation, using a multiparametric magnetic resonance-based approach (n = 10 rats per group) to measure the apparent diffusion coefficient, tissue oxygen saturation, mean transit time, and blood volume fraction in the cortex and caudoputamen; 2) the effect of mannitol on brain tissue PO2 and on venous oxygen saturation of the superior sagittal sinus (n = 5 rats per group); and 3) the cortical ultrastructural changes after treatment (n = 1 per group, taken from the first experiment). Compared with the sham-saline group, the traumatic brain injury-saline group had significantly lower tissue oxygen saturation, brain tissue PO2, and venous oxygen saturation of the superior sagittal sinus values concomitant with diffuse brain edema. These effects were associated with microcirculatory collapse due to astrocyte swelling. Treatment with mannitol after traumatic brain injury reversed all these effects. In the absence of traumatic brain injury, mannitol had no effect on brain oxygenation. Mean transit time and blood volume fraction were comparable between the four groups of rats. The development of posttraumatic brain edema can limit the oxygen utilization by brain tissue without evidence of brain ischemia. Our findings indicate that an antiedematous agent such as mannitol can improve brain tissue oxygenation, possibly by limiting astrocyte swelling and restoring capillary perfusion.

Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo.

PubMed

Viventi, Jonathan; Kim, Dae-Hyeong; Vigeland, Leif; Frechette, Eric S; Blanco, Justin A; Kim, Yun-Soung; Avrin, Andrew E; Tiruvadi, Vineet R; Hwang, Suk-Won; Vanleer, Ann C; Wulsin, Drausin F; Davis, Kathryn; Gelber, Casey E; Palmer, Larry; Van der Spiegel, Jan; Wu, Jian; Xiao, Jianliang; Huang, Yonggang; Contreras, Diego; Rogers, John A; Litt, Brian

2011-11-13

Arrays of electrodes for recording and stimulating the brain are used throughout clinical medicine and basic neuroscience research, yet are unable to sample large areas of the brain while maintaining high spatial resolution because of the need to individually wire each passive sensor at the electrode-tissue interface. To overcome this constraint, we developed new devices that integrate ultrathin and flexible silicon nanomembrane transistors into the electrode array, enabling new dense arrays of thousands of amplified and multiplexed sensors that are connected using fewer wires. We used this system to record spatial properties of cat brain activity in vivo, including sleep spindles, single-trial visual evoked responses and electrographic seizures. We found that seizures may manifest as recurrent spiral waves that propagate in the neocortex. The developments reported here herald a new generation of diagnostic and therapeutic brain-machine interface devices.

The emergence of Nervennahrung: Nerves, mind and metabolism in the long eighteenth century.

PubMed

Stahnisch, Frank W

2012-06-01

Morphological assumptions concerning the form, structure and internal life of the brain and nervous system profoundly influenced contemporary physiological concepts about nerve actions throughout the 'long eighteenth century'. This article investigates some early theories of mind and metabolism. In a bottom-up fashion, it asks how eighteenth-century theories regarding the physiological actions of the body organs shaped the conceptions of the structure of the brain and nervous tissue themselves. These proposed that a healthy Nervennahrung (the German word for 'nerve nutrition', which might be rendered as brain food in modern English), not only guaranteed the integrity and stability of neuronal structures in the body, but also explained the complex texture of the brain and spinal cord in physiological terms. Eighteenth-century nerve theories already embodied a Leitmotiv of neurology and brain psychiatry from the later nineteenth century: 'Without phosphorus there is no thought!' Copyright © 2011 Elsevier Ltd. All rights reserved.

Fetal Cortical Transplants in Adult Rats Subjected to Experimental Brain Injury

PubMed Central

Soares, Holly; McIntosh, Tracy K.

1991-01-01

Fetal cortical tissue was injected into injured adult rat brains following concussive fluid percussion (FP) brain injury. Rats subjected to moderate FP injury received E16 cortex transplant injections into lesioned motor cortex 2 days, 1 week, 2 weeks, and 4 weeks post injury. Histological assessment of transplant survival and integration was based upon Nissl staining, glial fibrillary acidic protein (GFAP) immunocytochemistry, and staining for acetylcholinesterase. In addition to histological analysis, the ability of the transplants to attenuate neurological motor deficits associated with concussive FP brain injury was also tested. Three subgroups of rats receiving transplant 1 week, 2 weeks, and 4 weeks post injury Were chosen for evaluation of neurological motor function. Fetal cortical tissue injected into the injury site 4 weeks post injury failed to incorporate with injured host brain, did not affect glial scar formation, and exhibited extensive GFAP immunoreactivity. No improvement in neurological motor function was observed in animals receiving transplants 4 weeks post injury. Conversely, transplants injected 2 days, 1 week, or 2 weeks post injury survived, incorporated with host brain, exhibited little GFAP immunoreactivity, and successfully attenuated glial scarring. However, no significant improvement in motor function was observed at the one week or two week time points. The inability of the transplants to attenuate motor function may indicate inappropriate host/transplant interaction. Our results demonstrate that there exists a temporal window in which fetal cortical transplants can attenuate glial scarring as well as be successfully incorporated into host brains following FP injury. PMID:1782253

Brain metastasis detection by resonant Raman optical biopsy method

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; Cheng, Gangge; Zhou, Lixin; Zhang, Chunyuan; Pu, Yang; Li, Zhongwu; Liu, Yulong; Li, Qingbo; Wang, Wei; Alfano, Robert R.

2014-03-01

Resonant Raman (RR) spectroscopy provides an effective way to enhance Raman signal from particular bonds associated with key molecules due to changes on a molecular level. In this study, RR is used for detection of human brain metastases of five kinds of primary organs of lung, breast, kidney, rectal and orbital in ex-vivo. The RR spectra of brain metastases cancerous tissues were measured and compared with those of normal brain tissues and the corresponding primary cancer tissues. The differences of five types of brain metastases tissues in key bio-components of carotene, tryptophan, lactate, alanine and methyl/methylene group were investigated. The SVM-KNN classifier was used to categorize a set of RR spectra data of brain metastasis of lung cancerous tissues from normal brain tissue, yielding diagnostic sensitivity and specificity at 100% and 75%, respectively. The RR spectroscopy may provide new moleculebased optical probe tools for diagnosis and classification of brain metastatic of cancers.

TransOmic analysis of forebrain sections in Sp2 conditional knockout embryonic mice using IR-MALDESI imaging of lipids and LC-MS/MS label-free proteomics

PubMed Central

Loziuk, Philip; Meier, Florian; Johnson, Caroline

2016-01-01

Quantitative methods for detection of biological molecules are needed more than ever before in the emerging age of “omics” and “big data.” Here, we provide an integrated approach for systematic analysis of the “lipidome” in tissue. To test our approach in a biological context, we utilized brain tissue selectively deficient for the transcription factor Specificity Protein 2 (Sp2). Conditional deletion of Sp2 in the mouse cerebral cortex results in developmental deficiencies including disruption of lipid metabolism. Silver (Ag) cationization was implemented for infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) to enhance the ion abundances for olefinic lipids, as these have been linked to regulation by Sp2. Combining Ag-doped and conventional IR-MALDESI imaging, this approach was extended to IR-MALDESI imaging of embryonic mouse brains. Further, our imaging technique was combined with bottom-up shotgun proteomic LC-MS/MS analysis and western blot for comparing Sp2 conditional knockout (Sp2-cKO) and wild-type (WT) cortices of tissue sections. This provided an integrated omics dataset which revealed many specific changes to fundamental cellular processes and biosynthetic pathways. In particular, step-specific altered abundances of nucleotides, lipids, and associated proteins were observed in the cerebral cortices of Sp2-cKO embryos. PMID:26942738

A reversibly sealed, easy access, modular (SEAM) microfluidic architecture to establish in vitro tissue interfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abhyankar, Vinay V.; Wu, Meiye; Koh, Chung -Yan

Microfluidic barrier tissue models have emerged as advanced in vitro tools to explore interactions with external stimuli such as drug candidates, pathogens, or toxins. However, the procedures required to establish and maintain these systems can be challenging to implement for end users, particularly those without significant in-house engineering expertise. Here we present a module-based approach that provides an easy-to-use workflow to establish, maintain, and analyze microscale tissue constructs. Our approach begins with a removable culture insert that is magnetically coupled, decoupled, and transferred between standalone, prefabricated microfluidic modules for simplified cell seeding, culture, and downstream analysis. The modular approach allowsmore » several options for perfusion including standard syringe pumps or integration with a self-contained gravity-fed module for simple cell maintenance. As proof of concept, we establish a culture of primary human microvascular endothelial cells (HMVEC) and report combined surface protein imaging and gene expression after controlled apical stimulation with the bacterial endotoxin lipopolysaccharide (LPS). We also demonstrate the feasibility of incorporating hydrated biomaterial interfaces into the microfluidic architecture by integrating an ultra-thin (< 1 μm), self-assembled hyaluronic acid/peptide amphiphile culture membrane with brain-specific Young’s modulus (~ 1kPa). To highlight the importance of including biomimetic interfaces into microscale models we report multi-tiered readouts from primary rat cortical cells cultured on the self-assembled membrane and compare a panel of mRNA targets with primary brain tissue signatures. As a result, we anticipate that the modular approach and simplified operational workflows presented here will enable a wide range of research groups to incorporate microfluidic barrier tissue models into their work.« less

A reversibly sealed, easy access, modular (SEAM) microfluidic architecture to establish in vitro tissue interfaces

DOE PAGES

Abhyankar, Vinay V.; Wu, Meiye; Koh, Chung -Yan; ...

2016-05-26

Microfluidic barrier tissue models have emerged as advanced in vitro tools to explore interactions with external stimuli such as drug candidates, pathogens, or toxins. However, the procedures required to establish and maintain these systems can be challenging to implement for end users, particularly those without significant in-house engineering expertise. Here we present a module-based approach that provides an easy-to-use workflow to establish, maintain, and analyze microscale tissue constructs. Our approach begins with a removable culture insert that is magnetically coupled, decoupled, and transferred between standalone, prefabricated microfluidic modules for simplified cell seeding, culture, and downstream analysis. The modular approach allowsmore » several options for perfusion including standard syringe pumps or integration with a self-contained gravity-fed module for simple cell maintenance. As proof of concept, we establish a culture of primary human microvascular endothelial cells (HMVEC) and report combined surface protein imaging and gene expression after controlled apical stimulation with the bacterial endotoxin lipopolysaccharide (LPS). We also demonstrate the feasibility of incorporating hydrated biomaterial interfaces into the microfluidic architecture by integrating an ultra-thin (< 1 μm), self-assembled hyaluronic acid/peptide amphiphile culture membrane with brain-specific Young’s modulus (~ 1kPa). To highlight the importance of including biomimetic interfaces into microscale models we report multi-tiered readouts from primary rat cortical cells cultured on the self-assembled membrane and compare a panel of mRNA targets with primary brain tissue signatures. As a result, we anticipate that the modular approach and simplified operational workflows presented here will enable a wide range of research groups to incorporate microfluidic barrier tissue models into their work.« less

Spatial cluster analysis of nanoscopically mapped serotonin receptors for classification of fixed brain tissue

NASA Astrophysics Data System (ADS)

Sams, Michael; Silye, Rene; Göhring, Janett; Muresan, Leila; Schilcher, Kurt; Jacak, Jaroslaw

2014-01-01

We present a cluster spatial analysis method using nanoscopic dSTORM images to determine changes in protein cluster distributions within brain tissue. Such methods are suitable to investigate human brain tissue and will help to achieve a deeper understanding of brain disease along with aiding drug development. Human brain tissue samples are usually treated postmortem via standard fixation protocols, which are established in clinical laboratories. Therefore, our localization microscopy-based method was adapted to characterize protein density and protein cluster localization in samples fixed using different protocols followed by common fluorescent immunohistochemistry techniques. The localization microscopy allows nanoscopic mapping of serotonin 5-HT1A receptor groups within a two-dimensional image of a brain tissue slice. These nanoscopically mapped proteins can be confined to clusters by applying the proposed statistical spatial analysis. Selected features of such clusters were subsequently used to characterize and classify the tissue. Samples were obtained from different types of patients, fixed with different preparation methods, and finally stored in a human tissue bank. To verify the proposed method, samples of a cryopreserved healthy brain have been compared with epitope-retrieved and paraffin-fixed tissues. Furthermore, samples of healthy brain tissues were compared with data obtained from patients suffering from mental illnesses (e.g., major depressive disorder). Our work demonstrates the applicability of localization microscopy and image analysis methods for comparison and classification of human brain tissues at a nanoscopic level. Furthermore, the presented workflow marks a unique technological advance in the characterization of protein distributions in brain tissue sections.

Neurodegeneration from mitochondrial insufficiency: nutrients, stem cells, growth factors, and prospects for brain rebuilding using integrative management.

PubMed

Kidd, Parris M

2005-12-01

Degenerative brain disorders (neurodegeneration) can be frustrating for both conventional and alternative practitioners. A more comprehensive, integrative approach is urgently needed. One emerging focus for intervention is brain energetics. Specifically, mitochondrial insufficiency contributes to the etiopathology of many such disorders. Electron leakages inherent to mitochondrial energetics generate reactive oxygen free radical species that may place the ultimate limit on lifespan. Exogenous toxins, such as mercury and other environmental contaminants, exacerbate mitochondrial electron leakage, hastening their demise and that of their host cells. Studies of the brain in Alzheimer's and other dementias, Down syndrome, stroke, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, Friedreich's ataxia, aging, and constitutive disorders demonstrate impairments of the mitochondrial citric acid cycle and oxidative phosphorylation (OXPHOS) enzymes. Imaging or metabolic assays frequently reveal energetic insufficiency and depleted energy reserve in brain tissue in situ. Orthomolecular nutrients involved in mitochondrial metabolism provide clinical benefit. Among these are the essential minerals and the B vitamin group; vitamins E and K; and the antioxidant and energetic cofactors alpha-lipoic acid (ALA), ubiquinone (coenzyme Q10; CoQ10), and nicotinamide adenine dinucleotide, reduced (NADH). Recent advances in the area of stem cells and growth factors encourage optimism regarding brain regeneration. The trophic nutrients acetyl L-carnitine (ALCAR), glycerophosphocholine (GPC), and phosphatidylserine (PS) provide mitochondrial support and conserve growth factor receptors; all three improved cognition in double-blind trials. The omega-3 fatty acid docosahexaenoic acid (DHA) is enzymatically combined with GPC and PS to form membrane phospholipids for nerve cell expansion. Practical recommendations are presented for integrating these safe and well-tolerated orthomolecular nutrients into a comprehensive dietary supplementation program for brain vitality and productive lifespan.

Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers

PubMed Central

Rempe, Ralf G; Hartz, Anika MS

2016-01-01

Matrix metalloproteinases are versatile endopeptidases with many different functions in the body in health and disease. In the brain, matrix metalloproteinases are critical for tissue formation, neuronal network remodeling, and blood–brain barrier integrity. Many reviews have been published on matrix metalloproteinases before, most of which focus on the two best studied matrix metalloproteinases, the gelatinases MMP-2 and MMP-9, and their role in one or two diseases. In this review, we provide a broad overview of the role various matrix metalloproteinases play in brain disorders. We summarize and review current knowledge and understanding of matrix metalloproteinases in the brain and at the blood–brain barrier in neuroinflammation, multiple sclerosis, cerebral aneurysms, stroke, epilepsy, Alzheimer’s disease, Parkinson’s disease, and brain cancer. We discuss the detrimental effects matrix metalloproteinases can have in these conditions, contributing to blood–brain barrier leakage, neuroinflammation, neurotoxicity, demyelination, tumor angiogenesis, and cancer metastasis. We also discuss the beneficial role matrix metalloproteinases can play in neuroprotection and anti-inflammation. Finally, we address matrix metalloproteinases as potential therapeutic targets. Together, in this comprehensive review, we summarize current understanding and knowledge of matrix metalloproteinases in the brain and at the blood–brain barrier in brain disorders. PMID:27323783

Production rates and turnover of triiodothyronine in rat-developing cerebral cortex and cerebellum. Responses to hypothyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silva, J.E.; Matthews, P.S.

1984-09-01

Local 5'-deiodination of serum thyroxine (T4) is the main source of triiodothyronine (T3) for the brain. Since we noted in previous studies that the cerebral cortex of neonatal rats tolerated marked reductions in serum T4 without biochemical hypothyroidism, we examined the in vivo T4 and T3 metabolism in that tissue and in the cerebellum of euthyroid and hypothyroid 2-wk-old rats. We also assessed the contribution of enhanced tissue T4 to T3 conversion and decreased T3 removal from the tissues to the T3 homeostasis in hypothyroid brain. Congenital and neonatal hypothyroidism was induced by adding methimazole to the drinking water. Serum,more » cerebral cortex (Cx), cerebellum (Cm), liver (L) and kidney (R) concentrations of 125I-T4, 125I-T3(T4), and 131I-T3 were measured at various times after injecting 125I-T4 and 131I-T3. The rate of T3 removal from the tissues was measured after injecting an excess of anti-T3-antibody to rats previously injected with tracer T3. In hypothyroidism, the fractional removal rates and clearances were reduced in all tissues, in cortex and cerebellum by 70%, and in liver and kidney ranging from 30 to 50%. While greater than 80% of the 125I-T3(T4) in the brain tissues of euthyroid rats was locally produced, in hypothyroid cerebral cortex and cerebellum the integrated concentrations of 125I-T3(T4) were 2.7- and 1.5-fold greater than in euthyroid rats.« less

Large field-of-view and depth-specific cortical microvascular imaging underlies regional differences in ischemic brain

NASA Astrophysics Data System (ADS)

Qin, Jia; Shi, Lei; Dziennis, Suzan; Wang, Ruikang K.

2014-02-01

Ability to non-invasively monitor and quantify of blood flow, blood vessel morphology, oxygenation and tissue morphology is important for improved diagnosis, treatment and management of various neurovascular disorders, e.g., stroke. Currently, no imaging technique is available that can satisfactorily extract these parameters from in vivo microcirculatory tissue beds, with large field of view and sufficient resolution at defined depth without any harm to the tissue. In order for more effective therapeutics, we need to determine the area of brain that is damaged but not yet dead after focal ischemia. Here we develop an integrated multi-functional imaging system, in which SDW-LSCI (synchronized dual wavelength laser speckle imaging) is used as a guiding tool for OMAG (optical microangiography) to investigate the fine detail of tissue hemodynamics, such as vessel flow, profile, and flow direction. We determine the utility of the integrated system for serial monitoring afore mentioned parameters in experimental stroke, middle cerebral artery occlusion (MCAO) in mice. For 90 min MCAO, onsite and 24 hours following reperfusion, we use SDW-LSCI to determine distinct flow and oxygenation variations for differentiation of the infarction, peri-infarct, reduced flow and contralateral regions. The blood volumes are quantifiable and distinct in afore mentioned regions. We also demonstrate the behaviors of flow and flow direction in the arterials connected to MCA play important role in the time course of MCAO. These achievements may improve our understanding of vascular involvement under pathologic and physiological conditions, and ultimately facilitate clinical diagnosis, monitoring and therapeutic interventions of neurovascular diseases, such as ischemic stroke.

Cell Membrane Tracking in Living Brain Tissue Using Differential Interference Contrast Microscopy.

PubMed

Lee, John; Kolb, Ilya; Forest, Craig R; Rozell, Christopher J

2018-04-01

Differential interference contrast (DIC) microscopy is widely used for observing unstained biological samples that are otherwise optically transparent. Combining this optical technique with machine vision could enable the automation of many life science experiments; however, identifying relevant features under DIC is challenging. In particular, precise tracking of cell boundaries in a thick ( ) slice of tissue has not previously been accomplished. We present a novel deconvolution algorithm that achieves the state-of-the-art performance at identifying and tracking these membrane locations. Our proposed algorithm is formulated as a regularized least squares optimization that incorporates a filtering mechanism to handle organic tissue interference and a robust edge-sparsity regularizer that integrates dynamic edge tracking capabilities. As a secondary contribution, this paper also describes new community infrastructure in the form of a MATLAB toolbox for accurately simulating DIC microscopy images of in vitro brain slices. Building on existing DIC optics modeling, our simulation framework additionally contributes an accurate representation of interference from organic tissue, neuronal cell-shapes, and tissue motion due to the action of the pipette. This simulator allows us to better understand the image statistics (to improve algorithms), as well as quantitatively test cell segmentation and tracking algorithms in scenarios, where ground truth data is fully known.

Visible light spectral domain optical coherence microscopy system for ex vivo imaging

NASA Astrophysics Data System (ADS)

Lichtenegger, Antonia; Harper, Danielle J.; Augustin, Marco; Eugui, Pablo; Fialová, Stanislava; Woehrer, Adelheid; Hitzenberger, Christoph K.; Baumann, Bernhard

2017-02-01

A visible light spectral domain optical coherence microscopy system operating in the wavelength range of 450-680 nm was developed. The resulting large wavelength range of 230 nm enabled an ultrahigh axial resolution of 0.88μm in tissue. The setup consisted of a Michelson interferometer combined with a homemade spectrometer with a spectral resolution of 0.03 nm. Scanning of 1 x 1 mm2 and 0.5 x 0.5 mm2 areas was performed by an integrated microelectromechanical mirror. After scanning the light beam is focused onto the tissue by a commercial objective with a 10 x magnification, resulting in a transverse resolution of 2 μm . Specification measurements showed that a -89 dB sensitivity with a 24 dB/mm roll-off could be achieved with the system. First of all the capabilities of the system were tested by investigating millimeter paper, tape and the USAF (US Air Force) 1951 resolution test target. Finally cerebral tissues from non-pathological and Alzheimer's disease affected brains were investigated. The results showed that structures, such as white and gray matter, could be distinguished. Furthermore a first effort was made to differentiate Alzheimer's disease from healthy brain tissue.

Ultrasoft microwire neural electrodes improve chronic tissue integration

PubMed Central

Du, Zhanhong Jeff; Kolarcik, Christi L.; Kozai, Takashi D.Y.; Luebben, Silvia D.; Sapp, Shawn A.; Zheng, Xin Sally; Nabity, James A.; Cui, X. Tracy

2017-01-01

Chronically implanted neural multi-electrode arrays (MEA) are an essential technology for recording electrical signals from neurons and/or modulating neural activity through stimulation. However, current MEAs, regardless of the type, elicit an inflammatory response that ultimately leads to device failure. Traditionally, rigid materials like tungsten and silicon have been employed to interface with the relatively soft neural tissue. The large stiffness mismatch is thought to exacerbate the inflammatory response. In order to minimize the disparity between the device and the brain, we fabricated novel ultrasoft electrodes consisting of elastomers and conducting polymers with mechanical properties much more similar to those of brain tissue than previous neural implants. In this study, these ultrasoft microelectrodes were inserted and released using a stainless steel shuttle with polyethyleneglycol (PEG) glue. The implanted microwires showed functionality in acute neural stimulation. When implanted for 1 or 8 weeks, the novel soft implants demonstrated significantly reduced inflammatory tissue response at week 8 compared to tungsten wires of similar dimension and surface chemistry. Furthermore, a higher degree of cell body distortion was found next to the tungsten implants compared to the polymer implants. Our results support the use of these novel ultrasoft electrodes for long term neural implants. PMID:28185910

Implications of Airflow Dynamics and Soft-Tissue Reconstructions for the Heat Exchange Potential of Dinosaur Nasal Passages

NASA Astrophysics Data System (ADS)

Bourke, Jason Michael

This study seeks to restore the internal anatomy within the nasal passages of dinosaurs via the use of comparative anatomical methods along with computational fluid dynamic simulations. Nasal airway descriptions and airflow simulations are described for extant birds, crocodylians, and lizards. These descriptions served as a baseline for airflow within the nasal passages of diapsids. The presence of shared airflow and soft-tissue properties found in the nasal passages of extant diapsids, were used to restore soft tissues within the airways of dinosaurs under the assumption that biologically unfeasible airflow patterns (e.g., lack of air movement in olfactory recess) can serve as signals for missing soft tissues. This methodology was tested on several dinosaur taxa. Restored airways in some taxa revealed the potential presence and likely shape of nasal turbinates. Heat transfer efficiency was tested in two dinosaur species with elaborated nasal passages. Results of that analysis revealed that dinosaur noses were efficient heat exchangers that likely played an integral role in maintaining cephalic thermoregulation. Brain cooling via nasal expansion appears to have been necessary for dinosaurs to have achieved their immense body sizes without overheating their brains.

[First clinical experience with extended planning and navigation in an interventional MRI unit].

PubMed

Moche, M; Schmitgen, A; Schneider, J P; Bublat, M; Schulz, T; Voerkel, C; Trantakis, C; Bennek, J; Kahn, T; Busse, H

2004-07-01

To present an advanced concept for patient-based navigation and to report on our first clinical experience with interventions in the cranium, of soft-tissue structures (breast, liver) and in the musculoskeletal system. A PC-based navigation system was integrated into an existing interventional MRI environment. Intraoperatively acquired 3D data were used for interventional planning. The information content of these reference data was increased by integration of additional image modalities (e. g., fMRI, CT) and by color display of areas with early contrast media enhancement. Within 18 months, the system was used in 123 patients undergoing interventions in different anatomic regions (brain: 64, paranasal sinus: 9, breast: 20, liver: 17, bone: 9, muscle: 4). The mean duration of 64 brain interventions was compared with that of 36 procedures using the scanner's standard navigation. In contrast with the continuous scanning mode of the MR system (0.25 fps), the higher quality as well as the real time display (4 fps) of the MR images reconstructed from the 3D reference data allowed adequate hand-eye coordination. With our system, patient movement and tissue shifts could be immediately detected intraoperatively, and, in contrast to the standard procedure, navigation safely resumed after updating the reference data. The navigation system was characterized by good stability, efficient system integration and easy usability. Despite additional working steps still to be optimized, the duration of the image-guided brain tumor resections was not significantly longer. The presented system combines the advantage of intraoperative MRI with established visualization, planning, and real time capabilities of neuronavigation and can be efficiently applied in a broad range of non-neurosurgical interventions.

Heating and eating: brown adipose tissue thermogenesis precedes food ingestion as part of the ultradian basic rest-activity cycle in rats.

PubMed

Blessing, William; Mohammed, Mazher; Ootsuka, Youichirou

2012-02-28

Laboratory rats, throughout the 24 hour day, alternate between behaviorally active and non active episodes that Kleitman called the basic rest-activity cycle (BRAC). We previously demonstrated that brown adipose tissue (BAT), body and brain temperatures and arterial pressure and heart rate increase in an integrated manner during behaviorally active phases. Studies show that eating is preceded by increases in body and brain temperature, but whether eating is integrated into the BRAC has not been investigated. In the present study of chronically instrumented, unrestrained Sprague-Dawley rats, peaks in BAT temperature occurred every 96 ± 7 and 162 ± 16 min (mean ± SE, n=14 rats) in dark and light periods respectively, with no apparent underlying regularity. With food available ad libitum, eating was integrated into the BRAC in a temporally precise manner. Eating occurred only after an increase in BAT temperature, commencing 15 ± 1 min (mean ± SE) after the onset of an increase, with no difference between dark and light phases. There were either no or weak preprandial and postprandial relations between intermeal interval and amount eaten during a given meal. Remarkably, with no food available the rat still disturbed the empty food container 16 ± 1 min (p>0.05 versus ad libitum food) after the onset of increases in BAT temperature, and not at other times. Rather than being triggered by changes in levels of body fuels or other meal-associated factors, in sedentary laboratory rats with ad libitum access to food eating commences as part of the ultradian BRAC, a manifestation of intrinsic brain activity. Copyright © 2011 Elsevier Inc. All rights reserved.

Evans blue dye-enhanced imaging of the brain microvessels using spectral focusing coherent anti-Stokes Raman scattering microscopy

PubMed Central

Lee, Bo-Ram; Joo, Kyung-Il; Choi, Eun Sook; Jahng, Junghoon; Kim, Hyunmin

2017-01-01

We performed dye-enhanced imaging of mouse brain microvessels using spectral focusing coherent anti-Stokes Raman scattering (SF-CARS) microscopy. The resonant signals from C-H stretching in forward CARS usually show high background intensity in tissues, which makes CARS imaging of microvessels difficult. In this study, epi-detection of back-scattered SF-CARS signals showed a negligible background, but the overall intensity of resonant CARS signals was too low to observe the network of brain microvessels. Therefore, Evans blue (EB) dye was used as contrasting agent to enhance the back-scattered SF-CARS signals. Breakdown of brain microvessels by inducing hemorrhage in a mouse was clearly visualized using backward SF-CARS signals, following intravenous injection of EB. The improved visualization of brain microvessels with EB enhanced the sensitivity of SF-CARS, detecting not only the blood vessels themselves but their integrity as well in the brain vasculature. PMID:29049299

Frequency of brain tissue donation for research after suicide.

PubMed

Longaray, Vanessa K; Padoan, Carolina S; Goi, Pedro D; da Fonseca, Rodrigo C; Vieira, Daniel C; Oliveira, Francine H de; Kapczinski, Flávio; Magalhães, Pedro V

2017-01-01

To describe the frequency of brain tissue donation for research purposes by families of individuals that committed suicide. All requests for brain tissue donation to a brain biorepository made to the families of individuals aged 18-60 years who had committed suicide between March 2014 and February 2016 were included. Cases presenting with brain damage due to acute trauma were excluded. Fifty-six cases of suicide were reported. Of these, 24 fulfilled the exclusion criteria, and 11 others were excluded because no next of kin was found to provide informed consent. Of the 21 remaining cases, brain tissue donation was authorized in nine (tissue fragments in seven and the entire organ in two). Donation of brain tissue from suicide cases for research purposes is feasible. The acceptance rate of 42.8% in our sample is in accordance with international data on such donations, and similar to rates reported for neurodegenerative diseases.

Metastasis Infiltration: An Investigation of the Postoperative Brain-Tumor Interface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raore, Bethwel; Schniederjan, Matthew; Prabhu, Roshan

Purpose: This study aims to evaluate brain infiltration of metastatic tumor cells past the main tumor resection margin to assess the biological basis for the use of stereotactic radiosurgery treatment of the tumor resection cavity and visualized resection edge or clinical target volume. Methods and Materials: Resection margin tissue was obtained after gross total resection of a small group of metastatic lesions from a variety of primary sources. The tissue at the border of the tumor and brain tissue was carefully oriented and processed to evaluate the presence of tumor cells within brain tissue and their distance from the resectionmore » margin. Results: Microscopic assessment of the radially oriented tissue samples showed no tumor cells infiltrating the surrounding brain tissue. Among the positive findings were reactive astrocytosis observed on the brain tissue immediately adjacent to the tumor resection bed margin. Conclusions: The lack of evidence of metastatic tumor cell infiltration into surrounding brain suggests the need to target only a narrow depth of the resection cavity margin to minimize normal tissue injury and prevent treatment size-dependent stereotactic radiosurgery complications.« less

Intra-operative visualization of brain tumors with 5-aminolevulinic acid-induced fluorescence.

PubMed

Widhalm, Georg

2014-01-01

Precise histopathological diagnosis of brain tumors is essential for the correct patient management. Furthermore, complete resection of brain tumors is associated with an improved patient prognosis. However, histopathological undergrading and incomplete tumor removal are not uncommon, especially due to insufficient intra-operative visualization of brain tumor tissue. The fluorescent dye 5-aminolevulinic acid (5-ALA) is currently applied for fluorescence-guided resections of high-grade gliomas. The value of 5-ALA-induced protoporphyrin (PpIX) fluorescence for intra-operative visualization of other tumors than high-grade gliomas remains unclear. Within the frame of this thesis, we found a significantly higher rate of complete resections of our high-grade gliomas as compared to control cases by using the newly established 5-ALA fluorescence technology at our department. Additionally, we showed that MRI spectroscopy-based chemical shift imaging (CSI) is capable to identify intratumoral high-grade glioma areas (= anaplastic foci) during navigation guided resections to avoid histopathological undergrading. However, the accuracy of navigation systems with integrated pre-operative imaging data such as CSI declines during resections due to intra-operative brainshift. In two further studies, we found that 5-ALA induced PpIX fluorescence is capable as a novel intra-operative marker to detect anaplastic foci within initially suspected low-grade gliomas independent of brainshift. Finally, we showed that the application of 5-ALA is also of relevance in needle biopsies for intra-operative identification of representative brain tumor tissue. These data indicate that 5-ALA is not only of major importance for resection of high-grade gliomas, but also for intra-operative visualization of anaplastic foci as well as representative brain tumor tissue in needle biopsies unaffected by brainshift. Consequently, this new technique might become a novel standard in brain tumor surgery that optimizes the patient management and improves the patient prognosis by maximizing the extent of tumor resection and enabling a precise histopathological tumor diagnosis.

NMR imaging of cell phone radiation absorption in brain tissue

PubMed Central

Gultekin, David H.; Moeller, Lothar

2013-01-01

A method is described for measuring absorbed electromagnetic energy radiated from cell phone antennae into ex vivo brain tissue. NMR images the 3D thermal dynamics inside ex vivo bovine brain tissue and equivalent gel under exposure to power and irradiation time-varying radio frequency (RF) fields. The absorbed RF energy in brain tissue converts into Joule heat and affects the nuclear magnetic shielding and the Larmor precession. The resultant temperature increase is measured by the resonance frequency shift of hydrogen protons in brain tissue. This proposed application of NMR thermometry offers sufficient spatial and temporal resolution to characterize the hot spots from absorbed cell phone radiation in aqueous media and biological tissues. Specific absorption rate measurements averaged over 1 mg and 10 s in the brain tissue cover the total absorption volume. Reference measurements with fiber optic temperature sensors confirm the accuracy of the NMR thermometry. PMID:23248293

NMR imaging of cell phone radiation absorption in brain tissue.

PubMed

Gultekin, David H; Moeller, Lothar

2013-01-02

A method is described for measuring absorbed electromagnetic energy radiated from cell phone antennae into ex vivo brain tissue. NMR images the 3D thermal dynamics inside ex vivo bovine brain tissue and equivalent gel under exposure to power and irradiation time-varying radio frequency (RF) fields. The absorbed RF energy in brain tissue converts into Joule heat and affects the nuclear magnetic shielding and the Larmor precession. The resultant temperature increase is measured by the resonance frequency shift of hydrogen protons in brain tissue. This proposed application of NMR thermometry offers sufficient spatial and temporal resolution to characterize the hot spots from absorbed cell phone radiation in aqueous media and biological tissues. Specific absorption rate measurements averaged over 1 mg and 10 s in the brain tissue cover the total absorption volume. Reference measurements with fiber optic temperature sensors confirm the accuracy of the NMR thermometry.

Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms.

PubMed

Stewart, Daniel C; Rubiano, Andrés; Dyson, Kyle; Simmons, Chelsey S

2017-01-01

While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17-16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models.

One-Step Optogenetics with Multifunctional Flexible Polymer Fibers

PubMed Central

Park, Seongjun; Guo, Yuanyuan; Jia, Xiaoting; Choe, Han Kyoung; Grena, Benjamin; Kang, Jeewoo; Park, Jiyeon; Lu, Chi; Canales, Andres; Chen, Ritchie; Yim, Yeong Shin; Choi, Gloria B.; Fink, Yoel; Anikeeva, Polina

2017-01-01

Optogenetic interrogation of neural pathways relies on delivery of light-sensitive opsins into tissue and subsequent optical illumination and electrical recording from the regions of interest. Despite the recent development of multifunctional neural probes, integration of these modalities within a single biocompatible platform remains a challenge. Here, we introduce a device composed of an optical waveguide, six electrodes, and two microfluidic channels produced via fiber drawing. Our probes facilitated injections of viral vectors carrying opsin genes, while providing collocated neural recording and optical stimulation. The miniature (< 200 μm) footprint and modest weight (<0.5 g) of these probes allowed for multiple implantations into the mouse brain, which enabled opto-electrophysiological investigation of projections from the basolateral amygdala to the medial prefrontal cortex and ventral hippocampus during behavioral experiments. Fabricated solely from polymers and polymer composites, these flexible probes minimized tissue response to achieve chronic multimodal interrogation of brain circuits with high fidelity. PMID:28218915

Dissecting Cell-Type Composition and Activity-Dependent Transcriptional State in Mammalian Brains by Massively Parallel Single-Nucleus RNA-Seq.

PubMed

Hu, Peng; Fabyanic, Emily; Kwon, Deborah Y; Tang, Sheng; Zhou, Zhaolan; Wu, Hao

2017-12-07

Massively parallel single-cell RNA sequencing can precisely resolve cellular diversity in a high-throughput manner at low cost, but unbiased isolation of intact single cells from complex tissues such as adult mammalian brains is challenging. Here, we integrate sucrose-gradient-assisted purification of nuclei with droplet microfluidics to develop a highly scalable single-nucleus RNA-seq approach (sNucDrop-seq), which is free of enzymatic dissociation and nucleus sorting. By profiling ∼18,000 nuclei isolated from cortical tissues of adult mice, we demonstrate that sNucDrop-seq not only accurately reveals neuronal and non-neuronal subtype composition with high sensitivity but also enables in-depth analysis of transient transcriptional states driven by neuronal activity, at single-cell resolution, in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Genome-wide analysis of brain and gonad transcripts reveals changes of key sex reversal-related genes expression and signaling pathways in three stages of Monopterus albus.

PubMed

Chi, Wei; Gao, Yu; Hu, Qing; Guo, Wei; Li, Dapeng

2017-01-01

The natural sex reversal severely affects the sex ratio and thus decreases the productivity of the rice field eel (Monopterus albus). How to understand and manipulate this process is one of the major issues for the rice field eel stocking. So far the genomics and transcriptomics data available for this species are still scarce. Here we provide a comprehensive study of transcriptomes of brain and gonad tissue in three sex stages (female, intersex and male) from the rice field eel to investigate changes in transcriptional level during the sex reversal process. Approximately 195 thousand unigenes were generated and over 44.4 thousand were functionally annotated. Comparative study between stages provided multiple differentially expressed genes in brain and gonad tissue. Overall 4668 genes were found to be of unequal abundance between gonad tissues, far more than that of the brain tissues (59 genes). These genes were enriched in several different signaling pathways. A number of 231 genes were found with different levels in gonad in each stage, with several reproduction-related genes included. A total of 19 candidate genes that could be most related to sex reversal were screened out, part of these genes' expression patterns were validated by RT-qPCR. The expression of spef2, maats1, spag6 and dmc1 were abundant in testis, but was barely detected in females, while the 17β-hsd12, zpsbp3, gal3 and foxn5 were only expressed in ovary. This study investigated the complexity of brain and gonad transcriptomes in three sex stages of the rice field eel. Integrated analysis of different gene expression and changes in signaling pathways, such as PI3K-Akt pathway, provided crucial data for further study of sex transformation mechanisms.

Mechanical properties of porcine brain tissue in vivo and ex vivo estimated by MR elastography.

PubMed

Guertler, Charlotte A; Okamoto, Ruth J; Schmidt, John L; Badachhape, Andrew A; Johnson, Curtis L; Bayly, Philip V

2018-03-01

The mechanical properties of brain tissue in vivo determine the response of the brain to rapid skull acceleration. These properties are thus of great interest to the developers of mathematical models of traumatic brain injury (TBI) or neurosurgical simulations. Animal models provide valuable insight that can improve TBI modeling. In this study we compare estimates of mechanical properties of the Yucatan mini-pig brain in vivo and ex vivo using magnetic resonance elastography (MRE) at multiple frequencies. MRE allows estimations of properties in soft tissue, either in vivo or ex vivo, by imaging harmonic shear wave propagation. Most direct measurements of brain mechanical properties have been performed using samples of brain tissue ex vivo. It has been observed that direct estimates of brain mechanical properties depend on the frequency and amplitude of loading, as well as the time post-mortem and condition of the sample. Using MRE in the same animals at overlapping frequencies, we observe that porcine brain tissue in vivo appears stiffer than porcine brain tissue samples ex vivo at frequencies of 100 Hz and 125 Hz, but measurements show closer agreement at lower frequencies. Copyright © 2018 Elsevier Ltd. All rights reserved.

In vitro 3D regeneration-like growth of human patient brain tissue.

PubMed

Tang-Schomer, M D; Wu, W B; Kaplan, D L; Bookland, M J

2018-05-01

In vitro culture of primary neurons is widely adapted with embryonic but not mature brain tissue. Here, we extended a previously developed bioengineered three-dimensional (3D) embryonic brain tissue model to resected normal patient brain tissue in an attempt to regenerate human neurons in vitro. Single cells and small sized (diameter < 100 μm) spheroids from dissociated brain tissue were seeded into 3D silk fibroin-based scaffolds, with or without collagen or Matrigel, and compared with two-dimensional cultures and scaffold-free suspension cultures. Changes of cell phenotypes (neuronal, astroglial, neural progenitor, and neuroepithelial) were quantified with flow cytometry and analyzed with a new method of statistical analysis specifically designed for percentage comparison. Compared with a complete lack of viable cells in conventional neuronal cell culture condition, supplements of vascular endothelial growth factor-containing pro-endothelial cell condition led to regenerative growth of neurons and astroglial cells from "normal" human brain tissue of epilepsy surgical patients. This process involved delayed expansion of Nestin+ neural progenitor cells, emergence of TUJ1+ immature neurons, and Vimentin+ neuroepithelium-like cell sheet formation in prolonged cultures (14 weeks). Micro-tissue spheroids, but not single cells, supported the brain tissue growth, suggesting importance of preserving native cell-cell interactions. The presence of 3D scaffold, but not hydrogel, allowed for Vimentin+ cell expansion, indicating a different growth mechanism than pluripotent cell-based brain organoid formation. The slow and delayed process implied an origin of quiescent neural precursors in the neocortex tissue. Further optimization of the 3D tissue model with primary human brain cells could provide personalized brain disease models. Copyright © 2018 John Wiley & Sons, Ltd.

TU-G-210-02: TRANS-FUSIMO - An Integrative Approach to Model-Based Treatment Planning of Liver FUS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Preusser, T.

Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such asmore » the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)« less

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats

PubMed Central

Pong, Alice C.; Jugé, Lauriane; Bilston, Lynne E.; Cheng, Shaokoon

2017-01-01

Introduction Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Methods Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Results Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P < 0.001 for both) but there were no significant changes in cranial cross-sectional area (Spearman, P = 0.35), cortical gray matter stiffness (Spearman, P = 0.24) and caudate-putamen (Spearman, P = 0.11) stiffness. No significant changes in the size of brain structures were observed in the controls. Conclusions This study showed that although brain tissue in the adult hydrocephalic rats was severely compressed, their brain tissue stiffness did not change significantly. These results are in contrast with our previous findings in juvenile hydrocephalic rats which had significantly less brain compression (as the brain circumference was able to stretch with the cranium due to the open skull sutures) and had a significant increase in caudate putamen stiffness. These results suggest that change in brain mechanical properties in hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus. PMID:28837671

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

PubMed

Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

2017-01-01

Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P < 0.001 for both) but there were no significant changes in cranial cross-sectional area (Spearman, P = 0.35), cortical gray matter stiffness (Spearman, P = 0.24) and caudate-putamen (Spearman, P = 0.11) stiffness. No significant changes in the size of brain structures were observed in the controls. This study showed that although brain tissue in the adult hydrocephalic rats was severely compressed, their brain tissue stiffness did not change significantly. These results are in contrast with our previous findings in juvenile hydrocephalic rats which had significantly less brain compression (as the brain circumference was able to stretch with the cranium due to the open skull sutures) and had a significant increase in caudate putamen stiffness. These results suggest that change in brain mechanical properties in hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

Optical pathology of human brain metastasis of lung cancer using combined resonance Raman and spatial frequency spectroscopies

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; Pu, Yang; Cheng, Gangge; Zhou, Lixin; Chen, Jun; Zhu, Ke; Alfano, Robert R.

2016-03-01

Raman spectroscopy has become widely used for diagnostic purpose of breast, lung and brain cancers. This report introduced a new approach based on spatial frequency spectra analysis of the underlying tissue structure at different stages of brain tumor. Combined spatial frequency spectroscopy (SFS), Resonance Raman (RR) spectroscopic method is used to discriminate human brain metastasis of lung cancer from normal tissues for the first time. A total number of thirty-one label-free micrographic images of normal and metastatic brain cancer tissues obtained from a confocal micro- Raman spectroscopic system synchronously with examined RR spectra of the corresponding samples were collected from the identical site of tissue. The difference of the randomness of tissue structures between the micrograph images of metastatic brain tumor tissues and normal tissues can be recognized by analyzing spatial frequency. By fitting the distribution of the spatial frequency spectra of human brain tissues as a Gaussian function, the standard deviation, σ, can be obtained, which was used to generate a criterion to differentiate human brain cancerous tissues from the normal ones using Support Vector Machine (SVM) classifier. This SFS-SVM analysis on micrograph images presents good results with sensitivity (85%), specificity (75%) in comparison with gold standard reports of pathology and immunology. The dual-modal advantages of SFS combined with RR spectroscopy method may open a new way in the neuropathology applications.

Impact of Neurodegenerative Diseases on Drug Binding to Brain Tissues: From Animal Models to Human Samples.

PubMed

Ugarte, Ana; Corbacho, David; Aymerich, María S; García-Osta, Ana; Cuadrado-Tejedor, Mar; Oyarzabal, Julen

2018-04-19

Drug efficacy in the central nervous system (CNS) requires an additional step after crossing the blood-brain barrier. Therapeutic agents must reach their targets in the brain to modulate them; thus, the free drug concentration hypothesis is a key parameter for in vivo pharmacology. Here, we report the impact of neurodegeneration (Alzheimer's disease (AD) and Parkinson's disease (PD) compared with healthy controls) on the binding of 10 known drugs to postmortem brain tissues from animal models and humans. Unbound drug fractions, for some drugs, are significantly different between healthy and injured brain tissues (AD or PD). In addition, drugs binding to brain tissues from AD and PD animal models do not always recapitulate their binding to the corresponding human injured brain tissues. These results reveal potentially relevant implications for CNS drug discovery.

A two-beam acoustic system for tissue analysis.

PubMed

Sachs, T D; Janney, C D

1977-03-01

In the 'thermo-acoustic sensing technique' (TAST), a burst of sound, called the 'thermometer' beam is passed through tissue and its transit time is measured. A focused sound field, called the heating field, then warms a small volume in the path of the therometer beam, in proportion to the absorption. Finally, the therometer beam burst is repeated and its transit time subtracted from that of the initial thermometer burst. This difference measures the velocity perturbation in the tissue produced by the heating field. The transit time difference is td = K integral of infinity-infinity IP dchi where K is the instrument constant, I the heating field intensity, and P a perturbation factor which characterizes the tissues. The integration is carried out along the path of the thermometer beam. The perturbation factor is P = (formula: see text) where C is the specific heat, rho the denisty, V the velocity of sound, (formula: see text) the temperature coefficient of velocity and alpha the heating field absorption coefficient which is apparently sensitive to tissue structure and condition. Experiments on a fixed human brain showed an ability to distinguish between various tissue types combined with a spatial resolution of better than 3 mm. Should predictions based on the data and theory prove correct, TAST may become a non-invasive alternative to biopsy.

Time resolved dosimetry of human brain exposed to low frequency pulsed magnetic fields.

PubMed

Paffi, Alessandra; Camera, Francesca; Lucano, Elena; Apollonio, Francesca; Liberti, Micaela

2016-06-21

An accurate dosimetry is a key issue to understanding brain stimulation and related interaction mechanisms with neuronal tissues at the basis of the increasing amount of literature revealing the effects on human brain induced by low-level, low frequency pulsed magnetic fields (PMFs). Most literature on brain dosimetry estimates the maximum E field value reached inside the tissue without considering its time pattern or tissue dispersivity. Nevertheless a time-resolved dosimetry, accounting for dispersive tissues behavior, becomes necessary considering that the threshold for an effect onset may vary depending on the pulse waveform and that tissues may filter the applied stimulatory fields altering the predicted stimulatory waveform's size and shape. In this paper a time-resolved dosimetry has been applied on a realistic brain model exposed to the signal presented in Capone et al (2009 J. Neural Transm. 116 257-65), accounting for the broadband dispersivity of brain tissues up to several kHz, to accurately reconstruct electric field and current density waveforms inside different brain tissues. The results obtained by exposing the Duke's brain model to this PMF signal show that the E peak in the brain is considerably underestimated if a simple monochromatic dosimetry is carried out at the pulse repetition frequency of 75 Hz.

Time resolved dosimetry of human brain exposed to low frequency pulsed magnetic fields

NASA Astrophysics Data System (ADS)

Paffi, Alessandra; Camera, Francesca; Lucano, Elena; Apollonio, Francesca; Liberti, Micaela

2016-06-01

An accurate dosimetry is a key issue to understanding brain stimulation and related interaction mechanisms with neuronal tissues at the basis of the increasing amount of literature revealing the effects on human brain induced by low-level, low frequency pulsed magnetic fields (PMFs). Most literature on brain dosimetry estimates the maximum E field value reached inside the tissue without considering its time pattern or tissue dispersivity. Nevertheless a time-resolved dosimetry, accounting for dispersive tissues behavior, becomes necessary considering that the threshold for an effect onset may vary depending on the pulse waveform and that tissues may filter the applied stimulatory fields altering the predicted stimulatory waveform’s size and shape. In this paper a time-resolved dosimetry has been applied on a realistic brain model exposed to the signal presented in Capone et al (2009 J. Neural Transm. 116 257-65), accounting for the broadband dispersivity of brain tissues up to several kHz, to accurately reconstruct electric field and current density waveforms inside different brain tissues. The results obtained by exposing the Duke’s brain model to this PMF signal show that the E peak in the brain is considerably underestimated if a simple monochromatic dosimetry is carried out at the pulse repetition frequency of 75 Hz.

Temperature-dependent elastic properties of brain tissues measured with the shear wave elastography method.

PubMed

Liu, Yan-Lin; Li, Guo-Yang; He, Ping; Mao, Ze-Qi; Cao, Yanping

2017-01-01

Determining the mechanical properties of brain tissues is essential in such cases as the surgery planning and surgical training using virtual reality based simulators, trauma research and the diagnosis of some diseases that alter the elastic properties of brain tissues. Here, we suggest a protocol to measure the temperature-dependent elastic properties of brain tissues in physiological saline using the shear wave elastography method. Experiments have been conducted on six porcine brains. Our results show that the shear moduli of brain tissues decrease approximately linearly with a slope of -0.041±0.006kPa/°C when the temperature T increases from room temperature (~23°C) to body temperature (~37°C). A case study has been further conducted which shows that the shear moduli are insensitive to the temperature variation when T is in the range of 37 to 43°C and will increase when T is higher than 43°C. With the present experimental setup, temperature-dependent elastic properties of brain tissues can be measured in a simulated physiological environment and a non-destructive manner. Thus the method suggested here offers a unique tool for the mechanical characterization of brain tissues with potential applications in brain biomechanics research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms

PubMed Central

Rubiano, Andrés; Dyson, Kyle; Simmons, Chelsey S.

2017-01-01

While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples. Samples were tested using a custom-built millimeter-scale indenter, and resulting force-displacement data is analyzed to quantify the steady-state modulus of each sample. We have directly quantified the quasi-static mechanical properties of human brain tumors with effective moduli ranging from 0.17–16.06 kPa for various pathologies. Of the readily available and inexpensive animal tissues tested, chicken liver (steady-state modulus 0.44 ± 0.13 kPa) has similar mechanical properties to normal human brain tissue while chicken crassus gizzard muscle (steady-state modulus 3.00 ± 0.65 kPa) has similar mechanical properties to human brain tumors. Other materials frequently used to mimic brain tissue in mechanical tests, like ballistic gel and chicken breast, were found to be significantly stiffer than both normal and diseased brain tissue. We have directly compared quasi-static properties of brain tissue, brain tumors, and common mechanical surrogates, though additional tests would be required to determine more complex constitutive models. PMID:28582392

Abdominal fat distribution and its relationship to brain changes: the differential effects of age on cerebellar structure and function: a cross-sectional, exploratory study

PubMed Central

Raschpichler, Matthias; Straatman, Kees; Schroeter, Matthias Leopold; Arelin, Katrin; Schlögl, Haiko; Fritzsch, Dominik; Mende, Meinhard; Pampel, André; Böttcher, Yvonne; Stumvoll, Michael; Villringer, Arno; Mueller, Karsten

2013-01-01

Objectives To investigate whether the metabolically important visceral adipose tissue (VAT) relates differently to structural and functional brain changes in comparison with body weight measured as body mass index (BMI). Moreover, we aimed to investigate whether these effects change with age. Design Cross-sectional, exploratory. Setting University Clinic, Integrative Research and Treatment Centre. Participants We included 100 (mean BMI=26.0 kg/m², 42 women) out of 202 volunteers randomly invited by the city's registration office, subdivided into two age groups: young-to-mid-age (n=51, 20–45 years of age, mean BMI=24.9, 24 women) versus old (n=49, 65–70 years of age, mean BMI=27.0, 18 women). Main outcome measures VAT, BMI, subcutaneous abdominal adipose tissue, brain structure (grey matter density), functional brain architecture (eigenvector centrality, EC). Results We discovered a loss of cerebellar structure with increasing VAT in the younger participants, most significantly in regions involved in motor processing. This negative correlation disappeared in the elderly. Investigating functional brain architecture showed again inverse VAT–cerebellum correlations, whereas now regions involved in cognitive and emotional processing were significant. Although we detected similar results for EC using BMI, significant age interaction for both brain structure and functional architecture was only found using VAT. Conclusions Visceral adiposity is associated with cerebellar changes of both structure and function, whereas the regions involved contribute to motor, cognitive and emotional processes. Furthermore, these associations seem to be age dependent, with younger adults’ brains being adversely affected. PMID:23355665

Magnetic resonance elastography (MRE) of the human brain: technique, findings and clinical applications

NASA Astrophysics Data System (ADS)

Hiscox, Lucy V.; Johnson, Curtis L.; Barnhill, Eric; McGarry, Matt D. J.; Huston 3rd, John; van Beek, Edwin J. R.; Starr, John M.; Roberts, Neil

2016-12-01

Neurological disorders are one of the most important public health concerns in developed countries. Established brain imaging techniques such as magnetic resonance imaging (MRI) and x-ray computerised tomography (CT) have been essential in the identification and diagnosis of a wide range of disorders, although usually are insufficient in sensitivity for detecting subtle pathological alterations to the brain prior to the onset of clinical symptoms—at a time when prognosis for treatment is more favourable. The mechanical properties of biological tissue provide information related to the strength and integrity of the cellular microstructure. In recent years, mechanical properties of the brain have been visualised and measured non-invasively with magnetic resonance elastography (MRE), a particularly sensitive medical imaging technique that may increase the potential for early diagnosis. This review begins with an introduction to the various methods used for the acquisition and analysis of MRE data. A systematic literature search is then conducted to identify studies that have specifically utilised MRE to investigate the human brain. Through the conversion of MRE-derived measurements to shear stiffness (kPa) and, where possible, the loss tangent (rad), a summary of results for global brain tissue and grey and white matter across studies is provided for healthy participants, as potential baseline values to be used in future clinical investigations. In addition, the extent to which MRE has revealed significant alterations to the brain in patients with neurological disorders is assessed and discussed in terms of known pathophysiology. The review concludes by predicting the trends for future MRE research and applications in neuroscience.

Brief Report: The Role of National Brain and Tissue Banks in Research on Autism and Developmental Disorders.

ERIC Educational Resources Information Center

Zielke, H. Ronald; And Others

1996-01-01

This paper describes the establishment and work of two brain and tissue banks, which collect brain and other tissues from newly deceased individuals with autism and make these tissues available to researchers. Issues in tissue collection are identified, including the importance of advance planning, religious concerns of families, and the need for…

Prediction of brain deformations and risk of traumatic brain injury due to closed-head impact: quantitative analysis of the effects of boundary conditions and brain tissue constitutive model.

PubMed

Wang, Fang; Han, Yong; Wang, Bingyu; Peng, Qian; Huang, Xiaoqun; Miller, Karol; Wittek, Adam

2018-05-12

In this study, we investigate the effects of modelling choices for the brain-skull interface (layers of tissues between the brain and skull that determine boundary conditions for the brain) and the constitutive model of brain parenchyma on the brain responses under violent impact as predicted using computational biomechanics model. We used the head/brain model from Total HUman Model for Safety (THUMS)-extensively validated finite element model of the human body that has been applied in numerous injury biomechanics studies. The computations were conducted using a well-established nonlinear explicit dynamics finite element code LS-DYNA. We employed four approaches for modelling the brain-skull interface and four constitutive models for the brain tissue in the numerical simulations of the experiments on post-mortem human subjects exposed to violent impacts reported in the literature. The brain-skull interface models included direct representation of the brain meninges and cerebrospinal fluid, outer brain surface rigidly attached to the skull, frictionless sliding contact between the brain and skull, and a layer of spring-type cohesive elements between the brain and skull. We considered Ogden hyperviscoelastic, Mooney-Rivlin hyperviscoelastic, neo-Hookean hyperviscoelastic and linear viscoelastic constitutive models of the brain tissue. Our study indicates that the predicted deformations within the brain and related brain injury criteria are strongly affected by both the approach of modelling the brain-skull interface and the constitutive model of the brain parenchyma tissues. The results suggest that accurate prediction of deformations within the brain and risk of brain injury due to violent impact using computational biomechanics models may require representation of the meninges and subarachnoidal space with cerebrospinal fluid in the model and application of hyperviscoelastic (preferably Ogden-type) constitutive model for the brain tissue.

Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats.

PubMed

Zhang, Na; Cheng, Gen-Yang; Liu, Xian-Zhi; Zhang, Feng-Jiang

2014-05-01

To investigate the effect of acute renal ischemia reperfusion on brain tissue. Fourty eight rats were randomly divided into four groups (n=12): sham operation group, 30 min ischemia 60 min reperfusion group, 60 min ischemia 60 min reperfusion group, and 120 min ischemia 60 min reperfusion group. The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors. Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time. The detection at the molecular level showed decreased Bcl-2 expression, increased Bax expression, upregulated expression of NF-κB and its downstream factor COX-2/PGE2. Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

HIV-1 Phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues

PubMed Central

Lamers, Susanna L.; Gray, Rebecca R.; Salemi, Marco; Huysentruyt, Leanne C.; McGrath, Michael

2010-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that 1) HIV-1 is clearly capable of migrating out of the brain, 2) the meninges are the most likely primary transport tissues, and 3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. PMID:21055482

Combined Bisulfite Restriction Analysis for brain tissue identification.

PubMed

Samsuwan, Jarunya; Muangsub, Tachapol; Yanatatsaneejit, Pattamawadee; Mutirangura, Apiwat; Kitkumthorn, Nakarin

2018-05-01

According to the tissue-specific methylation database (doi: 10.1016/j.gene.2014.09.060), methylation at CpG locus cg03096975 in EML2 has been preliminarily proven to be specific to brain tissue. In this study, we enlarged sample size and developed a technique for identifying brain tissue in aged samples. Combined Bisulfite Restriction Analysis-for EML2 (COBRA-EML2) technique was established and validated in various organ samples obtained from 108 autopsies. In addition, this technique was also tested for its reliability, minimal DNA concentration detected, and use in aged samples and in samples obtained from specific brain compartments and spinal cord. COBRA-EML2 displayed 100% sensitivity and specificity for distinguishing brain tissue from other tissues, showed high reliability, was capable of detecting minimal DNA concentration (0.015ng/μl), could be used for identifying brain tissue in aged samples. In summary, COBRA-EML2 is a technique to identify brain tissue. This analysis is useful in criminal cases since it can identify the vital organ tissues from small samples acquired from criminal scenes. The results from this analysis can be counted as a medical and forensic marker supporting criminal investigations, and as one of the evidences in court rulings. Copyright © 2018 Elsevier B.V. All rights reserved.

New Perspectives on Neuroengineering and Neurotechnologies: NSF-DFG Workshop Report.

PubMed

Moritz, Chet T; Ruther, Patrick; Goering, Sara; Stett, Alfred; Ball, Tonio; Burgard, Wolfram; Chudler, Eric H; Rao, Rajesh P N

2016-07-01

To identify and overcome barriers to creating new neurotechnologies capable of restoring both motor and sensory function in individuals with neurological conditions. This report builds upon the outcomes of a joint workshop between the US National Science Foundation and the German Research Foundation on New Perspectives in Neuroengineering and Neurotechnology convened in Arlington, VA, USA, November 13-14, 2014. The participants identified key technological challenges for recording and manipulating neural activity, decoding, and interpreting brain data in the presence of plasticity, and early considerations of ethical and social issues pertinent to the adoption of neurotechnologies. The envisaged progress in neuroengineering requires tightly integrated hardware and signal processing efforts, advances in understanding of physiological adaptations to closed-loop interactions with neural devices, and an open dialog with stakeholders and potential end-users of neurotechnology. The development of new neurotechnologies (e.g., bidirectional brain-computer interfaces) could significantly improve the quality of life of people living with the effects of brain or spinal cord injury, or other neurodegenerative diseases. Focused efforts aimed at overcoming the remaining barriers at the electrode tissue interface, developing implantable hardware with on-board computation, and refining stimulation methods to precisely activate neural tissue will advance both our understanding of brain function and our ability to treat currently intractable disorders of the nervous system.

Lateralized Resting-State Functional Brain Network Organization Changes in Heart Failure

PubMed Central

Park, Bumhee; Roy, Bhaswati; Woo, Mary A.; Palomares, Jose A.; Fonarow, Gregg C.; Harper, Ronald M.; Kumar, Rajesh

2016-01-01

Heart failure (HF) patients show brain injury in autonomic, affective, and cognitive sites, which can change resting-state functional connectivity (FC), potentially altering overall functional brain network organization. However, the status of such connectivity or functional organization is unknown in HF. Determination of that status was the aim here, and we examined region-to-region FC and brain network topological properties across the whole-brain in 27 HF patients compared to 53 controls with resting-state functional MRI procedures. Decreased FC in HF appeared between the caudate and cerebellar regions, olfactory and cerebellar sites, vermis and medial frontal regions, and precentral gyri and cerebellar areas. However, increased FC emerged between the middle frontal gyrus and sensorimotor areas, superior parietal gyrus and orbito/medial frontal regions, inferior temporal gyrus and lingual gyrus/cerebellar lobe/pallidum, fusiform gyrus and superior orbitofrontal gyrus and cerebellar sites, and within vermis and cerebellar areas; these connections were largely in the right hemisphere (p<0.005; 10,000 permutations). The topology of functional integration and specialized characteristics in HF are significantly changed in regions showing altered FC, an outcome which would interfere with brain network organization (p<0.05; 10,000 permutations). Brain dysfunction in HF extends to resting conditions, and autonomic, cognitive, and affective deficits may stem from altered FC and brain network organization that may contribute to higher morbidity and mortality in the condition. Our findings likely result from the prominent axonal and nuclear structural changes reported earlier in HF; protecting neural tissue may improve FC integrity, and thus, increase quality of life and reduce morbidity and mortality. PMID:27203600

A Unified Framework for Brain Segmentation in MR Images

PubMed Central

Yazdani, S.; Yusof, R.; Karimian, A.; Riazi, A. H.; Bennamoun, M.

2015-01-01

Brain MRI segmentation is an important issue for discovering the brain structure and diagnosis of subtle anatomical changes in different brain diseases. However, due to several artifacts brain tissue segmentation remains a challenging task. The aim of this paper is to improve the automatic segmentation of brain into gray matter, white matter, and cerebrospinal fluid in magnetic resonance images (MRI). We proposed an automatic hybrid image segmentation method that integrates the modified statistical expectation-maximization (EM) method and the spatial information combined with support vector machine (SVM). The combined method has more accurate results than what can be achieved with its individual techniques that is demonstrated through experiments on both real data and simulated images. Experiments are carried out on both synthetic and real MRI. The results of proposed technique are evaluated against manual segmentation results and other methods based on real T1-weighted scans from Internet Brain Segmentation Repository (IBSR) and simulated images from BrainWeb. The Kappa index is calculated to assess the performance of the proposed framework relative to the ground truth and expert segmentations. The results demonstrate that the proposed combined method has satisfactory results on both simulated MRI and real brain datasets. PMID:26089978

Human serum albumin nanoparticles modified with apolipoprotein A-I cross the blood-brain barrier and enter the rodent brain.

PubMed

Zensi, Anja; Begley, David; Pontikis, Charles; Legros, Celine; Mihoreanu, Larisa; Büchel, Claudia; Kreuter, Jörg

2010-12-01

Nanoparticles made of human serum albumin (HSA) and modified with apolipoproteins have previously been shown to transport drugs, which normally do not enter the brain, across the blood-brain barrier (BBB). However the precise mechanism by which nanoparticles with different apolipoproteins on their surface can target to the brain, as yet, has not been totally elucidated. In the present study, HSA nanoparticles with covalently bound apolipoprotein A-I (Apo A-I) as a targetor for brain capillary endothelial cells were injected intravenously into SV 129 mice and Wistar rats. The rodents were sacrificed after 15 or 30 min, and their brains were examined by transmission electron microscopy. Apo A-I nanoparticles could be found inside the endothelial cells of brain capillaries as well as within parenchymal brain tissue of both, mice and rats, whereas control particles without Apo A-I on their surface did not cross the BBB during our experiments. The maintenance of tight junction integrity and barrier function during treatment with nanoparticles was demonstrated by perfusion with a fixative containing lanthanum nitrate as an electron dense marker for the permeability of tight junctions.

Dual-labeling with 5-aminolevulinic acid and fluorescein for fluorescence-guided resection of high-grade gliomas: technical note.

PubMed

Suero Molina, Eric; Wölfer, Johannes; Ewelt, Christian; Ehrhardt, André; Brokinkel, Benjamin; Stummer, Walter

2018-02-01

OBJECTIVE Fluorescence guidance with 5-aminolevulinic acid (5-ALA) helps improve resections of malignant gliomas. However, one limitation is the low intensity of blue light for background illumination. Fluorescein has recently been reintroduced into neurosurgery, and novel microscope systems are available for visualizing this fluorochrome, which highlights all perfused tissues but has limited selectivity for tumor detection. Here, the authors investigate a combination of both fluorochromes: 5-ALA for distinguishing tumor and fluorescein for providing tissue fluorescence of adjacent brain tissue. METHODS The authors evaluated 6 patients who harbored cerebral lesions suggestive of high-grade glioma. Patients received 5-ALA (20 mg/kg) orally 4 hours before induction of anesthesia. Low-dose fluorescein (3 mg/kg intravenous) was injected immediately after anesthesia induction. Pentero microscopes (equipped either with Yellow 560 or Blue 400 filters) were used to visualize fluorescence. To simultaneously visualize both fluorochromes, the Yellow 560 module was combined with external blue light illumination (D-light C System). RESULTS Fluorescein-induced fluorescence created a useful background for protoporphyrin IX (PPIX) fluorescence, which appeared orange to red, surrounded by greenly fluorescent normal brain and edematous tissue. Green brain-tissue fluorescence was helpful in augmenting background. Levels of blue illumination that were too strong obscured PPIX fluorescence. Unspecific extravasation of fluorescein was noted at resection margins, which did not interfere with PPIX fluorescence detection. CONCLUSIONS Dual labeling with both PPIX and fluorescein fluorescence is feasible and gives superior background information during fluorescence-guided resections. The authors believe that this technique carries potential as a next step in fluorescence-guided resections if it is completely integrated into the surgical microscope.

A brain slice bath for physiology and compound microscopy, with dual-sided perifusion.

PubMed

Heyward, P M

2010-12-01

Contemporary in vitro brain slice studies can employ compound microscopes to identify individual neurons or their processes for physiological recording or imaging. This requires that the bath used to maintain the tissue fits within the working distances of a water-dipping objective and microscope condenser. A common means of achieving this is to maintain thin tissue slices on the glass floor of a recording bath, exposing only one surface of the tissue to oxygenated bathing medium. Emerging evidence suggests that physiology can be compromised by this approach. Flowing medium past both sides of submerged brain slices is optimal, but recording baths utilizing this principle are not readily available for use on compound microscopes. This paper describes a tissue bath designed specifically for microscopy and physiological recording, in which temperature-controlled medium flows past both sides of the slices. A particular feature of this design is the use of concentric mesh rings to support and transport the live tissue without mechanical disturbance. The design is also easily adapted for use with thin acute slices, cultured slices, and acutely dispersed or cultured cells maintained either on cover slips or placed directly on the floor of the bath. The low profile of the bath provides a low angle of approach for electrodes, and allows use of standard condensers, nosepieces and water-dipping objective lenses. If visualization of individual neurons is not required, the bath can be mounted on a simple stand and used with a dissecting microscope. Heating is integral to the bath, and any temperature controller capable of driving a resistive load can be used. The bath is robust, readily constructed and requires minimal maintenance. Full construction and operation details are given. © 2010 The Author Journal of Microscopy © 2010 The Royal Microscopical Society.

Robotic multimodality stereotactic brain tissue identification: work in progress

NASA Technical Reports Server (NTRS)

Andrews, R.; Mah, R.; Galvagni, A.; Guerrero, M.; Papasin, R.; Wallace, M.; Winters, J.

1997-01-01

Real-time identification of tissue would improve procedures such as stereotactic brain biopsy (SBX), functional and implantation neurosurgery, and brain tumor excision. To standard SBX equipment has been added: (1) computer-controlled stepper motors to drive the biopsy needle/probe precisely; (2) multiple microprobes to track tissue density, detect blood vessels and changes in blood flow, and distinguish the various tissues being penetrated; (3) neural net learning programs to allow real-time comparisons of current data with a normative data bank; (4) three-dimensional graphic displays to follow the probe as it traverses brain tissue. The probe can differentiate substances such as pig brain, differing consistencies of the 'brain-like' foodstuff tofu, and gels made to simulate brain, as well as detect blood vessels imbedded in these substances. Multimodality probes should improve the safety, efficacy, and diagnostic accuracy of SBX and other neurosurgical procedures.

A family of hyperelastic models for human brain tissue

NASA Astrophysics Data System (ADS)

Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

2017-09-01

Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

Terahertz spectroscopy of brain tissue from a mouse model of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Shi, Lingyan; Shumyatsky, Pavel; Rodríguez-Contreras, Adrián; Alfano, Robert

2016-01-01

The terahertz (THz) absorption and index of refraction of brain tissues from a mouse model of Alzheimer's disease (AD) and a control wild-type (normal) mouse were compared using THz time-domain spectroscopy (THz-TDS). Three dominating absorption peaks associated to torsional-vibrational modes were observed in AD tissue, at about 1.44, 1.8, and 2.114 THz, closer to the peaks of free tryptophan molecules than in normal tissue. A possible reason is that there is more free tryptophan in AD brain tissue, while in normal brain tissue more tryptophan is attached to other molecules. Our study suggests that THz-absorption modes may be used as an AD biomarker fingerprint in brain, and that THz-TDS is a promising technique for early diagnosis of AD.

Direct and efficient transfection of mouse neural stem cells and mature neurons by in vivo mRNA electroporation.

PubMed

Bugeon, Stéphane; de Chevigny, Antoine; Boutin, Camille; Coré, Nathalie; Wild, Stefan; Bosio, Andreas; Cremer, Harold; Beclin, Christophe

2017-11-01

In vivo brain electroporation of DNA expression vectors is a widely used method for lineage and gene function studies in the developing and postnatal brain. However, transfection efficiency of DNA is limited and adult brain tissue is refractory to electroporation. Here, we present a systematic study of mRNA as a vector for acute genetic manipulation in the developing and adult brain. We demonstrate that mRNA electroporation is far more efficient than DNA electroporation, and leads to faster and more homogeneous protein expression in vivo Importantly, mRNA electroporation allows the manipulation of neural stem cells and postmitotic neurons in the adult brain using minimally invasive procedures. Finally, we show that this approach can be efficiently used for functional studies, as exemplified by transient overexpression of the neurogenic factor Myt1l and by stably inactivating Dicer nuclease in vivo in adult born olfactory bulb interneurons and in fully integrated cortical projection neurons. © 2017. Published by The Company of Biologists Ltd.

Harnessing the potential of biomaterials for brain repair after stroke

NASA Astrophysics Data System (ADS)

Tuladhar, Anup; Payne, Samantha L.; Shoichet, Molly S.

2018-03-01

Stroke is a devastating disease for which no clinical treatment exists to regenerate lost tissue. Strategies for brain repair in animal models of stroke include the delivery of drug or cell-based therapeutics; however, the complex anatomy and functional organization of the brain presents many challenges. Biomaterials may alleviate some of these challenges by providing a scaffold, localizing the therapy to the site of action, and/or modulating cues to brain cells. Here, the challenges associated with delivery of therapeutics to the brain and the biomaterial strategies used to overcome these challenges are described. For example, innovative hydrogel delivery systems have been designed to provide sustained trophic factor delivery for endogenous repair and to support transplanted cell survival and integration. Novel treatments, such as electrical stimulation of transplanted cells and the delivery of factors for the direct reprogramming of astrocytes into neurons, may be further enhanced by biomaterial delivery systems. Ultimately, improved clinical translation will be achieved by combining clinically relevant therapies with biomaterials strategies.

Cytokine-mediated blood brain barrier disruption as a conduit for cancer/chemotherapy-associated neurotoxicity and cognitive dysfunction.

PubMed

Wardill, Hannah R; Mander, Kimberley A; Van Sebille, Ysabella Z A; Gibson, Rachel J; Logan, Richard M; Bowen, Joanne M; Sonis, Stephen T

2016-12-15

Neurotoxicity is a common side effect of chemotherapy treatment, with unclear molecular mechanisms. Clinical studies suggest that the most frequent neurotoxic adverse events affect memory and learning, attention, concentration, processing speeds and executive function. Emerging preclinical research points toward direct cellular toxicity and induction of neuroinflammation as key drivers of neurotoxicity and subsequent cognitive impairment. Emerging data now show detectable levels of some chemotherapeutic agents within the CNS, indicating potential disruption of blood brain barrier integrity or transport mechanisms. Blood brain barrier disruption is a key aspect of many neurocognitive disorders, particularly those characterized by a proinflammatory state. Importantly, many proinflammatory mediators able to modulate the blood brain barrier are generated by tissues and organs that are targets for chemotherapy-associated toxicities. This review therefore aims to explore the hypothesis that peripherally derived inflammatory cytokines disrupt blood brain barrier permeability, thereby increasing direct access of chemotherapeutic agents into the CNS to facilitate neuroinflammation and central neurotoxicity. © 2016 UICC.

Effects of Antioxidant N-acetylcysteine Against Paraquat-Induced Oxidative Stress in Vital Tissues of Mice

PubMed Central

Ortiz, Maricelly Santiago; Forti, Kevin Muñoz; Suárez Martinez, Edu B.; Muñoz, Lenin Godoy; Husain, Kazim

2016-01-01

Paraquat (PQ) is a commonly used herbicide that induces oxidative stress via reactive oxygen species (ROS) generation. This study aimed to investigate the effects of the antioxidant N-acetylcysteine (NAC) against PQ-induced oxidative stress in mice. Male Balb/C mice (24) were randomly divided into 4 groups and treated for 3 weeks: 1) control (saline), 2) NAC (0.5% in diet), 3) PQ (20 mg/kg, IP) and 4) combination (PQ + NAC). Afterwards mice were sacrificed and oxidative stress markers were analyzed. Our data showed no significant change in serum antioxidant capacity. PQ enhanced lipid peroxidation (MDA) levels in liver tissue compared to control whereas NAC decreased MDA levels (p<0.05). NAC significantly increased MDA in brain tissue (p<0.05). PQ significantly depleted glutathione (GSH) levels in liver (p=0.001) and brain tissue (p<0.05) but non-significant GSH depletion in lung tissue. NAC counteracted PQ, showing a moderate increase GSH levels in liver and brain tissues. PQ significantly increased 8-oxodeoxyguanosine (8-OH-dG) levels (p<0.05) in liver tissue compared to control without a significant change in brain tissue. NAC treatment ameliorated PQ-induced oxidative DNA damage in the liver tissue. PQ significantly decreased the relative mtDNA amplification and increased the frequency of lesions in liver and brain tissue (p<0.0001), while NAC restored the DNA polymerase activity in liver tissue but not in brain tissue. In conclusion, PQ induced lipid peroxidation, oxidative nuclear DNA and mtDNA damage in liver tissues and depleted liver and brain GSH levels. NAC supplementation ameliorated the PQ-induced oxidative stress response in liver tissue of mice. PMID:27398384

BECon: a tool for interpreting DNA methylation findings from blood in the context of brain.

PubMed

Edgar, R D; Jones, M J; Meaney, M J; Turecki, G; Kobor, M S

2017-08-01

Tissue differences are one of the largest contributors to variability in the human DNA methylome. Despite the tissue-specific nature of DNA methylation, the inaccessibility of human brain samples necessitates the frequent use of surrogate tissues such as blood, in studies of associations between DNA methylation and brain function and health. Results from studies of surrogate tissues in humans are difficult to interpret in this context, as the connection between blood-brain DNA methylation is tenuous and not well-documented. Here, we aimed to provide a resource to the community to aid interpretation of blood-based DNA methylation results in the context of brain tissue. We used paired samples from 16 individuals from three brain regions and whole blood, run on the Illumina 450 K Human Methylation Array to quantify the concordance of DNA methylation between tissues. From these data, we have made available metrics on: the variability of cytosine-phosphate-guanine dinucleotides (CpGs) in our blood and brain samples, the concordance of CpGs between blood and brain, and estimations of how strongly a CpG is affected by cell composition in both blood and brain through the web application BECon (Blood-Brain Epigenetic Concordance; https://redgar598.shinyapps.io/BECon/). We anticipate that BECon will enable biological interpretation of blood-based human DNA methylation results, in the context of brain.

MR OEF imaging in MELAS.

PubMed

Xie, Sheng

2014-01-01

Oxygen extraction fraction (OEF) is defined as the ratio of blood oxygen that a tissue takes from the blood flow to maintain function and morphological integrity. OEF reflects the efficiency of oxygen utilization by the tissue and, therefore, is a hemodynamic measure in brain ischemia. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a common mitochondrial disorder. It is characterized by neurological remissions and relapses and associated with progressive neurocognitive deficits. Because of abnormalities of mitochondrial function in MELAS, defects in the oxidative metabolic pathways of energy production decrease the cerebral oxygen utilization and lead to the reduction of OEF. Quantification of OEF can reflect the functional status of cerebral mitochondria and provide insight into the pathophysiological changes in the brain in MELAS. In light of recent advances in MRI, the discovery of the blood-oxygen level-dependent signal has allowed development of MRI methods targeted toward quantitative OEF imaging. A new MR sequence, termed the gradient-echo sampling of spin echo, was successfully developed to enable quantitative assessment of the OEF in the brain tissue. MR OEF imaging in patients with MELAS detects extensive OEF reduction in the stroke-like lesions, as well as in the normal-appearing brain regions. More severe dysfunction of the mitochondria in the stroke-like lesions was implied at the onset of the stroke-like episode. Determination of OEF throughout the episode demonstrated a chronological change in mitochondrial function in individual cases. Such neuroimaging findings might provide some clues in the investigation of the underlying mechanisms of stroke-like episodes.

Protease-degradable PEG-maleimide coating with on-demand release of IL-1Ra to improve tissue response to neural electrodes

PubMed Central

Gutowski, Stacie M.; Shoemaker, James T.; Templeman, Kellie L.; Wei, Yang; Latour, Robert A.; Bellamkonda, Ravi V.; LaPlaca, Michelle C.; García, Andrés J.

2015-01-01

Neural electrodes are an important part of brain-machine interface devices that can restore functionality to patients with sensory and movement disorders. Chronically implanted neural electrodes induce an unfavorable tissue response which includes inflammation, scar formation, and neuronal cell death, eventually causing loss of electrode function. We developed a poly(ethylene glycol) hydrogel coating for neural electrodes with non-fouling characteristics, incorporated an anti-inflammatory agent, and engineered a stimulus-responsive degradable portion for on-demand release of the anti-inflammatory agent in response to inflammatory stimuli. This coating reduces in vitro glial cell adhesion, cell spreading, and cytokine release compared to uncoated controls. We also analyzed the in vivo tissue response using immunohistochemistry and microarray qRT-PCR. Although no differences were observed among coated and uncoated electrodes for inflammatory cell markers, lower IgG penetration into the tissue around PEG+IL-1Ra coated electrodes indicates an improvement in blood-brain barrier integrity. Gene expression analysis showed higher expression of IL-6 and MMP-2 around PEG+IL-1Ra samples, as well as an increase in CNTF expression, an important marker for neuronal survival. Importantly, increased neuronal survival around coated electrodes compared to uncoated controls was observed. Collectively, these results indicate promising findings for an engineered coating to increase neuronal survival and improve tissue response around implanted neural electrodes. PMID:25617126

Automatic brain tissue segmentation based on graph filter.

PubMed

Kong, Youyong; Chen, Xiaopeng; Wu, Jiasong; Zhang, Pinzheng; Chen, Yang; Shu, Huazhong

2018-05-09

Accurate segmentation of brain tissues from magnetic resonance imaging (MRI) is of significant importance in clinical applications and neuroscience research. Accurate segmentation is challenging due to the tissue heterogeneity, which is caused by noise, bias filed and partial volume effects. To overcome this limitation, this paper presents a novel algorithm for brain tissue segmentation based on supervoxel and graph filter. Firstly, an effective supervoxel method is employed to generate effective supervoxels for the 3D MRI image. Secondly, the supervoxels are classified into different types of tissues based on filtering of graph signals. The performance is evaluated on the BrainWeb 18 dataset and the Internet Brain Segmentation Repository (IBSR) 18 dataset. The proposed method achieves mean dice similarity coefficient (DSC) of 0.94, 0.92 and 0.90 for the segmentation of white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF) for BrainWeb 18 dataset, and mean DSC of 0.85, 0.87 and 0.57 for the segmentation of WM, GM and CSF for IBSR18 dataset. The proposed approach can well discriminate different types of brain tissues from the brain MRI image, which has high potential to be applied for clinical applications.

A novel framework for the local extraction of extra-axial cerebrospinal fluid from MR brain images

NASA Astrophysics Data System (ADS)

Mostapha, Mahmoud; Shen, Mark D.; Kim, SunHyung; Swanson, Meghan; Collins, D. Louis; Fonov, Vladimir; Gerig, Guido; Piven, Joseph; Styner, Martin A.

2018-03-01

The quantification of cerebrospinal fluid (CSF) in the human brain has shown to play an important role in early postnatal brain developmental. Extr a-axial fluid (EA-CSF), which is characterized by the CSF in the subarachnoid space, is promising in the early detection of children at risk for neurodevelopmental disorders. Currently, though, there is no tool to extract local EA-CSF measurements in a way that is suitable for localized analysis. In this paper, we propose a novel framework for the localized, cortical surface based analysis of EA-CSF. In our proposed processing, we combine probabilistic brain tissue segmentation, cortical surface reconstruction as well as streamline based local EA-CSF quantification. For streamline computation, we employ the vector field generated by solving a Laplacian partial differential equation (PDE) between the cortical surface and the outer CSF hull. To achieve sub-voxel accuracy while minimizing numerical errors, fourth-order Runge-Kutta (RK4) integration was used to generate the streamlines. Finally, the local EA-CSF is computed by integrating the CSF probability along the generated streamlines. The proposed local EA-CSF extraction tool was used to study the early postnatal brain development in typically developing infants. The results show that the proposed localized EA-CSF extraction pipeline can produce statistically significant regions that are not observed in previous global approach.

Computational analysis of transcranial magnetic stimulation in the presence of deep brain stimulation probes

NASA Astrophysics Data System (ADS)

Syeda, F.; Holloway, K.; El-Gendy, A. A.; Hadimani, R. L.

2017-05-01

Transcranial Magnetic Stimulation is an emerging non-invasive treatment for depression, Parkinson's disease, and a variety of other neurological disorders. Many Parkinson's patients receive the treatment known as Deep Brain Stimulation, but often require additional therapy for speech and swallowing impairment. Transcranial Magnetic Stimulation has been explored as a possible treatment by stimulating the mouth motor area of the brain. We have calculated induced electric field, magnetic field, and temperature distributions in the brain using finite element analysis and anatomically realistic heterogeneous head models fitted with Deep Brain Stimulation leads. A Figure of 8 coil, current of 5000 A, and frequency of 2.5 kHz are used as simulation parameters. Results suggest that Deep Brain Stimulation leads cause surrounding tissues to experience slightly increased E-field (Δ Emax =30 V/m), but not exceeding the nominal values induced in brain tissue by Transcranial Magnetic Stimulation without leads (215 V/m). The maximum temperature in the brain tissues surrounding leads did not change significantly from the normal human body temperature of 37 °C. Therefore, we ascertain that Transcranial Magnetic Stimulation in the mouth motor area may stimulate brain tissue surrounding Deep Brain Stimulation leads, but will not cause tissue damage.

Long-Term Implanted cOFM Probe Causes Minimal Tissue Reaction in the Brain

PubMed Central

Hochmeister, Sonja; Asslaber, Martin; Kroath, Thomas; Pieber, Thomas R.; Sinner, Frank

2014-01-01

This study investigated the histological tissue reaction to long-term implanted cerebral open flow microperfusion (cOFM) probes in the frontal lobe of the rat brain. Most probe-based cerebral fluid sampling techniques are limited in application time due to the formation of a glial scar that hinders substance exchange between brain tissue and the probe. A glial scar not only functions as a diffusion barrier but also alters metabolism and signaling in extracellular brain fluid. cOFM is a recently developed probe-based technique to continuously sample extracellular brain fluid with an intact blood-brain barrier. After probe implantation, a 2 week healing period is needed for blood-brain barrier reestablishment. Therefore, cOFM probes need to stay in place and functional for at least 15 days after implantation to ensure functionality. Probe design and probe materials are optimized to evoke minimal tissue reaction even after a long implantation period. Qualitative and quantitative histological tissue analysis revealed no continuous glial scar formation around the cOFM probe 30 days after implantation and only a minor tissue reaction regardless of perfusion of the probe. PMID:24621608

HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues.

PubMed

Lamers, Susanna L; Gray, Rebecca R; Salemi, Marco; Huysentruyt, Leanne C; McGrath, Michael S

2011-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that (1) HIV-1 is clearly capable of migrating out of the brain, (2) the meninges are the most likely primary transport tissues, and (3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

Effect of Ginkgo biloba extract on apoptosis of brain tissues in rats with acute cerebral infarction and related gene expression.

PubMed

Wu, C; Zhao, X; Zhang, X; Liu, S; Zhao, H; Chen, Y

2015-06-11

We investigated the effect of Ginkgo biloba extract on apoptosis of brain tissues in rats with acute cerebral infarction and apoptosis-related gene expression. Rat models of acute cerebral infarction were constructed using the suture method, and randomly divided into the control group, model, and treatment groups. In the treatment group, 4 mg/kg G. biloba extract was intravenously injected into the rat tail vein. Phosphate-buffered saline solution was injected in the model group. Seventy-two hours after treatment, rats were euthanized, and brain tissues were removed to analyze the changes in caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) mRNA and protein levels, and variation in brain tissue cells' apoptosis indices was measured. Compared with the control group, the model and treatment groups showed significantly upregulated caspase-3, Bcl-2, and Bax mRNA and protein levels in brain tissues, but remarkably downregulated Bcl-2 mRNA and protein levels (P < 0.05). After treatment, in treatment group brain tissues, caspase-3 and Bax mRNA and protein levels were significantly lower than those in the model group, while Bcl-2 mRNA and protein levels were higher than that in the model group (P < 0.05). The model and treatment groups showed increased cell apoptosis indices of brain tissues compared to the control group; after treatment, the apoptosis index in the treatment group was significantly downregulated compared with that in the model group (P < 0.05). In conclusion, G. biloba extract significantly reduced apoptosis in rat brain tissue cells with acute cerebral infarction and thus protected brain tissues.

Photodynamic diagnosis and related optical techniques for the management of malignant glioma

NASA Astrophysics Data System (ADS)

Sroka, R.; Stepp, H.; Beyer, W.; Markwardt, N.; Rühm, A.

2017-04-01

Malignant gliomas are a devastating brain tumor disease with very poor prognosis. Stereotactic biopsy sampling is routinely used in larger neurosurgical centers to confirm the diagnosis of a suspected brain tumor. This procedure is associated with risk of blood vessel rupture as well as false-negative results. Recent investigations suggest a potential of light-based techniques to improve both therapy and diagnosis of GBM. Optical guidance can be utilized to improve the biopsy sampling procedure in terms of safety, reliability, and efficacy. Recording of optical signals (transmission, remission, fluorescence) can be potentially integrated into a biopsy needle for providing optical detection of tumor tissue and blood vessel recognition during the biopsy sampling. Optical signals can also be used for monitoring purposes during photodynamic therapy. Here, fluorescence signals recorded before the treatment indicate the presence and accumulation level of photosensitizer, while photobleaching of the photosensitizer fluorescence during the treatment can be used as a measure of the effectiveness of the therapy. Finally, transmitted light can reveal problematic tissue-optical conditions as well as changes of the optical properties of the treated tissue, which may be relevant with regard to treatment prognosis and strategy. Different optical concepts for interstitial PDT monitoring and optical tissue property assessment are presented.

Organ-specific physiological responses to acute physical exercise and long-term training in humans.

PubMed

Heinonen, Ilkka; Kalliokoski, Kari K; Hannukainen, Jarna C; Duncker, Dirk J; Nuutila, Pirjo; Knuuti, Juhani

2014-11-01

Virtually all tissues in the human body rely on aerobic metabolism for energy production and are therefore critically dependent on continuous supply of oxygen. Oxygen is provided by blood flow, and, in essence, changes in organ perfusion are also closely associated with alterations in tissue metabolism. In response to acute exercise, blood flow is markedly increased in contracting skeletal muscles and myocardium, but perfusion in other organs (brain and bone) is only slightly enhanced or is even reduced (visceral organs). Despite largely unchanged metabolism and perfusion, repeated exposures to altered hemodynamics and hormonal milieu produced by acute exercise, long-term exercise training appears to be capable of inducing effects also in tissues other than muscles that may yield health benefits. However, the physiological adaptations and driving-force mechanisms in organs such as brain, liver, pancreas, gut, bone, and adipose tissue, remain largely obscure in humans. Along these lines, this review integrates current information on physiological responses to acute exercise and to long-term physical training in major metabolically active human organs. Knowledge is mostly provided based on the state-of-the-art, noninvasive human imaging studies, and directions for future novel research are proposed throughout the review. ©2014 Int. Union Physiol. Sci./Am. Physiol. Soc.

Mechanical properties of the in vivo adolescent human brain.

PubMed

McIlvain, Grace; Schwarb, Hillary; Cohen, Neal J; Telzer, Eva H; Johnson, Curtis L

2018-06-10

Viscoelastic mechanical properties of the in vivo human brain, measured noninvasively with magnetic resonance elastography (MRE), have recently been shown to be affected by aging and neurological disease, as well as relate to performance on cognitive tasks in adults. The demonstrated sensitivity of brain mechanical properties to neural tissue integrity make them an attractive target for examining the developing brain; however, to date, MRE studies on children are lacking. In this work, we characterized global and regional brain stiffness and damping ratio in a sample of 40 adolescents aged 12-14 years, including the lobes of the cerebrum and subcortical gray matter structures. We also compared the properties of the adolescent brain to the healthy adult brain. Temporal and parietal cerebral lobes were softer in adolescents compared to adults. We found that of subcortical gray matter structures, the caudate and the putamen were significantly stiffer in adolescents, and that the hippocampus and amygdala were significantly less stiff than all other subcortical structures. This study provides the first detailed characterization of adolescent brain viscoelasticity and provides baseline data to be used in studying development and pathophysiology. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Identification of the boundary between normal brain tissue and ischemia region using two-photon excitation fluorescence microscopy

NASA Astrophysics Data System (ADS)

Du, Huiping; Wang, Shu; Wang, Xingfu; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

2016-10-01

Ischemic stroke is one of the common neurological diseases, and it is becoming the leading causes of death and permanent disability around the world. Early and accurate identification of the potentially salvageable boundary region of ischemia brain tissues may enable selection of the most appropriate candidates for early stroke therapies. In this work, TPEF microscopy was used to image the microstructures of normal brain tissues, ischemia regions and the boundary region between normal and ischemia brain tissues. The ischemia brain tissues from Sprague-Dawley (SD) rats were subjected to 6 hours of middle cerebral artery occlusion (MCAO). Our study demonstrates that TPEF microscopy has the ability to not only reveal the morphological changes of the neurons but also identify the boundary between normal brain tissue and ischemia region, which correspond well to the hematoxylin and eosin (H and E) stained images. With the development of miniaturized TPEF microscope imaging devices, TPEF microscopy can be developed into an effectively diagnostic and monitoring tool for cerebral ischemia.

Novel Platform for MRI-Guided Convection-Enhanced Delivery of Therapeutics: Preclinical Validation in Nonhuman Primate Brain

PubMed Central

Richardson, R. Mark; Kells, Adrian P.; Martin, Alastair J.; Larson, Paul S.; Starr, Philip A.; Piferi, Peter G.; Bates, Geoffrey; Tansey, Lisa; Rosenbluth, Kathryn H.; Bringas, John R.; Berger, Mitchel S.; Bankiewicz, Krystof S.

2011-01-01

Background/Aims A skull-mounted aiming device and integrated software platform has been developed for MRI-guided neurological interventions. In anticipation of upcoming gene therapy clinical trials, we adapted this device for real-time convection-enhanced delivery of therapeutics via a custom-designed infusion cannula. The targeting accuracy of this delivery system and the performance of the infusion cannula were validated in nonhuman primates. Methods Infusions of gadoteridol were delivered to multiple brain targets and the targeting error was determined for each cannula placement. Cannula performance was assessed by analyzing gadoteridol distributions and by histological analysis of tissue damage. Results The average targeting error for all targets (n = 11) was 0.8 mm (95% CI = 0.14). For clinically relevant volumes, the distribution volume of gadoteridol increased as a linear function (R2 = 0.97) of the infusion volume (average slope = 3.30, 95% CI = 0.2). No infusions in any target produced occlusion, cannula reflux or leakage from adjacent tracts, and no signs of unexpected tissue damage were observed. Conclusions This integrated delivery platform allows real-time convection-enhanced delivery to be performed with a high level of precision, predictability and safety. This approach may improve the success rate for clinical trials involving intracerebral drug delivery by direct infusion. PMID:21494065

Optically enhanced blood-brain-barrier crossing of plasmonic-active nanoparticles in preclinical brain tumor animal models

NASA Astrophysics Data System (ADS)

Yuan, Hsiangkuo; Wilson, Christy M.; Li, Shuqin; Fales, Andrew M.; Liu, Yang; Grant, Gerald; Vo-Dinh, Tuan

2014-02-01

Nanotechnology provides tremendous biomedical opportunities for cancer diagnosis, imaging, and therapy. In contrast to conventional chemotherapeutic agents where their actual target delivery cannot be easily imaged, integrating imaging and therapeutic properties into one platform facilitates the understanding of pharmacokinetic profiles, and enables monitoring of the therapeutic process in each individual. Such a concept dubbed "theranostics" potentiates translational research and improves precision medicine. One particular challenging application of theranostics involves imaging and controlled delivery of nanoplatforms across blood-brain-barrier (BBB) into brain tissues. Typically, the BBB hinders paracellular flux of drug molecules into brain parenchyma. BBB disrupting agents (e.g. mannitol, focused ultrasound), however, suffer from poor spatial confinement. It has been a challenge to design a nanoplatform not only acts as a contrast agent but also improves the BBB permeation. In this study, we demonstrated the feasibility of plasmonic gold nanoparticles as both high-resolution optical contrast agent and focalized tumor BBB permeation-inducing agent. We specifically examined the microscopic distribution of nanoparticles in tumor brain animal models. We observed that most nanoparticles accumulated at the tumor periphery or perivascular spaces. Nanoparticles were present in both endothelial cells and interstitial matrices. This study also demonstrated a novel photothermal-induced BBB permeation. Fine-tuning the irradiating energy induced gentle disruption of the vascular integrity, causing short-term extravasation of nanomaterials but without hemorrhage. We conclude that our gold nanoparticles are a powerful biocompatible contrast agent capable of inducing focal BBB permeation, and therefore envision a strong potential of plasmonic gold nanoparticle in future brain tumor imaging and therapy.

Navigating conjugated polymer actuated neural probes in a brain phantom

NASA Astrophysics Data System (ADS)

Daneshvar, Eugene D.; Kipke, Daryl; Smela, Elisabeth

2012-04-01

Neural probe insertion methods have a direct impact on the longevity of the device in the brain. Initial tissue and vascular damage caused by the probe entering the brain triggers a chronic tissue response that is known to attenuate neural recordings and ultimately encapsulate the probes. Smaller devices have been found to evoke reduced inflammatory response. One way to record from undamaged neural networks may be to position the electrode sites away from the probe. To investigate this approach, we are developing probes with controllably movable electrode projections, which would move outside of the zone that is damaged by the insertion of the larger probe. The objective of this study was to test the capability of conjugated polymer bilayer actuators to actuate neural electrode projections from a probe shank into a transparent brain phantom. Parylene neural probe devices, having five electrode projections with actuating segments and with varying widths (50 - 250 μm) and lengths (200 - 1000 μm) were fabricated. The electroactive polymer polypyrrole (PPy) was used to bend or flatten the projections. The devices were inserted into the brain phantom using an electronic microdrive while simultaneously activating the actuators. Deflections were quantified based on video images. The electrode projections were successfully controlled to either remain flat or to actuate out-of-plane and into the brain phantom during insertion. The projection width had a significant effect on their ability to deflect within the phantom, with thinner probes deflecting but not the wider ones. Thus, small integrated conjugated polymer actuators may enable multiple neuro-experiments and applications not possible before.

Diffusion tensor imaging and myelin composition analysis reveal abnormal myelination in corpus callosum of canine mucopolysaccharidosis I

PubMed Central

Provenzale, James M.; Nestrasil, Igor; Chen, Steven; Kan, Shih-hsin; Le, Steven Q.; Jens, Jacqueline K.; Snella, Elizabeth M.; Vondrak, Kristen N.; Yee, Jennifer K.; Vite, Charles H.; Elashoff, David; Duan, Lewei; Wang, Raymond Y.; Ellinwood, N. Matthew; Guzman, Miguel A.; Shapiro, Elsa G.; Dickson, Patricia I.

2015-01-01

Children with mucopolysaccharidosis I (MPS I) develop hyperintense white matter foci on T2-weighted brain magnetic resonance (MR) imaging that are associated clinically with cognitive impairment. We report here a diffusion tensor imaging (DTI) and tissue evaluation of white matter in a canine model of MPS I. We found that two DTI parameters, fractional anisotropy (a measure of white matter integrity) and radial diffusivity (which reflects degree of myelination) were abnormal in the corpus callosum of MPS I dogs compared to carrier controls. Tissue studies of the corpus callosum showed reduced expression of myelin-related genes and an abnormal composition of myelin in MPS I dogs. We treated MPS I dogs with recombinant alpha-l-iduronidase, which is the enzyme that is deficient in MPS I disease. The recombinant alpha-l-iduronidase was administered by intrathecal injection into the cisterna magna. Treated dogs showed partial correction of corpus callosum myelination. Our findings suggest that abnormal myelination occurs in the canine MPS I brain, that it may underlie clinically-relevant brain imaging findings in human MPS I patients, and that it may respond to treatment. PMID:26222335

Postmortem changes in the neuroanatomical characteristics of the primate brain: the hippocampal formation

PubMed Central

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L.; Amaral, David G.

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused, or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger, as compared to perfusion-fixed tissue. Non-phosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well-stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences. PMID:18972553

Postmortem changes in the neuroanatomical characteristics of the primate brain: hippocampal formation.

PubMed

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L; Amaral, David G

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger as compared to perfusion-fixed tissue. Nonphosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells, and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences.

Cortical and subcortical atrophy in Alzheimer disease: parallel atrophy of thalamus and hippocampus.

PubMed

Štěpán-Buksakowska, Irena; Szabó, Nikoletta; Hořínek, Daniel; Tóth, Eszter; Hort, Jakub; Warner, Joshua; Charvát, František; Vécsei, László; Roček, Miloslav; Kincses, Zsigmond T

2014-01-01

Brain atrophy is a key imaging hallmark of Alzheimer disease (AD). In this study, we carried out an integrative evaluation of AD-related atrophy. Twelve patients with AD and 13 healthy controls were enrolled. We conducted a cross-sectional analysis of total brain tissue volumes with SIENAX. Localized gray matter atrophy was identified with optimized voxel-wise morphometry (FSL-VBM), and subcortical atrophy was evaluated by active shape model implemented in FMRIB's Integrated Registration Segmentation Toolkit. SIENAX analysis demonstrated total brain atrophy in AD patients; voxel-based morphometry analysis showed atrophy in the bilateral mediotemporal regions and in the posterior brain regions. In addition, regarding the diminished volumes of thalami and hippocampi in AD patients, subsequent vertex analysis of the segmented structures indicated shrinkage of the bilateral anterior thalami and the left medial hippocampus. Interestingly, the volume of the thalami and hippocampi were highly correlated with the volume of the thalami and amygdalae on both sides in AD patients, but not in healthy controls. This complex structural information proved useful in the detailed interpretation of AD-related neurodegenerative process, as the multilevel approach showed both global and local atrophy on cortical and subcortical levels. Most importantly, our results raise the possibility that subcortical structure atrophy is not independent in AD patients.

Effects of the Variation in Brain Tissue Mechanical Properties on the Intracranial Response of a 6-Year-Old Child.

PubMed

Cui, Shihai; Li, Haiyan; Li, Xiangnan; Ruan, Jesse

2015-01-01

Brain tissue mechanical properties are of importance to investigate child head injury using finite element (FE) method. However, these properties used in child head FE model normally vary in a large range in published literatures because of the insufficient child cadaver experiments. In this work, a head FE model with detailed anatomical structures is developed from the computed tomography (CT) data of a 6-year-old healthy child head. The effects of brain tissue mechanical properties on traumatic brain response are also analyzed by reconstruction of a head impact on engine hood according to Euro-NCAP testing regulation using FE method. The result showed that the variations of brain tissue mechanical parameters in linear viscoelastic constitutive model had different influences on the intracranial response. Furthermore, the opposite trend was obtained in the predicted shear stress and shear strain of brain tissues caused by the variations of mentioned parameters.

Neurosurgical Applications of High-Intensity Focused Ultrasound with Magnetic Resonance Thermometry.

PubMed

Colen, Rivka R; Sahnoune, Iman; Weinberg, Jeffrey S

2017-10-01

Magnetic resonance guided focused ultrasound surgery (MRgFUS) has potential noninvasive effects on targeted tissue. MRgFUS integrates MRI and focused ultrasound surgery (FUS) into a single platform. MRI enables visualization of the target tissue and monitors ultrasound-induced effects in near real-time during FUS treatment. MRgFUS may serve as an adjunct or replace invasive surgery and radiotherapy for specific conditions. Its thermal effects ablate tumors in locations involved in movement disorders and essential tremors. Its nonthermal effects increase blood-brain barrier permeability to enhance delivery of therapeutics and other molecules. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of blood vessels on light distribution in optogenetic stimulation of cortex.

PubMed

Azimipour, Mehdi; Atry, Farid; Pashaie, Ramin

2015-05-15

In this Letter, the impact of blood vessels on light distribution during photostimulation of cortical tissue in small rodents is investigated. Brain optical properties were extracted using a double-integrating sphere setup, and optical coherence tomography was used to image cortical vessels and capillaries to generate a three-dimensional angiogram of the cortex. By combining these two datasets, a complete volumetric structure of the cortical tissue was developed and linked to a Monte Carlo code which simulates light propagation in this inhomogeneous structure and illustrates the effect of blood vessels on the penetration depth and pattern preservation in optogenetic stimulation.

Multimodality Instrument for Tissue Characterization

NASA Technical Reports Server (NTRS)

Mah, Robert W. (Inventor); Andrews, Russell J. (Inventor)

2000-01-01

A system with multimodality instrument for tissue identification includes a computer-controlled motor driven heuristic probe with a multisensory tip is discussed. For neurosurgical applications, the instrument is mounted on a stereotactic frame for the probe to penetrate the brain in a precisely controlled fashion. The resistance of the brain tissue being penetrated is continually monitored by a miniaturized strain gauge attached to the probe tip. Other modality sensors may be mounted near the probe tip to provide real-time tissue characterizations and the ability to detect the proximity of blood vessels, thus eliminating errors normally associated with registration of pre-operative scans, tissue swelling, elastic tissue deformation, human judgement, etc., and rendering surgical procedures safer, more accurate, and efficient. A neural network, program adaptively learns the information on resistance and other characteristic features of normal brain tissue during the surgery and provides near real-time modeling. A fuzzy logic interface to the neural network program incorporates expert medical knowledge in the learning process. Identification of abnormal brain tissue is determined by the detection of change and comparison with previously learned models of abnormal brain tissues. The operation of the instrument is controlled through a user friendly graphical interface. Patient data is presented in a 3D stereographics display. Acoustic feedback of selected information may optionally be provided. Upon detection of the close proximity to blood vessels or abnormal brain tissue, the computer-controlled motor immediately stops probe penetration.

The Importance of Brain Banks for Molecular Neuropathological Research: The New South Wales Tissue Resource Centre Experience

PubMed Central

Dedova, Irina; Harding, Antony; Sheedy, Donna; Garrick, Therese; Sundqvist, Nina; Hunt, Clare; Gillies, Juliette; Harper, Clive G.

2009-01-01

New developments in molecular neuropathology have evoked increased demands for postmortem human brain tissue. The New South Wales Tissue Resource Centre (TRC) at The University of Sydney has grown from a small tissue collection into one of the leading international brain banking facilities, which operates with best practice and quality control protocols. The focus of this tissue collection is on schizophrenia and allied disorders, alcohol use disorders and controls. This review highlights changes in TRC operational procedures dictated by modern neuroscience, and provides examples of applications of modern molecular techniques to study the neuropathogenesis of many different brain disorders. PMID:19333451

Different modes of herpes simplex virus type 1 spread in brain and skin tissues.

PubMed

Tsalenchuck, Yael; Tzur, Tomer; Steiner, Israel; Panet, Amos

2014-02-01

Herpes simplex virus type 1 (HSV-1) initially infects the skin and subsequently spreads to the nervous system. To investigate and compare HSV-1 mode of propagation in the two clinically relevant tissues, we have established ex vivo infection models, using native tissues of mouse and human skin, as well as mouse brain, maintained in organ cultures. HSV-1, which is naturally restricted to the human, infects and spreads in the mouse and human skin tissues in a similar fashion, thus validating the mouse model. The spread of HSV-1 in the skin was concentric to form typical plaques of limited size, predominantly of cytopathic cells. By contrast, HSV-1 spread in the brain tissue was directed along specific neuronal networks with no apparent cytopathic effect. Two additional differences were noted following infection of the skin and brain tissues. First, only a negligible amount of extracellular progeny virus was produced of the infected brain tissues, while substantial quantity of infectious progeny virus was released to the media of the infected skin. Second, antibodies against HSV-1, added following the infection, effectively restricted viral spread in the skin but have no effect on viral spread in the brain tissue. Taken together, these results reveal that HSV-1 spread within the brain tissue mostly by direct transfer from cell to cell, while in the skin the progeny extracellular virus predominates, thus facilitating the infection to new individuals.

Hyperspectral imaging solutions for brain tissue metabolic and hemodynamic monitoring: past, current and future developments

NASA Astrophysics Data System (ADS)

Giannoni, Luca; Lange, Frédéric; Tachtsidis, Ilias

2018-04-01

Hyperspectral imaging (HSI) technologies have been used extensively in medical research, targeting various biological phenomena and multiple tissue types. Their high spectral resolution over a wide range of wavelengths enables acquisition of spatial information corresponding to different light-interacting biological compounds. This review focuses on the application of HSI to monitor brain tissue metabolism and hemodynamics in life sciences. Different approaches involving HSI have been investigated to assess and quantify cerebral activity, mainly focusing on: (1) mapping tissue oxygen delivery through measurement of changes in oxygenated (HbO2) and deoxygenated (HHb) hemoglobin; and (2) the assessment of the cerebral metabolic rate of oxygen (CMRO2) to estimate oxygen consumption by brain tissue. Finally, we introduce future perspectives of HSI of brain metabolism, including its potential use for imaging optical signals from molecules directly involved in cellular energy production. HSI solutions can provide remarkable insight in understanding cerebral tissue metabolism and oxygenation, aiding investigation on brain tissue physiological processes.

A study on the antioxidant effect of Coriolus versicolor polysaccharide in rat brain tissues.

PubMed

Chen, Jiayu; Jin, Xiaoyan; Zhang, Liting; Yang, Linjun

2013-01-01

The objective of the study was to investigate the antioxidant effect of Chinese medicine Coriolus versicolor polysaccharide on brain tissue and its mechanism in rats. SOD, MDA and GSH-Px levels in rat brain tissues were determined with SD rats as the animal model. The results showed that Coriolus versicolor polysaccharide can reduce the lipid peroxidation level in brain tissues during exhaustive exercise in rats, and can accelerate the removal of free radicals. The study concluded that its antioxidant effect is relatively apparent.

Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

NASA Astrophysics Data System (ADS)

Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

2016-03-01

In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

The Relationship of Three-Dimensional Human Skull Motion to Brain Tissue Deformation in Magnetic Resonance Elastography Studies

PubMed Central

Badachhape, Andrew A.; Okamoto, Ruth J.; Durham, Ramona S.; Efron, Brent D.; Nadell, Sam J.; Johnson, Curtis L.; Bayly, Philip V.

2017-01-01

In traumatic brain injury (TBI), membranes such as the dura mater, arachnoid mater, and pia mater play a vital role in transmitting motion from the skull to brain tissue. Magnetic resonance elastography (MRE) is an imaging technique developed for noninvasive estimation of soft tissue material parameters. In MRE, dynamic deformation of brain tissue is induced by skull vibrations during magnetic resonance imaging (MRI); however, skull motion and its mode of transmission to the brain remain largely uncharacterized. In this study, displacements of points in the skull, reconstructed using data from an array of MRI-safe accelerometers, were compared to displacements of neighboring material points in brain tissue, estimated from MRE measurements. Comparison of the relative amplitudes, directions, and temporal phases of harmonic motion in the skulls and brains of six human subjects shows that the skull–brain interface significantly attenuates and delays transmission of motion from skull to brain. In contrast, in a cylindrical gelatin “phantom,” displacements of the rigid case (reconstructed from accelerometer data) were transmitted to the gelatin inside (estimated from MRE data) with little attenuation or phase lag. This quantitative characterization of the skull–brain interface will be valuable in the parameterization and validation of computer models of TBI. PMID:28267188

The Relationship of Three-Dimensional Human Skull Motion to Brain Tissue Deformation in Magnetic Resonance Elastography Studies.

PubMed

Badachhape, Andrew A; Okamoto, Ruth J; Durham, Ramona S; Efron, Brent D; Nadell, Sam J; Johnson, Curtis L; Bayly, Philip V

2017-05-01

In traumatic brain injury (TBI), membranes such as the dura mater, arachnoid mater, and pia mater play a vital role in transmitting motion from the skull to brain tissue. Magnetic resonance elastography (MRE) is an imaging technique developed for noninvasive estimation of soft tissue material parameters. In MRE, dynamic deformation of brain tissue is induced by skull vibrations during magnetic resonance imaging (MRI); however, skull motion and its mode of transmission to the brain remain largely uncharacterized. In this study, displacements of points in the skull, reconstructed using data from an array of MRI-safe accelerometers, were compared to displacements of neighboring material points in brain tissue, estimated from MRE measurements. Comparison of the relative amplitudes, directions, and temporal phases of harmonic motion in the skulls and brains of six human subjects shows that the skull-brain interface significantly attenuates and delays transmission of motion from skull to brain. In contrast, in a cylindrical gelatin "phantom," displacements of the rigid case (reconstructed from accelerometer data) were transmitted to the gelatin inside (estimated from MRE data) with little attenuation or phase lag. This quantitative characterization of the skull-brain interface will be valuable in the parameterization and validation of computer models of TBI.

Ultrasmall implantable composite microelectrodes with bioactive surfaces for chronic neural interfaces

PubMed Central

Kozai, Takashi D. Yoshida; Langhals, Nicholas B.; Patel, Paras R.; Deng, Xiaopei; Zhang, Huanan; Smith, Karen L.; Lahann, Joerg; Kotov, Nicholas A.; Kipke, Daryl R.

2012-01-01

Implantable neural microelectrodes that can record extracellular biopotentials from small, targeted groups of neurons are critical for neuroscience research and emerging clinical applications including brain-controlled prosthetic devices. The crucial material-dependent problem is developing microelectrodes that record neural activity from the same neurons for years with high fidelity and reliability. Here, we report the development of an integrated composite electrode consisting of a carbon-fibre core, a poly(p-xylylene)-based thin-film coating that acts as a dielectric barrier and that is functionalized to control intrinsic biological processes, and a poly(thiophene)-based recording pad. The resulting implants are an order of magnitude smaller than traditional recording electrodes, and more mechanically compliant with brain tissue. They were found to elicit much reduced chronic reactive tissue responses and enabled single-neuron recording in acute and early chronic experiments in rats. This technology, taking advantage of new composites, makes possible highly selective and stealthy neural interface devices towards realizing long-lasting implants. PMID:23142839

Advanced magnetic resonance imaging methods for planning and monitoring radiation therapy in patients with high-grade glioma.

PubMed

Lupo, Janine M; Nelson, Sarah J

2014-10-01

This review explores how the integration of advanced imaging methods with high-quality anatomical images significantly improves the characterization, target definition, assessment of response to therapy, and overall management of patients with high-grade glioma. Metrics derived from diffusion-, perfusion-, and susceptibility-weighted magnetic resonance imaging in conjunction with magnetic resonance spectroscopic imaging, allows us to characterize regions of edema, hypoxia, increased cellularity, and necrosis within heterogeneous tumor and surrounding brain tissue. Quantification of such measures may provide a more reliable initial representation of tumor delineation and response to therapy than changes in the contrast-enhancing or T2 lesion alone and have a significant effect on targeting resection, planning radiation, and assessing treatment effectiveness. In the long term, implementation of these imaging methodologies can also aid in the identification of recurrent tumor and its differentiation from treatment-related confounds and facilitate the detection of radiationinduced vascular injury in otherwise normal-appearing brain tissue.

Multiphoton fluorescence imaging of NADH to quantify metabolic changes in epileptic tissue in vitro

NASA Astrophysics Data System (ADS)

Chia, Thomas H.; Zinter, Joseph; Spencer, Dennis D.; Williamson, Anne; Levene, Michael J.

2007-02-01

A powerful advantage of multiphoton microscopy is its ability to image endogenous fluorophores such as the ubiquitous coenzyme NADH in discrete cellular populations. NADH is integral in both oxidative and non-oxidative cellular metabolism. NADH loses fluorescence upon oxidation to NAD +; thus changes in NADH fluorescence can be used to monitor metabolism. Recent studies have suggested that hypo metabolic astrocytes play an important role in cases of temporal lobe epilepsy (TLE). Current theories suggest this may be due to defective and/or a reduced number of mitochondria or dysfunction of the neuronal-astrocytic metabolic coupling. Measuring NADH fluorescence changes following chemical stimulation enables the quantification of the cellular distribution of metabolic anomalies in epileptic brain tissue compared to healthy tissue. We present what we believe to be the first multiphoton microscopy images of NADH from the human brain. We also present images of NADH fluorescence from the hippocampus of the kainate-treated rat TLE model. In some experiments, human and rat astrocytes were selectively labeled with the fluorescent dye sulforhodamine 101 (SR101). Our results demonstrate that multiphoton microscopy is a powerful tool for assaying the metabolic pathologies associated with temporal lobe epilepsy in humans and in rodent models.

High-sensitivity terahertz imaging of traumatic brain injury in a rat model

NASA Astrophysics Data System (ADS)

Zhao, Hengli; Wang, Yuye; Chen, Linyu; Shi, Jia; Ma, Kang; Tang, Longhuang; Xu, Degang; Yao, Jianquan; Feng, Hua; Chen, Tunan

2018-03-01

We demonstrated that different degrees of experimental traumatic brain injury (TBI) can be differentiated clearly in fresh slices of rat brain tissues using transmission-type terahertz (THz) imaging system. The high absorption region in THz images corresponded well with the injured area in visible images and magnetic resonance imaging results. The THz image and absorption characteristics of dehydrated paraffin-embedded brain slices and the hematoxylin and eosin (H&E)-stained microscopic images were investigated to account for the intrinsic differences in the THz images for the brain tissues suffered from different degrees of TBI and normal tissue aside from water. The THz absorption coefficients of rat brain tissues showed an increase in the aggravation of brain damage, particularly in the high-frequency range, whereas the cell density decreased as the order of mild, moderate, and severe TBI tissues compared with the normal tissue. Our results indicated that the different degrees of TBI were distinguishable owing to the different water contents and probable hematoma components distribution rather than intrinsic cell intensity. These promising results suggest that THz imaging has great potential as an alternative method for the fast diagnosis of TBI.

Post-treatment Vascular Leakage and Inflammatory Responses around Brain Cysts in Porcine Neurocysticercosis

PubMed Central

Mahanty, Siddhartha; Orrego, Miguel Angel; Mayta, Holger; Marzal, Miguel; Cangalaya, Carla; Paredes, Adriana; Gonzales-Gustavson, Eloy; Arroyo, Gianfranco; Gonzalez, Armando E.; Guerra-Giraldez, Cristina; García, Hector H.; Nash, Theodore E.

2015-01-01

Cysticidal treatment of neurocysticercosis, an infection of humans and pig brains with Taenia solium, results in an early inflammatory response directed to cysts causing seizures and focal neurological manifestations. Treatment-induced pericystic inflammation and its association with blood brain barrier (BBB) dysfunction, as determined by Evans blue (EB) extravasation, was studied in infected untreated and anthelmintic-treated pigs. We compared the magnitude and extent of the pericystic inflammation, presence of EB-stained capsules, the level of damage to the parasite, expression of genes for proinflammatory and regulatory cytokines, chemokines, and tissue remodeling by quantitative PCR assays between treated and untreated infected pigs and between EB-stained (blue) and non stained (clear) cysts. Inflammatory scores were higher in pericystic tissues from EB-stained cysts compared to clear cysts from untreated pigs and also from anthelmintic-treated pigs 48 hr and 120 hr after treatment. The degree of inflammation correlated with the severity of cyst wall damage and both increased significantly at 120 hours. Expression levels of the proinflammatory genes for IL-6, IFN-γ, TNF-α were higher in EB-stained cysts compared to clear cysts and unaffected brain tissues, and were generally highest at 120 hr. Additionally, expression of some markers of immunoregulatory activity (IL-10, IL-2Rα) were decreased in EB-stained capsules. An increase in other markers for regulatory T cells (CTLA4, FoxP3) was found, as well as significant increases in expression of two metalloproteases, MMP1 and MMP2 at 48 hr and 120 hr post-treatment. We conclude that the increase in severity of the inflammation caused by treatment is accompanied by both a proinflammatory and a complex regulatory response, largely limited to pericystic tissues with compromised vascular integrity. Because treatment induced inflammation occurs in porcine NCC similar to that in human cases, this model can be used to investigate mechanisms involved in host damaging inflammatory responses and agents or modalities that may control damaging post treatment inflammation. PMID:25774662

Multicolor Fluorescence Imaging of Traumatic Brain Injury in a Cryolesion Mouse Model

PubMed Central

2012-01-01

Traumatic brain injury is characterized by initial tissue damage, which then can lead to secondary processes such as cell death and blood-brain-barrier disruption. Clinical and preclinical studies of traumatic brain injury typically employ anatomical imaging techniques and there is a need for new molecular imaging methods that provide complementary biochemical information. Here, we assess the ability of a targeted, near-infrared fluorescent probe, named PSS-794, to detect cell death in a brain cryolesion mouse model that replicates certain features of traumatic brain injury. In short, the model involves brief contact of a cold rod to the head of a living, anesthetized mouse. Using noninvasive whole-body fluorescence imaging, PSS-794 permitted visualization of the cryolesion in the living animal. Ex vivo imaging and histological analysis confirmed PSS-794 localization to site of brain cell death. The nontargeted, deep-red Tracer-653 was validated as a tracer dye for monitoring blood-brain-barrier disruption, and a binary mixture of PSS-794 and Tracer-653 was employed for multicolor imaging of cell death and blood-brain-barrier permeability in a single animal. The imaging data indicates that at 3 days after brain cryoinjury the amount of cell death had decreased significantly, but the integrity of the blood-brain-barrier was still impaired; at 7 days, the blood-brain-barrier was still three times more permeable than before cryoinjury. PMID:22860222

Effects of high-pressure oxygen therapy on brain tissue water content and AQP4 expression in rabbits with cerebral hemorrhage.

PubMed

Wu, Jing; Chen, Jiong; Guo, Hua; Peng, Fang

2014-12-01

To investigate the effects of different atmosphere absolutes (ATA) of high-pressure oxygen (HPO) on brain tissue water content and Aquaporin-4 (AQP4) expression in rabbits with cerebral hemorrhage. 180 New Zealand white rabbits were selected and randomly divided into normal group (n = 30), control group (n = 30) and cerebral hemorrhage group (n = 120), and cerebral hemorrhage group was divided into group A, B, C and D with 30 rabbits in each group. The groups received 1.0, 1.8, 2.0 and 2.2 ATA of HPO treatments, respectively. Ten rabbits in each group were killed at first, third and fifth day to detect the brain tissue water content and change of AQP4 expression. In cerebral hemorrhage group, brain tissue water content and AQP4 expression after model establishment were first increased, then decreased and reached the maximum on third day (p < 0.05). Brain tissue water content and AQP4 expression in control group and cerebral hemorrhage group were significantly higher than normal group at different time points (p < 0.05). In contrast, brain tissue water content and AQP4 expression in group C were significantly lower than in group A, group B, group D and control group (p < 0.05). In control group, AQP4-positive cells significantly increased after model establishment, which reached maximum on third day, and positive cells in group C were significantly less than in group A, group B and group D. We also found that AQP4 expression were positively correlated with brain tissue water content (r = 0.719, p < 0.05) demonstrated by significantly increased AQP4 expression along with increased brain tissue water content. In conclusion, HPO can decrease AQP4 expression in brain tissue of rabbits with cerebral hemorrhage to suppress the progression of brain edema and promote repairing of injured tissue. 2.0 ATA HPO exerts best effects, which provides an experimental basis for ATA selection of HPO in treating cerebral hemorrhage.

Central nervous system regulation of intestinal lipid and lipoprotein metabolism.

PubMed

Farr, Sarah; Taher, Jennifer; Adeli, Khosrow

2016-02-01

In response to nutrient availability, the small intestine and brain closely communicate to modulate energy homeostasis and metabolism. The gut-brain axis involves complex nutrient sensing mechanisms and an integration of neuronal and hormonal signaling. This review summarizes recent evidence implicating the gut-brain axis in regulating lipoprotein metabolism, with potential implications for the dyslipidemia of insulin resistant states. The intestine and brain possess distinct mechanisms for sensing lipid availability, which triggers subsequent regulation of feeding, glucose homeostasis, and adipose tissue metabolism. More recently, central receptors, neuropeptides, and gut hormones that communicate with the brain have been shown to modulate hepatic and intestinal lipoprotein metabolism via parasympathetic and sympathetic signaling. Gut-derived glucagon-like peptides appear to be particularly important in modulating the intestinal secretion of chylomicron particles via a novel brain-gut axis. Dysregulation of these pathways may contribute to postprandial diabetic dyslipidemia. Emerging evidence implicates the central and enteric nervous systems in controlling many aspects of lipid and lipoprotein metabolism. Bidirectional communication between the gut and brain involving neuronal pathways and gut peptides is critical for regulating feeding and metabolism, and forms a neuroendocrine circuit to modulate dietary fat absorption and intestinal production of atherogenic chylomicron particles.

Double dissociation of structure-function relationships in memory and fluid intelligence observed with magnetic resonance elastography.

PubMed

Johnson, Curtis L; Schwarb, Hillary; Horecka, Kevin M; McGarry, Matthew D J; Hillman, Charles H; Kramer, Arthur F; Cohen, Neal J; Barbey, Aron K

2018-05-01

Brain tissue mechanical properties, measured in vivo with magnetic resonance elastography (MRE), have proven to be sensitive metrics of neural tissue integrity. Recently, our group has reported on the positive relationship between viscoelasticity of the hippocampus and performance on a relational memory task in healthy young adults, which highlighted the potential of sensitive MRE measures for studying brain health and its relation to cognitive function; however, structure-function relationships outside of the hippocampus have not yet been explored. In this study, we examined the relationships between viscoelasticity of both the hippocampus and the orbitofrontal cortex and performance on behavioral assessments of relational memory and fluid intelligence. In a sample of healthy, young adults (N = 53), there was a significant, positive relationship between orbitofrontal cortex viscoelasticity and fluid intelligence performance (r = 0.42; p = .002). This finding is consistent with the previously reported relationship between hippocampal viscoelasticity and relational memory performance (r = 0.41; p = .002). Further, a significant double dissociation between the orbitofrontal-fluid intelligence relationship and the hippocampal-relational memory relationship was observed. These data support the specificity of regional brain MRE measures in support of separable cognitive functions. This report of a structure-function relationship observed with MRE beyond the hippocampus suggests a future role for MRE as a sensitive neuroimaging technique for brain mapping. Copyright © 2018 Elsevier Inc. All rights reserved.

Automated tissue segmentation of MR brain images in the presence of white matter lesions.

PubMed

Valverde, Sergi; Oliver, Arnau; Roura, Eloy; González-Villà, Sandra; Pareto, Deborah; Vilanova, Joan C; Ramió-Torrentà, Lluís; Rovira, Àlex; Lladó, Xavier

2017-01-01

Over the last few years, the increasing interest in brain tissue volume measurements on clinical settings has led to the development of a wide number of automated tissue segmentation methods. However, white matter lesions are known to reduce the performance of automated tissue segmentation methods, which requires manual annotation of the lesions and refilling them before segmentation, which is tedious and time-consuming. Here, we propose a new, fully automated T1-w/FLAIR tissue segmentation approach designed to deal with images in the presence of WM lesions. This approach integrates a robust partial volume tissue segmentation with WM outlier rejection and filling, combining intensity and probabilistic and morphological prior maps. We evaluate the performance of this method on the MRBrainS13 tissue segmentation challenge database, which contains images with vascular WM lesions, and also on a set of Multiple Sclerosis (MS) patient images. On both databases, we validate the performance of our method with other state-of-the-art techniques. On the MRBrainS13 data, the presented approach was at the time of submission the best ranked unsupervised intensity model method of the challenge (7th position) and clearly outperformed the other unsupervised pipelines such as FAST and SPM12. On MS data, the differences in tissue segmentation between the images segmented with our method and the same images where manual expert annotations were used to refill lesions on T1-w images before segmentation were lower or similar to the best state-of-the-art pipeline incorporating automated lesion segmentation and filling. Our results show that the proposed pipeline achieved very competitive results on both vascular and MS lesions. A public version of this approach is available to download for the neuro-imaging community. Copyright © 2016 Elsevier B.V. All rights reserved.

Monitoring brain temperature by time-resolved near-infrared spectroscopy: pilot study

NASA Astrophysics Data System (ADS)

Bakhsheshi, Mohammad Fazel; Diop, Mamadou; St. Lawrence, Keith; Lee, Ting-Yim

2014-05-01

Mild hypothermia (HT) is an effective neuroprotective strategy for a variety of acute brain injuries. However, the wide clinical adaptation of HT has been hampered by the lack of a reliable noninvasive method for measuring brain temperature, since core measurements have been shown to not always reflect brain temperature. The goal of this work was to develop a noninvasive optical technique for measuring brain temperature that exploits both the temperature dependency of water absorption and the high concentration of water in brain (80%-90%). Specifically, we demonstrate the potential of time-resolved near-infrared spectroscopy (TR-NIRS) to measure temperature in tissue-mimicking phantoms (in vitro) and deep brain tissue (in vivo) during heating and cooling, respectively. For deep brain tissue temperature monitoring, experiments were conducted on newborn piglets wherein hypothermia was induced by gradual whole body cooling. Brain temperature was concomitantly measured by TR-NIRS and a thermocouple probe implanted in the brain. Our proposed TR-NIRS method was able to measure the temperature of tissue-mimicking phantoms and brain tissues with a correlation of 0.82 and 0.66 to temperature measured with a thermometer, respectively. The mean difference between the TR-NIRS and thermometer measurements was 0.15°C±1.1°C for the in vitro experiments and 0.5°C±1.6°C for the in vivo measurements.

Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain.

PubMed

Taoka, Toshiaki; Naganawa, Shinji

2018-04-10

After Kanda's first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the 'glymphatic system', which is a coined word that combines 'gl' for glia cell and 'lymphatic' system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue.

Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System: Possible Mechanisms for the Deposition of Gadolinium in the Brain

PubMed Central

Taoka, Toshiaki; Naganawa, Shinji

2018-01-01

After Kanda’s first report in 2014 on gadolinium (Gd) deposition in brain tissue, a considerable number of studies have investigated the explanation for the observation. Gd deposition in brain tissue after repeated administration of gadolinium-based contrast medium (GBCM) has been histologically proven, and chelate stability has been shown to affect the deposition. However, the mechanism for this deposition has not been fully elucidated. Recently, a hypothesis was introduced that involves the ‘glymphatic system’, which is a coined word that combines ‘gl’ for glia cell and ‘lymphatic’ system. According to this hypothesis, the perivascular space functions as a conduit for cerebrospinal fluid to flow into the brain parenchyma. The perivascular space around the arteries allows cerebrospinal fluid to enter the interstitial space of the brain tissue through water channels controlled by aquaporin 4. The cerebrospinal fluid entering the interstitial space clears waste proteins from the tissue. It then flows into the perivascular space around the vein and is discharged outside the brain. In addition to the hypothesis regarding the glymphatic system, some reports have described that after GBCM administration, some of the GBCM distributes through systemic blood circulation and remains in other compartments including the cerebrospinal fluid. It is thought that the GBCM distributed into the cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue for a longer duration compared to the GBCM in systemic circulation. Glymphatic system may of course act as a clearance system for GBCM from brain tissue. Based on these findings, the mechanism for Gd deposition in the brain will be discussed in this review. The authors speculate that the glymphatic system may be the major contributory factor to the deposition and clearance of gadolinium in brain tissue. PMID:29367513

TU-G-210-00: Treatment Planning Strategies, Modeling, Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such asmore » the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)« less

Mathematical modelling of blood-brain barrier failure and edema

NASA Astrophysics Data System (ADS)

Waters, Sarah; Lang, Georgina; Vella, Dominic; Goriely, Alain

2015-11-01

Injuries such as traumatic brain injury and stroke can result in increased blood-brain barrier permeability. This increase may lead to water accumulation in the brain tissue resulting in vasogenic edema. Although the initial injury may be localised, the resulting edema causes mechanical damage and compression of the vasculature beyond the original injury site. We employ a biphasic mixture model to investigate the consequences of blood-brain barrier permeability changes within a region of brain tissue and the onset of vasogenic edema. We find that such localised changes can indeed result in brain tissue swelling and that the type of damage that results (stress damage or strain damage) depends on the ability of the brain to clear edema fluid.

Responses of the Human Brain to Mild Dehydration and Rehydration Explored In Vivo by 1H-MR Imaging and Spectroscopy.

PubMed

Biller, A; Reuter, M; Patenaude, B; Homola, G A; Breuer, F; Bendszus, M; Bartsch, A J

2015-12-01

As yet, there are no in vivo data on tissue water changes and associated morphometric changes involved in the osmo-adaptation of normal brains. Our aim was to evaluate osmoadaptive responses of the healthy human brain to osmotic challenges of de- and rehydration by serial measurements of brain volume, tissue fluid, and metabolites. Serial T1-weighted and (1)H-MR spectroscopy data were acquired in 15 healthy individuals at normohydration, on 12 hours of dehydration, and during 1 hour of oral rehydration. Osmotic challenges were monitored by serum measures, including osmolality and hematocrit. MR imaging data were analyzed by using FreeSurfer and LCModel. On dehydration, serum osmolality increased by 0.67% and brain tissue fluid decreased by 1.63%, on average. MR imaging morphometry demonstrated corresponding decreases of cortical thickness and volumes of the whole brain, cortex, white matter, and hypothalamus/thalamus. These changes reversed during rehydration. Continuous fluid ingestion of 1 L of water for 1 hour within the scanner lowered serum osmolality by 0.96% and increased brain tissue fluid by 0.43%, on average. Concomitantly, cortical thickness and volumes of the whole brain, cortex, white matter, and hypothalamus/thalamus increased. Changes in brain tissue fluid were related to volume changes of the whole brain, the white matter, and hypothalamus/thalamus. Only volume changes of the hypothalamus/thalamus significantly correlated with serum osmolality. This is the first study simultaneously evaluating changes in brain tissue fluid, metabolites, volume, and cortical thickness. Our results reflect cellular volume regulatory mechanisms at a macroscopic level and emphasize that it is essential to control for hydration levels in studies on brain morphometry and metabolism in order to avoid confounding the findings. © 2015 by American Journal of Neuroradiology.

White matter hyperintensities and normal-appearing white matter integrity in the aging brain.

PubMed

Maniega, Susana Muñoz; Valdés Hernández, Maria C; Clayden, Jonathan D; Royle, Natalie A; Murray, Catherine; Morris, Zoe; Aribisala, Benjamin S; Gow, Alan J; Starr, John M; Bastin, Mark E; Deary, Ian J; Wardlaw, Joanna M

2015-02-01

White matter hyperintensities (WMH) of presumed vascular origin are a common finding in brain magnetic resonance imaging of older individuals and contribute to cognitive and functional decline. It is unknown how WMH form, although white matter degeneration is characterized pathologically by demyelination, axonal loss, and rarefaction, often attributed to ischemia. Changes within normal-appearing white matter (NAWM) in subjects with WMH have also been reported but have not yet been fully characterized. Here, we describe the in vivo imaging signatures of both NAWM and WMH in a large group of community-dwelling older people of similar age using biomarkers derived from magnetic resonance imaging that collectively reflect white matter integrity, myelination, and brain water content. Fractional anisotropy (FA) and magnetization transfer ratio (MTR) were significantly lower, whereas mean diffusivity (MD) and longitudinal relaxation time (T1) were significantly higher, in WMH than NAWM (p < 0.0001), with MD providing the largest difference between NAWM and WMH. Receiver operating characteristic analysis on each biomarker showed that MD differentiated best between NAWM and WMH, identifying 94.6% of the lesions using a threshold of 0.747 × 10(-9) m(2)s(-1) (area under curve, 0.982; 95% CI, 0.975-0.989). Furthermore, the level of deterioration of NAWM was strongly associated with the severity of WMH, with MD and T1 increasing and FA and MTR decreasing in NAWM with increasing WMH score, a relationship that was sustained regardless of distance from the WMH. These multimodal imaging data indicate that WMH have reduced structural integrity compared with surrounding NAWM, and MD provides the best discriminator between the 2 tissue classes even within the mild range of WMH severity, whereas FA, MTR, and T1 only start reflecting significant changes in tissue microstructure as WMH become more severe. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Neuroprotective effect of interleukin-6 in a rat model of cerebral ischemia

PubMed Central

FENG, QILIN; WANG, YI; YANG, YINGDA

2015-01-01

Interleukin (IL)-6 is known to be a key cytokine in immune regulation in addition to serving crucial functions in various autoimmune diseases; however, the neuroprotective potential of IL-6 has not been fully investigated. The aim of the present study was to investigate the neuroprotective effects of the inflammatory cytokine IL-6 in a rat model of cerebral ischemia. Rat cerebral ischemia was induced by intraluminal middle cerebral artery occlusion. Following treatment with 500 or 50 ng IL-6, the infarct volumes and symptoms of neurological deficit were ameliorated. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining suggested that the IL-6 treatment reduced neuronal apoptosis in vivo, which was consistent with a lower percentage of annexin V- and caspase-3-positive cortical neurons. In addition, IL-6 in vitro induced the phosphorylation of signal transducer and activator of transcription (STAT) 3 and the expression of induced myeloid leukemia cell differentiation protein Mcl-1, but not the expression of B-cell lymphoma 2, suggesting the activation of the Janus kinase/STAT pathway by IL-6. IL-6 also appeared to be involved in the regulation of cytokine secretion and blood-brain barrier (BBB) integrity in cerebral ischemia. IL-6 downregulated a number of inflammatory cytokines, including tumor necrosis factor-α and IL-1β, as well as myeloperoxidase activity, indicating the accumulation of granulocytes in the ischemic brain tissue. IL-6 was also observed to support the integrity of the BBB by reducing Evans blue leakage in vivo and suppressing the expression of matrix metalloproteinase-9 in ischemic brain tissue. In conclusion, the results of the present study indicate that the neuroprotective effects of IL-6 in cerebral ischemia are the result of a range of processes, including the modulation of cell apoptosis, cytokine secretion and the integrity of the BBB. IL-6 could therefore be used as a therapeutic agent in clinical practice. PMID:26136879

Involvement of the endocannabinoid system in the physiological response to transient common carotid artery occlusion and reperfusion.

PubMed

Quartu, Marina; Poddighe, Laura; Melis, Tiziana; Serra, Maria Pina; Boi, Marianna; Lisai, Sara; Carta, Gianfranca; Murru, Elisabetta; Muredda, Laura; Collu, Maria; Banni, Sebastiano

2017-01-19

The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) may trigger a physiological response in an attempt to preserve tissue and function integrity. There are several candidate molecules among which the endocannabinoid system (ECS) and/or peroxisome-proliferator activated receptor-alpha (PPAR-alpha) may play a role in modulating oxidative stress and inflammation. The aims of the present study are to evaluate whether the ECS, the enzyme cyclooxygenase-2 (COX-2) and PPAR-alpha are involved during BCCAO/R in rat brain, and to identify possible markers of the ongoing BCCAO/R-induced challenge in plasma. Adult Wistar rats underwent BCCAO/R with 30 min hypoperfusion followed by 60 min reperfusion. The frontal and temporal-occipital cortices and plasma were analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS) to determine concentrations of endocannabinoids (eCBs) and related molecules behaving as ligands of PPAR-alpha, and of oxidative-stress markers such as lipoperoxides, while Western Blot and immunohistochemistry were used to study protein expression of cannabinoid receptors, COX-2 and PPAR-alpha. Unpaired Student's t-test was used to evaluate statistical differences between groups. The acute BCCAO/R procedure is followed by increased brain tissue levels of the eCBs 2-arachidonoylglycerol and anandamide, palmitoylethanolamide, an avid ligand of PPAR-alpha, lipoperoxides, type 1 (CB1) and type 2 (CB2) cannabinoid receptors, and COX-2, and decreased brain tissue concentrations of docosahexaenoic acid (DHA), one of the major targets of lipid peroxidation. In plasma, increased levels of anandamide and lipoperoxides were observed. The BCCAO/R stimulated early molecular changes that can be easily traced in brain tissue and plasma, and that are indicative of the tissue physiological response to the reperfusion-induced oxidative stress and inflammation. The observed variations suggest that the positive modulation of the ECS and the increase of proinflammatory substances are directly correlated events. Increase of plasmatic levels of anandamide and lipoperoxides further suggests that dysregulation of these molecules may be taken as an indicator of an ongoing hypoperfusion/reperfusion challenge.

Differential metabolism of 4-hydroxynonenal in liver, lung and brain of mice and rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Ruijin; Dragomir, Ana-Cristina; Mishin, Vladimir

2014-08-15

The lipid peroxidation end-product 4-hydroxynonenal (4-HNE) is generated in tissues during oxidative stress. As a reactive aldehyde, it forms Michael adducts with nucleophiles, a process that disrupts cellular functioning. Liver, lung and brain are highly sensitive to xenobiotic-induced oxidative stress and readily generate 4-HNE. In the present studies, we compared 4-HNE metabolism in these tissues, a process that protects against tissue injury. 4-HNE was degraded slowly in total homogenates and S9 fractions of mouse liver, lung and brain. In liver, but not lung or brain, NAD(P)+ and NAD(P)H markedly stimulated 4-HNE metabolism. Similar results were observed in rat S9 fractionsmore » from these tissues. In liver, lung and brain S9 fractions, 4-HNE formed protein adducts. When NADH was used to stimulate 4-HNE metabolism, the formation of protein adducts was suppressed in liver, but not lung or brain. In both mouse and rat tissues, 4-HNE was also metabolized by glutathione S-transferases. The greatest activity was noted in livers of mice and in lungs of rats; relatively low glutathione S-transferase activity was detected in brain. In mouse hepatocytes, 4-HNE was rapidly taken up and metabolized. Simultaneously, 4-HNE-protein adducts were formed, suggesting that 4-HNE metabolism in intact cells does not prevent protein modifications. These data demonstrate that, in contrast to liver, lung and brain have a limited capacity to metabolize 4-HNE. The persistence of 4-HNE in these tissues may increase the likelihood of tissue injury during oxidative stress. - Highlights: • Lipid peroxidation generates 4-hydroxynonenal, a highly reactive aldehyde. • Rodent liver, but not lung or brain, is efficient in degrading 4-hydroxynonenal. • 4-hydroxynonenal persists in tissues with low metabolism, causing tissue damage.« less

Dynamic monitoring of blood-brain barrier integrity using water exchange index (WEI) during mannitol and CO2 challenges in mouse brain.

PubMed

Huang, Shuning; Farrar, Christian T; Dai, Guangping; Kwon, Seon Joo; Bogdanov, Alexei A; Rosen, Bruce R; Kim, Young R

2013-04-01

The integrity of the blood-brain barrier (BBB) is critical to normal brain function. Traditional techniques for the assessment of BBB disruption rely heavily on the spatiotemporal analysis of extravasating contrast agents. However, such methods based on the leakage of relatively large molecules are not suitable for the detection of subtle BBB impairment or for the performance of repeated measurements in a short time frame. Quantification of the water exchange rate constant (WER) across the BBB using strictly intravascular contrast agents could provide a much more sensitive method for the quantification of the BBB integrity. To estimate WER, we have recently devised a powerful new method using a water exchange index (WEI) biomarker and demonstrated BBB disruption in an acute stroke model. Here, we confirm that WEI is sensitive to even very subtle changes in the integrity of the BBB caused by: (i) systemic hypercapnia and (ii) low doses of a hyperosmolar solution. In addition, we have examined the sensitivity and accuracy of WEI as a biomarker of WER using computer simulation. In particular, the dependence of the WEI-WER relation on changes in vascular blood volume, T1 relaxation of cellular magnetization and transcytolemmal water exchange was explored. Simulated WEI was found to vary linearly with WER for typically encountered exchange rate constants (1-4 Hz), regardless of the blood volume. However, for very high WER (>5 Hz), WEI became progressively more insensitive to increasing WER. The incorporation of transcytolemmal water exchange, using a three-compartment tissue model, helped to extend the linear WEI regime to slightly higher WER, but had no significant effect for most physiologically important WERs (WER < 4 Hz). Variation in cellular T1 had no effect on WEI. Using both theoretical and experimental approaches, our study validates the utility of the WEI biomarker for the monitoring of BBB integrity. Copyright © 2012 John Wiley & Sons, Ltd.

Dynamic Monitoring of Blood-Brain Barrier Integrity using Water Exchange Index (WEI) During Mannitol and CO2 Challenges in Mouse Brain

PubMed Central

Huang, Shuning; Farrar, Christian T.; Dai, Guangping; Kwon, Seon Joo; Bogdanov, Alexei A.; Rosen, Bruce R.; Kim, Young R.

2012-01-01

The integrity of the blood-brain barrier (BBB) is critical to normal brain function. Traditional techniques for assessing BBB disruption rely heavily on the spatiotemporal analysis of extravasating contrast agents. But such methods based on the leakage of relatively large molecules are not suitable to detect subtle BBB impairment or to perform repeated measurements in a short time frame. Quantification of the water exchange rate constant (WER) across the BBB using strictly intravascular contrast agents could provide a much more sensitive method for quantifying the BBB integrity. For estimating the WER, we have recently devised a powerful new method using a water exchange index (WEI) biomarker and demonstrated BBB disruption in an acute stroke model. Here we confirm that the WEI is sensitive to even very subtle changes in the integrity of the BBB caused by (1) systemic hypercapnia and (2) low doses of a hyperosmolar solution. In addition, we have examined the sensitivity and accuracy of the WEI as a biomarker of the WER using computer simulation. In particular, the dependence of the WEI-WER relation on changes in vascular blood volume, T1 relaxation of cellular magnetization, and transcytolemmal water exchange was explored. The simulated WEI was found to vary linearly with the WER for typically encountered exchange rate constants (1–4 Hz) regardless of the blood volume. However, for very high WER (>5 Hz) the WEI became progressively more insensitive to increasing WER. The incorporation of transcytolemmal water exchange, using a three-compartment tissue model, helped to extend the linear WEI regime to slightly higher WER, but had no significant effect for most physiologically important water exchange rate constants (WER<4 Hz). Variation in the cellular T1 had no effect on the WEI. Using both theoretical and experimental approaches, our study validates the utility of the WEI biomarker for monitoring BBB integrity. PMID:23055278

Effects of the Variation in Brain Tissue Mechanical Properties on the Intracranial Response of a 6-Year-Old Child

PubMed Central

Cui, Shihai; Li, Haiyan; Li, Xiangnan; Ruan, Jesse

2015-01-01

Brain tissue mechanical properties are of importance to investigate child head injury using finite element (FE) method. However, these properties used in child head FE model normally vary in a large range in published literatures because of the insufficient child cadaver experiments. In this work, a head FE model with detailed anatomical structures is developed from the computed tomography (CT) data of a 6-year-old healthy child head. The effects of brain tissue mechanical properties on traumatic brain response are also analyzed by reconstruction of a head impact on engine hood according to Euro-NCAP testing regulation using FE method. The result showed that the variations of brain tissue mechanical parameters in linear viscoelastic constitutive model had different influences on the intracranial response. Furthermore, the opposite trend was obtained in the predicted shear stress and shear strain of brain tissues caused by the variations of mentioned parameters. PMID:26495031

Brain cancer probed by native fluorescence and stokes shift spectroscopy

NASA Astrophysics Data System (ADS)

Zhou, Yan; Liu, Cheng-hui; He, Yong; Pu, Yang; Li, Qingbo; Wang, Wei; Alfano, Robert R.

2012-12-01

Optical biopsy spectroscopy was applied to diagnosis human brain cancer in vitro. The spectra of native fluorescence, Stokes shift and excitation spectra were obtained from malignant meningioma, benign, normal meningeal tissues and acoustic neuroma benign tissues. The wide excitation wavelength ranges were used to establish the criterion for distinguishing brain diseases. The alteration of fluorescence spectra between normal and abnormal brain tissues were identified by the characteristic fluorophores under the excitation with UV to visible wavelength range. It was found that the ratios of the peak intensities and peak position in both spectra of fluorescence and Stokes shift may be used to diagnose human brain meninges diseases. The preliminary analysis of fluorescence spectral data from cancer and normal meningeal tissues by basic biochemical component analysis model (BBCA) and Bayes classification model based on statistical methods revealed the changes of components, and classified the difference between cancer and normal human brain meningeal tissues in a predictions accuracy rate is 0.93 in comparison with histopathology and immunohistochemistry reports (gold standard).

Flexible deep brain neural probes based on a parylene tube structure

NASA Astrophysics Data System (ADS)

Zhao, Zhiguo; Kim, Eric; Luo, Hao; Zhang, Jinsheng; Xu, Yong

2018-01-01

Most microfabricated neural probes have limited shank length, which prevents them from reaching many deep brain structures. This paper reports deep brain neural probes with ultra-long penetrating shanks based on a simple but novel parylene tube structure. The mechanical strength of the parylene tube shank is temporarily enhanced during implantation by inserting a metal wire. The metal wire can be removed after implantation, making the implanted probe very flexible and thus minimizing the stress caused by micromotions of brain tissues. Optogenetic stimulation and chemical delivery capabilities can be potentially integrated by taking advantage of the tube structure. Single-shank prototypes with a shank length of 18.2 mm have been developed. The microfabrication process comprises of deep reactive ion etching (DRIE) of silicon, parylene conformal coating/refilling, and XeF2 isotropic silicon etching. In addition to bench-top insertion characterization, the functionality of developed probes has been preliminarily demonstrated by implanting into the amygdala of a rat and recording neural signals.

Dual modal ultra-bright nanodots with aggregation-induced emission and gadolinium-chelation for vascular integrity and leakage detection.

PubMed

Feng, Guangxue; Li, Jackson Liang Yao; Claser, Carla; Balachander, Akhila; Tan, Yingrou; Goh, Chi Ching; Kwok, Immanuel Weng Han; Rénia, Laurent; Tang, Ben Zhong; Ng, Lai Guan; Liu, Bin

2018-01-01

The study of blood brain barrier (BBB) functions is important for neurological disorder research. However, the lack of suitable tools and methods has hampered the progress of this field. Herein, we present a hybrid nanodot strategy, termed AIE-Gd dots, comprising of a fluorogen with aggregation-induced emission (AIE) characteristics as the core to provide bright and stable fluorescence for optical imaging, and gadolinium (Gd) for accurate quantification of vascular leakage via inductively-coupled plasma mass spectrometry (ICP-MS). In this report, we demonstrate that AIE-Gd dots enable direct visualization of brain vascular networks under resting condition, and that they form localized punctate aggregates and accumulate in the brain tissue during experimental cerebral malaria, indicative of hemorrhage and BBB malfunction. With its superior detection sensitivity and multimodality, we hereby propose that AIE-Gd dots can serve as a better alternative to Evans blue for visualization and quantification of changes in brain barrier functions. Copyright © 2017. Published by Elsevier Ltd.

Peroxisomes in brain development and function☆

PubMed Central

Berger, Johannes; Dorninger, Fabian; Forss-Petter, Sonja; Kunze, Markus

2016-01-01

Peroxisomes contain numerous enzymatic activities that are important for mammalian physiology. Patients lacking either all peroxisomal functions or a single enzyme or transporter function typically develop severe neurological deficits, which originate from aberrant development of the brain, demyelination and loss of axonal integrity, neuroinflammation or other neurodegenerative processes. Whilst correlating peroxisomal properties with a compilation of pathologies observed in human patients and mouse models lacking all or individual peroxisomal functions, we discuss the importance of peroxisomal metabolites and tissue- and cell type-specific contributions to the observed brain pathologies. This enables us to deconstruct the local and systemic contribution of individual metabolic pathways to specific brain functions. We also review the recently discovered variability of pathological symptoms in cases with unexpectedly mild presentation of peroxisome biogenesis disorders. Finally, we explore the emerging evidence linking peroxisomes to more common neurological disorders such as Alzheimer’s disease, autism and amyotrophic lateral sclerosis. This article is part of a Special Issue entitled: Peroxisomes edited by Ralf Erdmann. PMID:26686055

A novel approach to segmentation and measurement of medical image using level set methods.

PubMed

Chen, Yao-Tien

2017-06-01

The study proposes a novel approach for segmentation and visualization plus value-added surface area and volume measurements for brain medical image analysis. The proposed method contains edge detection and Bayesian based level set segmentation, surface and volume rendering, and surface area and volume measurements for 3D objects of interest (i.e., brain tumor, brain tissue, or whole brain). Two extensions based on edge detection and Bayesian level set are first used to segment 3D objects. Ray casting and a modified marching cubes algorithm are then adopted to facilitate volume and surface visualization of medical-image dataset. To provide physicians with more useful information for diagnosis, the surface area and volume of an examined 3D object are calculated by the techniques of linear algebra and surface integration. Experiment results are finally reported in terms of 3D object extraction, surface and volume rendering, and surface area and volume measurements for medical image analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

Protective effects of angiopoietin-like 4 on the blood-brain barrier in acute ischemic stroke treated with thrombolysis in mice.

PubMed

Zhang, Bin; Xu, Xiaofeng; Chu, Xiuli; Yu, Xiaoyang; Zhao, Yuwu

2017-04-03

Given the risk of blood-brain barrier damage (BBB) caused by ischemic and tissue plasminogen activator thrombolysis, the preservation of vascular integrity is important. Angiopoietin-like 4 (ANGPTL4), a protein secreted in hypoxia, is involved in the regulation of vascular permeability. We hypothesized that Angptl4 might exert a protective effect in thrombolysis through stabilizing blood-brain barrier and inhibit hyper-permeability. We investigated the role of Angptl4 in stroke using a transient focal cerebral ischemia mouse model. The treated mice were administered Angptl4 1h after the ischemic event upon reperfusion. Our results showed that Angptl4 combined with thrombolysis greatly reduced the infarct volume and consequent neurological deficit. Western blot analyses and gelatin zymography revealed that Angptl4 protected the integrity of the endothelium damaged by thrombolysis. Angptl4 inhibited the up-regulation of vascular endothelial growth factor (VEGF) in the vascular endothelium after stroke, which was suppressed by counteracting VEGFR signaling and diminishing downstream Src signaling, and led to the increased stability of junctions and improved endothelial cell barrier integrity. These findings demonstrated that Angptl4 protects the permeability of the BBB damaged by ischemic and thrombolysis. Suggested that Angptl4 might be a promising target molecule in therapies for vasoprotection after thrombolysis treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Fasting for 21days leads to changes in adipose tissue and liver physiology in juvenile checkered garter snakes (Thamnophis marcianus).

PubMed

Davis, Mary; Jessee, Renee; Close, Matthew; Fu, Xiangping; Settlage, Robert; Wang, Guoqing; Cline, Mark A; Gilbert, Elizabeth R

2015-12-01

Snakes often undergo periods of prolonged fasting and, under certain conditions, can survive years without food. Despite this unique phenomenon, there are relatively few reports of the physiological adaptations to fasting in snakes. At post-prandial day 1 (fed) or 21 (fasting), brain, liver, and adipose tissues were collected from juvenile checkered garter snakes (Thamnophis marcianus). There was greater glycerol-3-phosphate dehydrogenase (G3PDH)-specific activity in the liver of fasted than fed snakes (P=0.01). The mRNA abundance of various fat metabolism-associated factors was measured in brain, liver, and adipose tissue. Lipoprotein lipase (LPL) mRNA was greater in fasted than fed snakes in the brain (P=0.04). Adipose triglyceride lipase (ATGL; P=0.006) mRNA was greater in the liver of fasted than fed snakes. In adipose tissue, expression of peroxisome proliferator-activated receptor (PPAR)γ (P=0.01), and fatty acid binding protein 4 (P=0.03) was greater in fed than fasted snakes. Analysis of adipocyte morphology revealed that cross-sectional area (P=0.095) and diameter (P=0.27) were not significantly different between fed and fasted snakes. Results suggest that mean adipocyte area can be preserved during fasting by dampening lipid biosynthesis while not changing rates of lipid hydrolysis. In the liver, however, extensive lipid remodeling may provide energy and lipoproteins to maintain lipid structural integrity during energy restriction. Because the duration of fasting was not sufficient to change adipocyte size, results suggest that the liver is important as a short-term provider of energy in the snake. Copyright © 2015 Elsevier Inc. All rights reserved.

Backscatter and attenuation properties of mammalian brain tissues

NASA Astrophysics Data System (ADS)

Wijekularatne, Pushpani Vihara

Traumatic Brain Injury (TBI) is a common category of brain injuries, which contributes to a substantial number of deaths and permanent disability all over the world. Ultrasound technology plays a major role in tissue characterization due to its low cost and portability that could be used to bridge a wide gap in the TBI diagnostic process. This research addresses the ultrasonic properties of mammalian brain tissues focusing on backscatter and attenuation. Orientation dependence and spatial averaging of data were analyzed using the same method resulting from insertion of tissue sample between a transducer and a reference reflector. Apparent backscatter transfer function (ABTF) at 1 to 10 MHz, attenuation coefficient and backscatter coefficient (BSC) at 1 to 5 MHz frequency ranges were measured on ovine brain tissue samples. The resulting ABTF was a monotonically decreasing function of frequency and the attenuation coefficient and BSC generally were increasing functions of frequency, results consistent with other soft tissues such as liver, blood and heart.

Brain Death and Human Organismal Integration: A Symposium on the Definition of Death.

PubMed

Moschella, Melissa

2016-06-01

Does the ability of some brain dead bodies to maintain homeostasis with the help of artificial life support actually imply that those bodies are living human organisms? Or might it be possible that a brain dead body on life support is a mere collection of still-living cells, organs and tissues which can coordinate with one another, but which lack the genuine integration that is the hallmark of a unified human organism as a whole? To foster further study of these difficult and timely questions, a Symposium on the Definition of Death was held at The Catholic University of America in June 2014. The Symposium brought together scholars from a variety of disciplines-law, medicine, biology, philosophy and theology-who all share a commitment to the dead donor rule and to a biological definition of death, but who have differing opinions regarding the validity of neurological criteria for human death. The papers found in this special issue are among the fruits of this Symposium. © The Author 2016. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A Dense Poly(ethylene glycol) Coating Improves Penetration of Large Polymeric Nanoparticles within Brain Tissue

PubMed Central

Nance, Elizabeth A.; Woodworth, Graeme F.; Sailor, Kurt A.; Shih, Ting-Yu; Xu, Qingguo; Swaminathan, Ganesh; Xiang, Dennis; Eberhart, Charles; Hanes, Justin

2013-01-01

Prevailing opinion suggests that only substances up to 64 nm in diameter can move at appreciable rates through the brain extracellular space (ECS). This size range is large enough to allow diffusion of signaling molecules, nutrients, and metabolic waste products, but too small to allow efficient penetration of most particulate drug delivery systems and viruses carrying therapeutic genes, thereby limiting effectiveness of many potential therapies. We analyzed the movements of nanoparticles of various diameters and surface coatings within fresh human and rat brain tissue ex vivo and mouse brain in vivo. Nanoparticles as large as 114-nm in diameter diffused within the human and rat brain, but only if they were densely coated with poly(ethylene glycol) (PEG). Using these minimally adhesive PEG-coated particles, we estimated that human brain tissue ECS has some pores larger than 200 nm, and that more than one-quarter of all pores are ≥100 nm. These findings were confirmed in vivo in mice, where 40- and 100-nm, but not 200-nm, nanoparticles, spread rapidly within brain tissue, only if densely coated with PEG. Similar results were observed in rat brain tissue with paclitaxel-loaded biodegradable nanoparticles of similar size (85 nm) and surface properties. The ability to achieve brain penetration with larger nanoparticles is expected to allow more uniform, longer-lasting, and effective delivery of drugs within the brain, and may find use in the treatment of brain tumors, stroke, neuroinflammation, and other brain diseases where the blood-brain barrier is compromised or where local delivery strategies are feasible. PMID:22932224

Nitric Oxide Protects against Infection-Induced Neuroinflammation by Preserving the Stability of the Blood-Brain Barrier

PubMed Central

Olivera, Gabriela C.; Ren, Xiaoyuan; Vodnala, Suman K.; Lu, Jun; Coppo, Lucia; Leepiyasakulchai, Chaniya; Holmgren, Arne; Kristensson, Krister; Rottenberg, Martin E.

2016-01-01

Nitric oxide (NO) generated by inducible NO synthase (iNOS) is critical for defense against intracellular pathogens but may mediate inflammatory tissue damage. To elucidate the role of iNOS in neuroinflammation, infections with encephalitogenic Trypanosoma brucei parasites were compared in inos -/- and wild-type mice. Inos -/- mice showed enhanced brain invasion by parasites and T cells, and elevated protein permeability of cerebral vessels, but similar parasitemia levels. Trypanosome infection stimulated T cell- and TNF-mediated iNOS expression in perivascular macrophages. NO nitrosylated and inactivated pro-inflammatory molecules such as NF-κΒp65, and reduced TNF expression and signalling. iNOS-derived NO hampered both TNF- and T cell-mediated parasite brain invasion. In inos -/- mice, TNF stimulated MMP, including MMP9 activity that increased cerebral vessel permeability. Thus, iNOS-generated NO by perivascular macrophages, strategically located at sites of leukocyte brain penetration, can serve as a negative feed-back regulator that prevents unlimited influx of inflammatory cells by restoring the integrity of the blood-brain barrier. PMID:26915097

Antigen recovery and preservation using the microwave irradiation of biological samples for transmission electron microscopy analysis.

PubMed

Aïoun, Josiane; Chat, Sophie; Bordat, Christian; Péchoux, Christine

2013-01-01

Most studies using microwave irradiation (MWI) for the preparation of tissue samples have reported an improvement in structural integrity. However, there have been few studies on the effect of microwave (MW) on antigen preservation during sample preparation prior to immunolocalization. This report documents our experience of specimen preparation using an automatic microwave apparatus to obtain antigen preservation and retrieval. We tested the effects of MW processing vs. conventional procedures on the morphology and antigenicity of two different tissues: the brain and mammary gland, whose chemical composition and anatomical organization are quite different. We chose to locate the transcription factor PPARβ/δ using immunocytochemistry on brain tissue sections from hamsters. Antigen retrieval protocols involving MWI were used to restore immunoreactivity. We also studied the efficiency of the ultrastructural immunolocalization of both PPARγ and caveolin-1 following MWI vs. conventional treatment, on mammary gland tissue from mice at 10 days of lactation. Our findings showed that the treatment of tissue samples with MWI, in the context of a process lasting just a few hours from fixation to immunolocalization, enabled similar, or even better, results than conventional protocols. The quantification of immunolabeling for cav-1 indicated an increase in density of up to three-fold in tissues processed in the microwave oven. Furthermore, MW treatment permitted the localization of PPARβ/δ in glutaraldehyde-fixed specimens, which was impossible in the absence of MWI. This study thus showed that techniques involving the use of microwaves could largely improve both ultrastructure and immunodetection. Copyright © 2013 Elsevier Ltd. All rights reserved.

An intraoperative spectroscopic imaging system for quantification of Protoporphyrin IX during glioma surgery (Conference Presentation)

NASA Astrophysics Data System (ADS)

Angulo-Rodríguez, Leticia M.; Laurence, Audrey; Jermyn, Michael; Sheehy, Guillaume; Sibai, Mira; Petrecca, Kevin; Roberts, David W.; Paulsen, Keith D.; Wilson, Brian C.; Leblond, Frédéric

2016-03-01

Cancer tissue often remains after brain tumor resection due to the inability to detect the full extent of cancer during surgery, particularly near tumor boundaries. Commercial systems are available for intra-operative real-time aminolevulenic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence imaging. These are standard white-light neurosurgical microscopes adapted with optical components for fluorescence excitation and detection. However, these instruments lack sensitivity and specificity, which limits the ability to detect low levels of PpIX and distinguish it from tissue auto-fluorescence. Current systems also cannot provide repeatable and un-biased quantitative fluorophore concentration values because of the unknown and highly variable light attenuation by tissue. We present a highly sensitive spectroscopic fluorescence imaging system that is seamlessly integrated onto a neurosurgical microscope. Hardware and software were developed to achieve through-microscope spatially-modulated illumination for 3D profilometry and to use this information to extract tissue optical properties to correct for the effects of tissue light attenuation. This gives pixel-by-pixel quantified fluorescence values and improves detection of low PpIX concentrations. This is achieved using a high-sensitivity Electron Multiplying Charge Coupled Device (EMCCD) with a Liquid Crystal Tunable Filter (LCTF) whereby spectral bands are acquired sequentially; and a snapshot camera system with simultaneous acquisition of all bands is used for profilometry and optical property recovery. Sensitivity and specificity to PpIX is demonstrated using brain tissue phantoms and intraoperative human data acquired in an on-going clinical study using PpIX fluorescence to guide glioma resection.

Fiber optic based multiparametric spectroscopy in vivo: Toward a new quantitative tissue vitality index

NASA Astrophysics Data System (ADS)

Kutai-Asis, Hofit; Barbiro-Michaely, Efrat; Deutsch, Assaf; Mayevsky, Avraham

2006-02-01

In our previous publication (Mayevsky et al SPIE 5326: 98-105, 2004) we described a multiparametric fiber optic system enabling the evaluation of 4 physiological parameters as indicators of tissue vitality. Since the correlation between the various parameters may differ in various pathophysiological conditions there is a need for an objective quantitative index that will integrate the relative changes measured in real time by the multiparametric monitoring system into a single number-vitality index. Such an approach to calculate tissue vitality index is critical for the possibility to use such an instrument in clinical environments. In the current presentation we are reporting our preliminary results indicating that calculation of an objective tissue vitality index is feasible. We used an intuitive empirical approach based on the comparison between the calculated index by the computer and the subjective evaluation made by an expert in the field of physiological monitoring. We used the in vivo brain of rats as an animal model in our current studies. The rats were exposed to anoxia, ischemia and cortical spreading depression and the responses were recorded in real time. At the end of the monitoring session the results were analyzed and the tissue vitality index was calculated offline. Mitochondrial NADH, tissue blood flow and oxy-hemoglobin were used to calculate the vitality index of the brain in vivo, where each parameter received a different weight, in each experiment type based on their significance. It was found that the mitochondrial NADH response was the main factor affected the calculated vitality index.

Determination of friction coefficient in unconfined compression of brain tissue.

PubMed

Rashid, Badar; Destrade, Michel; Gilchrist, Michael D

2012-10-01

Unconfined compression tests are more convenient to perform on cylindrical samples of brain tissue than tensile tests in order to estimate mechanical properties of the brain tissue because they allow homogeneous deformations. The reliability of these tests depends significantly on the amount of friction generated at the specimen/platen interface. Thus, there is a crucial need to find an approximate value of the friction coefficient in order to predict a possible overestimation of stresses during unconfined compression tests. In this study, a combined experimental-computational approach was adopted to estimate the dynamic friction coefficient μ of porcine brain matter against metal platens in compressive tests. Cylindrical samples of porcine brain tissue were tested up to 30% strain at variable strain rates, both under bonded and lubricated conditions in the same controlled environment. It was established that μ was equal to 0.09±0.03, 0.18±0.04, 0.18±0.04 and 0.20±0.02 at strain rates of 1, 30, 60 and 90/s, respectively. Additional tests were also performed to analyze brain tissue under lubricated and bonded conditions, with and without initial contact of the top platen with the brain tissue, with different specimen aspect ratios and with different lubricants (Phosphate Buffer Saline (PBS), Polytetrafluoroethylene (PTFE) and Silicone). The test conditions (lubricant used, biological tissue, loading velocity) adopted in this study were similar to the studies conducted by other research groups. This study will help to understand the amount of friction generated during unconfined compression of brain tissue for strain rates of up to 90/s. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dielectric properties of dog brain tissue measured in vitro across the 0.3-3 GHz band.

PubMed

Mohammed, Beadaa; Bialkowski, Konstanty; Abbosh, Amin; Mills, Paul C; Bradley, Andrew P

2016-09-22

Dielectric properties of dead Greyhound female dogs' brain tissues at different ages were measured at room temperature across the frequency range of 0.3-3 GHz. Measurements were made on excised tissues, in vitro in the laboratory, to carry out dielectric tests on sample tissues. Each dataset for a brain tissue was parametrized using the Cole-Cole expression, and the relevant Cole-Cole parameters for four tissue types are provided. A comparison was made with the database available in literature for other animals and human brain tissue. Results of two types of tissues (white matter and skull) showed systematic variation in dielectric properties as a function of animal age, whereas no significant change related to age was noticed for other tissues. Results provide critical information regarding dielectric properties of animal tissues for a realistic animal head model that can be used to verify the validity and reliability of a microwave head scanner for animals prior to testing on live animals. Bioelectromagnetics. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Brain tissue segmentation based on DTI data

PubMed Central

Liu, Tianming; Li, Hai; Wong, Kelvin; Tarokh, Ashley; Guo, Lei; Wong, Stephen T.C.

2008-01-01

We present a method for automated brain tissue segmentation based on the multi-channel fusion of diffusion tensor imaging (DTI) data. The method is motivated by the evidence that independent tissue segmentation based on DTI parametric images provides complementary information of tissue contrast to the tissue segmentation based on structural MRI data. This has important applications in defining accurate tissue maps when fusing structural data with diffusion data. In the absence of structural data, tissue segmentation based on DTI data provides an alternative means to obtain brain tissue segmentation. Our approach to the tissue segmentation based on DTI data is to classify the brain into two compartments by utilizing the tissue contrast existing in a single channel. Specifically, because the apparent diffusion coefficient (ADC) values in the cerebrospinal fluid (CSF) are more than twice that of gray matter (GM) and white matter (WM), we use ADC images to distinguish CSF and non-CSF tissues. Additionally, fractional anisotropy (FA) images are used to separate WM from non-WM tissues, as highly directional white matter structures have much larger fractional anisotropy values. Moreover, other channels to separate tissue are explored, such as eigenvalues of the tensor, relative anisotropy (RA), and volume ratio (VR). We developed an approach based on the Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm that combines these two-class maps to obtain a complete tissue segmentation map of CSF, GM, and WM. Evaluations are provided to demonstrate the performance of our approach. Experimental results of applying this approach to brain tissue segmentation and deformable registration of DTI data and spoiled gradient-echo (SPGR) data are also provided. PMID:17804258

Accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue.

PubMed

Zhang, Jing; Fan, Yimeng; He, Min; Ma, Xuelei; Song, Yanlin; Liu, Ming; Xu, Jianguo

2017-05-30

Raman spectroscopy could be applied to distinguish tumor from normal tissues. This meta-analysis was conducted to assess the accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue. PubMed and Embase were searched to identify suitable studies prior to Jan 1st, 2016. We estimated the pooled sensitivity, specificity, positive and negative likelihood ratios (LR), diagnostic odds ratio (DOR), and constructed summary receiver operating characteristics (SROC) curves to identity the accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue. A total of six studies with 1951 spectra were included. For glioma, the pooled sensitivity and specificity of Raman spectroscopy were 0.96 (95% CI 0.94-0.97) and 0.99 (95% CI 0.98-0.99), respectively. The area under the curve (AUC) was 0.9831. For meningioma, the pooled sensitivity and specificity were 0.98 (95% CI 0.94-1.00) and 1.00 (95% CI 0.98-1.00), respectively. The AUC was 0.9955. This meta-analysis suggested that Raman spectroscopy could be an effective and accurate tool for differentiating glioma and meningioma from normal brain tissue, which would help us both avoid removal of normal tissue and minimize the volume of residual tumor.

Typical and atypical brain development: a review of neuroimaging studies

PubMed Central

Dennis, Emily L.; Thompson, Paul M.

2013-01-01

In the course of development, the brain undergoes a remarkable process of restructuring as it adapts to the environment and becomes more efficient in processing information. A variety of brain imaging methods can be used to probe how anatomy, connectivity, and function change in the developing brain. Here we review recent discoveries regarding these brain changes in both typically developing individuals and individuals with neurodevelopmental disorders. We begin with typical development, summarizing research on changes in regional brain volume and tissue density, cortical thickness, white matter integrity, and functional connectivity. Space limits preclude the coverage of all neurodevelopmental disorders; instead, we cover a representative selection of studies examining neural correlates of autism, attention deficit/hyperactivity disorder, Fragile X, 22q11.2 deletion syndrome, Williams syndrome, Down syndrome, and Turner syndrome. Where possible, we focus on studies that identify an age by diagnosis interaction, suggesting an altered developmental trajectory. The studies we review generally cover the developmental period from infancy to early adulthood. Great progress has been made over the last 20 years in mapping how the brain matures with MR technology. With ever-improving technology, we expect this progress to accelerate, offering a deeper understanding of brain development, and more effective interventions for neurodevelopmental disorders. PMID:24174907

Typical and atypical brain development: a review of neuroimaging studies.

PubMed

Dennis, Emily L; Thompson, Paul M

2013-09-01

In the course of development, the brain undergoes a remarkable process of restructuring as it adapts to the environment and becomes more efficient in processing information. A variety of brain imaging methods can be used to probe how anatomy, connectivity, and function change in the developing brain. Here we review recent discoveries regarding these brain changes in both typically developing individuals and individuals with neurodevelopmental disorders. We begin with typical development, summarizing research on changes in regional brain volume and tissue density, cortical thickness, white matter integrity, and functional connectivity. Space limits preclude the coverage of all neurodevelopmental disorders; instead, we cover a representative selection of studies examining neural correlates of autism, attention deficit/hyperactivity disorder, Fragile X, 22q11.2 deletion syndrome, Williams syndrome, Down syndrome, and Turner syndrome. Where possible, we focus on studies that identify an age by diagnosis interaction, suggesting an altered developmental trajectory. The studies we review generally cover the developmental period from infancy to early adulthood. Great progress has been made over the last 20 years in mapping how the brain matures with MR technology. With ever-improving technology, we expect this progress to accelerate, offering a deeper understanding of brain development, and more effective interventions for neurodevelopmental disorders.

The Identification of Aluminum in Human Brain Tissue Using Lumogallion and Fluorescence Microscopy

PubMed Central

Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

2016-01-01

Aluminum in human brain tissue is implicated in the etiologies of neurodegenerative diseases including Alzheimer’s disease. While methods for the accurate and precise measurement of aluminum in human brain tissue are widely acknowledged, the same cannot be said for the visualization of aluminum. Herein we have used transversely-heated graphite furnace atomic absorption spectrometry to measure aluminum in the brain of a donor with Alzheimer’s disease, and we have developed and validated fluorescence microscopy and the fluor lumogallion to show the presence of aluminum in the same tissue. Aluminum is observed as characteristic orange fluorescence that is neither reproduced by other metals nor explained by autofluorescence. This new and relatively simple method to visualize aluminum in human brain tissue should enable more rigorous testing of the aluminum hypothesis of Alzheimer’s disease (and other neurological conditions) in the future. PMID:27472886

Deep two-photon microscopic imaging through brain tissue using the second singlet state from fluorescent agent chlorophyll α in spinach leaf

NASA Astrophysics Data System (ADS)

Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; An Nguyen, Thien; Alfano, Robert R.

2014-06-01

Two-photon (2P) excitation of the second singlet (S) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S2 state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.

Deep two-photon microscopic imaging through brain tissue using the second singlet state from fluorescent agent chlorophyll α in spinach leaf.

PubMed

Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; Nguyen, Thien An; Alfano, Robert R

2014-06-01

Two-photon (2P) excitation of the second singlet (S₂) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S₂ state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S₂ state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.

Functional characterization of enzymes catalyzing ceramide phosphoethanolamine biosynthesis in mice.

PubMed

Bickert, Andreas; Ginkel, Christina; Kol, Matthijs; vom Dorp, Katharina; Jastrow, Holger; Degen, Joachim; Jacobs, René L; Vance, Dennis E; Winterhager, Elke; Jiang, Xian-Cheng; Dörmann, Peter; Somerharju, Pentti; Holthuis, Joost C M; Willecke, Klaus

2015-04-01

Besides bulk amounts of SM, mammalian cells produce small quantities of the SM analog ceramide phosphoethanolamine (CPE). Little is known about the biological role of CPE or enzymes responsible for CPE production. Heterologous expression studies revealed that SM synthase (SMS)2 is a bifunctional enzyme producing both SM and CPE, whereas SMS-related protein (SMSr) serves as monofunctional CPE synthase. Acute disruption of SMSr catalytic activity in cultured cells causes a rise in endoplasmic reticulum (ER) ceramides, fragmentation of ER exit sites, and induction of mitochondrial apoptosis. To address the relevance of CPE biosynthesis in vivo, we analyzed the tissue-specific distribution of CPE in mice and generated mouse lines lacking SMSr and SMS2 catalytic activity. We found that CPE levels were >300-fold lower than SM in all tissues examined. Unexpectedly, combined inactivation of SMSr and SMS2 significantly reduced, but did not eliminate, tissue-specific CPE pools and had no obvious impact on mouse development or fertility. While SMSr is widely expressed and serves as the principal CPE synthase in the brain, blocking its catalytic activity did not affect ceramide levels or secretory pathway integrity in the brain or any other tissue. Our data provide a first inventory of CPE species and CPE-biosynthetic enzymes in mammals. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Conformable actively multiplexed high-density surface electrode array for brain interfacing

DOEpatents

Rogers, John; Kim, Dae-Hyeong; Litt, Brian; Viventi, Jonathan

2015-01-13

Provided are methods and devices for interfacing with brain tissue, specifically for monitoring and/or actuation of spatio-temporal electrical waveforms. The device is conformable having a high electrode density and high spatial and temporal resolution. A conformable substrate supports a conformable electronic circuit and a barrier layer. Electrodes are positioned to provide electrical contact with a brain tissue. A controller monitors or actuates the electrodes, thereby interfacing with the brain tissue. In an aspect, methods are provided to monitor or actuate spatio-temporal electrical waveform over large brain surface areas by any of the devices disclosed herein.

Unifying framework for multimodal brain MRI segmentation based on Hidden Markov Chains.

PubMed

Bricq, S; Collet, Ch; Armspach, J P

2008-12-01

In the frame of 3D medical imaging, accurate segmentation of multimodal brain MR images is of interest for many brain disorders. However, due to several factors such as noise, imaging artifacts, intrinsic tissue variation and partial volume effects, tissue classification remains a challenging task. In this paper, we present a unifying framework for unsupervised segmentation of multimodal brain MR images including partial volume effect, bias field correction, and information given by a probabilistic atlas. Here-proposed method takes into account neighborhood information using a Hidden Markov Chain (HMC) model. Due to the limited resolution of imaging devices, voxels may be composed of a mixture of different tissue types, this partial volume effect is included to achieve an accurate segmentation of brain tissues. Instead of assigning each voxel to a single tissue class (i.e., hard classification), we compute the relative amount of each pure tissue class in each voxel (mixture estimation). Further, a bias field estimation step is added to the proposed algorithm to correct intensity inhomogeneities. Furthermore, atlas priors were incorporated using probabilistic brain atlas containing prior expectations about the spatial localization of different tissue classes. This atlas is considered as a complementary sensor and the proposed method is extended to multimodal brain MRI without any user-tunable parameter (unsupervised algorithm). To validate this new unifying framework, we present experimental results on both synthetic and real brain images, for which the ground truth is available. Comparison with other often used techniques demonstrates the accuracy and the robustness of this new Markovian segmentation scheme.

Ethyl pyruvate protects against blood-brain barrier damage and improves long-term neurological outcomes in a rat model of traumatic brain injury.

PubMed

Shi, Hong; Wang, Hai-Lian; Pu, Hong-Jian; Shi, Ye-Jie; Zhang, Jia; Zhang, Wen-Ting; Wang, Guo-Hua; Hu, Xiao-Ming; Leak, Rehana K; Chen, Jun; Gao, Yan-Qin

2015-04-01

Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced long-term brain damage. Ethyl pyruvate (EP) has shown neuroprotection in several models of acute brain injury. The present study therefore investigated the potential beneficial effect of EP on long-term outcomes after TBI and the underlying mechanisms. Male adult rats were subjected to unilateral controlled cortical impact injury. EP was injected intraperitoneally 15 min after TBI and again at 12, 24, 36, 48, and 60 h after TBI. Neurological deficits, blood-brain barrier (BBB) integrity, and neuroinflammation were assessed. Ethyl pyruvate improved sensorimotor and cognitive functions and ameliorated brain tissue damage up to 28 day post-TBI. BBB breach and brain edema were attenuated by EP at 48 h after TBI. EP suppressed matrix metalloproteinase (MMP)-9 production from peripheral neutrophils and reduced the number of MMP-9-overproducing neutrophils in the spleen, and therefore mitigated MMP-9-mediated BBB breakdown. Moreover, EP exerted potent antiinflammatory effects in cultured microglia and inhibited the elevation of inflammatory mediators in the brain after TBI. Ethyl pyruvate confers long-term neuroprotection against TBI, possibly through breaking the vicious cycle among MMP-9-mediated BBB disruption, neuroinflammation, and long-lasting brain damage. © 2014 John Wiley & Sons Ltd.

Hypothalamic Integration of the Endocrine Signaling Related to Food Intake.

PubMed

Klockars, Anica; Levine, Allen S; Olszewski, Pawel K

2018-06-10

Hypothalamic integration of gastrointestinal and adipose tissue-derived hormones serves as a key element of neuroendocrine control of food intake. Leptin, adiponectin, oleoylethanolamide, cholecystokinin, and ghrelin, to name a few, are in a constant "cross talk" with the feeding-related brain circuits that encompass hypothalamic populations synthesizing anorexigens (melanocortins, CART, oxytocin) and orexigens (Agouti-related protein, neuropeptide Y, orexins). While this integrated neuroendocrine circuit successfully ensures that enough energy is acquired, it does not seem to be equally efficient in preventing excessive energy intake, especially in the obesogenic environment in which highly caloric and palatable food is constantly available. The current review presents an overview of intricate mechanisms underlying hypothalamic integration of energy balance-related peripheral endocrine input. We discuss vulnerabilities and maladaptive neuroregulatory processes, including changes in hypothalamic neuronal plasticity that propel overeating despite negative consequences.

Expression of neuronal and signaling proteins in penumbra around a photothrombotic infarction core in rat cerebral cortex.

PubMed

Demyanenko, S V; Panchenko, S N; Uzdensky, A B

2015-06-01

Photodynamic impact on animal cerebral cortex using water-soluble Bengal Rose as a photosensitizer, which does not cross the blood-brain barrier and remains in blood vessels, induces platelet aggregation, vessel occlusion, and brain tissue infarction. This reproduces ischemic stroke. Irreversible cell damage within the infarction core propagates to adjacent tissue and forms a transition zone - the penumbra. Tissue necrosis in the infarction core is too fast (minutes) to be prevented, but much slower penumbral injury (hours) can be limited. We studied the changes in morphology and protein expression profile in penumbra 1 h after local photothrombotic infarction induced by laser irradiation of the cerebral cortex after Bengal Rose administration. Morphological study using standard hematoxylin/eosin staining showed a 3-mm infarct core surrounded by 1.5-2.0 mm penumbra. Morphological changes in the penumbra were lesser and decreased towards its periphery. Antibody microarrays against 224 neuronal and signaling proteins were used for proteomic study. The observed upregulation of penumbra proteins involved in maintaining neurite integrity and guidance (NAV3, MAP1, CRMP2, PMP22); intercellular interactions (N-cadherin); synaptic transmission (glutamate decarboxylase, tryptophan hydroxylase, Munc-18-1, Munc-18-3, and synphilin-1); mitochondria quality control and mitophagy (PINK1 and Parkin); ubiquitin-mediated proteolysis and tissue clearance (UCHL1, PINK1, Parkin, synphilin-1); and signaling proteins (PKBα and ERK5) could be associated with tissue recovery. Downregulation of PKC, PKCβ1/2, and TDP-43 could also reduce tissue injury. These changes in expression of some neuronal proteins were directed mainly to protection and tissue recovery in the penumbra. Some upregulated proteins might serve as markers of protection processes in a penumbra.

Finite difference time domain (FDTD) modeling of implanted deep brain stimulation electrodes and brain tissue.

PubMed

Gabran, S R I; Saad, J H; Salama, M M A; Mansour, R R

2009-01-01

This paper demonstrates the electromagnetic modeling and simulation of an implanted Medtronic deep brain stimulation (DBS) electrode using finite difference time domain (FDTD). The model is developed using Empire XCcel and represents the electrode surrounded with brain tissue assuming homogenous and isotropic medium. The model is created to study the parameters influencing the electric field distribution within the tissue in order to provide reference and benchmarking data for DBS and intra-cortical electrode development.

In vivo evaluation of needle force and friction stress during insertion at varying insertion speed into the brain.

PubMed

Casanova, Fernando; Carney, Paul R; Sarntinoranont, Malisa

2014-11-30

Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in tissue damage which can promote flowback along the needle track and improper targeting. The goal of this study was to evaluate friction stress (calculated from needle insertion force) as a measure of tissue contact and damage during needle insertion for varying insertion speeds. Forces and surface dimpling during needle insertion were measured in rat brain in vivo. Needle retraction forces were used to calculate friction stresses. These measures were compared to track damage from a previous study. Differences between brain tissues and soft hydrogels were evaluated for varying insertion speeds: 0.2, 2, and 10mm/s. In brain tissue, average insertion force and surface dimpling increased with increasing insertion speed. Average friction stress along the needle-tissue interface decreased with insertion speed (from 0.58 ± 0.27 to 0.16 ± 0.08 kPa). Friction stress varied between brain regions: cortex (0.227 ± 0.27 kPa), external capsule (0.222 ± 0.19 kPa), and CPu (0.383 ± 0.30 kPa). Hydrogels exhibited opposite trends for dimpling and friction stress with insertion speed. Previously, increasing needle damage with insertion speed has been measured with histological methods. Friction stress appears to decrease with increasing tissue damage and decreasing tissue contact, providing the potential for in vivo and real time evaluation along the needle track. Force derived friction stress decreased with increasing insertion speed and was smaller within white matter regions. Hydrogels exhibited opposite trends to brain tissue. Copyright © 2014 Elsevier B.V. All rights reserved.

Non-invasive intraoperative optical coherence tomography of the resection cavity during surgery of intrinsic brain tumors

NASA Astrophysics Data System (ADS)

Giese, A.; Böhringer, H. J.; Leppert, J.; Kantelhardt, S. R.; Lankenau, E.; Koch, P.; Birngruber, R.; Hüttmann, G.

2006-02-01

Optical coherence tomography (OCT) is a non-invasive imaging technique with a micrometer resolution. It allows non-contact / non-invasive analysis of central nervous system tissues with a penetration depth of 1-3,5 mm reaching a spatial resolution of approximately 4-15 μm. We have adapted spectral-domain OCT (SD-OCT) and time-domain OCT (TD-OCT) for intraoperative detection of residual tumor during brain tumor surgery. Human brain tumor tissue and areas of the resection cavity were analyzed during the resection of gliomas using this new technology. The site of analysis was registered using a neuronavigation system and biopsies were taken and submitted to routine histology. We have used post image acquisition processing to compensate for movements of the brain and to realign A-scan images for calculation of a light attenuation factor. OCT imaging of normal cortex and white matter showed a typical light attenuation profile. Tumor tissue depending on the cellularity of the specimen showed a loss of the normal light attenuation profile resulting in altered light attenuation coefficients compared to normal brain. Based on this parameter and the microstructure of the tumor tissue, which was entirely absent in normal tissue, OCT analysis allowed the discrimination of normal brain tissue, invaded brain, solid tumor tissue, and necrosis. Following macroscopically complete resections OCT analysis of the resection cavity displayed the typical microstructure and light attenuation profile of tumor tissue in some specimens, which in routine histology contained microscopic residual tumor tissue. We have demonstrated that this technology may be applied to the intraoperative detection of residual tumor during resection of human gliomas.

Applications of magnetic resonance image segmentation in neurology

NASA Astrophysics Data System (ADS)

Heinonen, Tomi; Lahtinen, Antti J.; Dastidar, Prasun; Ryymin, Pertti; Laarne, Paeivi; Malmivuo, Jaakko; Laasonen, Erkki; Frey, Harry; Eskola, Hannu

1999-05-01

After the introduction of digital imagin devices in medicine computerized tissue recognition and classification have become important in research and clinical applications. Segmented data can be applied among numerous research fields including volumetric analysis of particular tissues and structures, construction of anatomical modes, 3D visualization, and multimodal visualization, hence making segmentation essential in modern image analysis. In this research project several PC based software were developed in order to segment medical images, to visualize raw and segmented images in 3D, and to produce EEG brain maps in which MR images and EEG signals were integrated. The software package was tested and validated in numerous clinical research projects in hospital environment.

Zinc Signal in Brain Diseases.

PubMed

Portbury, Stuart D; Adlard, Paul A

2017-11-23

The divalent cation zinc is an integral requirement for optimal cellular processes, whereby it contributes to the function of over 300 enzymes, regulates intracellular signal transduction, and contributes to efficient synaptic transmission in the central nervous system. Given the critical role of zinc in a breadth of cellular processes, its cellular distribution and local tissue level concentrations remain tightly regulated via a series of proteins, primarily including zinc transporter and zinc import proteins. A loss of function of these regulatory pathways, or dietary alterations that result in a change in zinc homeostasis in the brain, can all lead to a myriad of pathological conditions with both acute and chronic effects on function. This review aims to highlight the role of zinc signaling in the central nervous system, where it may precipitate or potentiate diverse issues such as age-related cognitive decline, depression, Alzheimer's disease or negative outcomes following brain injury.

In Vivo Reprogramming for CNS Repair: Regenerating Neurons from Endogenous Glial Cells

PubMed Central

Li, Hedong; Chen, Gong

2017-01-01

Neuroregeneration in the central nervous system (CNS) has proven to be difficult despite decades of research. The old dogma that CNS neurons cannot be regenerated in the adult mammalian brain has been overturned; however, endogenous adult neurogenesis appears to be insufficient for brain repair. Stem cell therapy once held promise for generating large quantities of neurons in the CNS, but immunorejection and long-term functional integration remain major hurdles. In this perspective, we discuss the use of in vivo reprogramming as an emerging technology to regenerate functional neurons from endogenous glial cells inside the brain and spinal cord. Besides the CNS, in vivo reprogramming has been demonstrated successfully in the pancreas, heart and liver, and may be adopted in other organs. Although challenges remain for translating this technology into clinical therapies, we anticipate that in vivo reprogramming may revolutionize regenerative medicine by using a patient’s own internal cells for tissue repair. PMID:27537482

Enhancement of Sexual Behavior in Female Rats by Neonatal Transplantation of Brain Tissue from Males

NASA Astrophysics Data System (ADS)

Arendash, Gary W.; Gorski, Roger A.

1982-09-01

Transplantation of preoptic tissue from male rat neonates into the preoptic area of female littermates increased masculine and feminine sexual behavior in the recipients during adulthood. This suggests that functional connections develop between the transplanted neural tissue and the host brain. A new intraparenchymal brain transplantation technique was used to achieve these results.

Multimodal optical coherence tomography for in vivo imaging of brain tissue structure and microvascular network at glioblastoma

NASA Astrophysics Data System (ADS)

Yashin, Konstantin S.; Kiseleva, Elena B.; Gubarkova, Ekaterina V.; Matveev, Lev A.; Karabut, Maria M.; Elagin, Vadim V.; Sirotkina, Marina A.; Medyanik, Igor A.; Kravets, L. Y.; Gladkova, Natalia D.

2017-02-01

In the case of infiltrative brain tumors the surgeon faces difficulties in determining their boundaries to achieve total resection. The aim of the investigation was to evaluate the performance of multimodal OCT (MM OCT) for differential diagnostics of normal brain tissue and glioma using an experimental model of glioblastoma. The spectral domain OCT device that was used for the study provides simultaneously two modes: cross-polarization and microangiographic OCT. The comparative analysis of the both OCT modalities images from tumorous and normal brain tissue areas concurrently with histologic correlation shows certain difference between when accordingly to morphological and microvascular tissue features.

Influence of strain rate on indentation response of porcine brain.

PubMed

Qian, Long; Zhao, Hongwei; Guo, Yue; Li, Yuanshang; Zhou, Mingxing; Yang, Liguo; Wang, Zhiwei; Sun, Yifan

2018-06-01

Knowledge of brain tissue mechanical properties may be critical for formulating hypotheses about some specific diseases mechanisms and its accurate simulations such as traumatic brain injury (TBI) and tumor growth. Compared to traditional tests (e.g. tensile and compression), indentation shows superiority by virtue of its pinpoint and nondestructive/quasi-nondestructive. As a viscoelastic material, the properties of brain tissue depend on the strain rate by definition. However most efforts focus on the aspect of velocity in the field of brain indentation, rather than strain rate. The influence of strain rate on indentation response of brain tissue is taken little attention. Further, by comparing different results from literatures, it is also obvious that strain rate rather than velocity is more appropriate to characterize mechanical properties of brain. In this paper, to systematically characterize the influence of strain rate, a series of indentation-relaxation tests n = 210) are performed on the cortex of porcine brain using a custom-designed indentation device. The mechanical response that correlates with indenter diameters, depths of indentation and velocities, is revealed for the indentation portion, and elastic behavior of brain tissue is analyzed as the function of strain rate. Similarly, a linear viscoelastic model with a Prony series is employed for the indentation-relaxation portion, wherein the brain tissue shows more viscous and responds more quickly with increasing strain rate. Understanding the effect of strain rate on mechanical properties of brain indentation may be far-reaching for brain injury biomechanics and accurate simulations, but be important for bridging between indentation results of different literatures. Copyright © 2018 Elsevier Ltd. All rights reserved.

Preoperative magnetic resonance and intraoperative ultrasound fusion imaging for real-time neuronavigation in brain tumor surgery.

PubMed

Prada, F; Del Bene, M; Mattei, L; Lodigiani, L; DeBeni, S; Kolev, V; Vetrano, I; Solbiati, L; Sakas, G; DiMeco, F

2015-04-01

Brain shift and tissue deformation during surgery for intracranial lesions are the main actual limitations of neuro-navigation (NN), which currently relies mainly on preoperative imaging. Ultrasound (US), being a real-time imaging modality, is becoming progressively more widespread during neurosurgical procedures, but most neurosurgeons, trained on axial computed tomography (CT) and magnetic resonance imaging (MRI) slices, lack specific US training and have difficulties recognizing anatomic structures with the same confidence as in preoperative imaging. Therefore real-time intraoperative fusion imaging (FI) between preoperative imaging and intraoperative ultrasound (ioUS) for virtual navigation (VN) is highly desirable. We describe our procedure for real-time navigation during surgery for different cerebral lesions. We performed fusion imaging with virtual navigation for patients undergoing surgery for brain lesion removal using an ultrasound-based real-time neuro-navigation system that fuses intraoperative cerebral ultrasound with preoperative MRI and simultaneously displays an MRI slice coplanar to an ioUS image. 58 patients underwent surgery at our institution for intracranial lesion removal with image guidance using a US system equipped with fusion imaging for neuro-navigation. In all cases the initial (external) registration error obtained by the corresponding anatomical landmark procedure was below 2 mm and the craniotomy was correctly placed. The transdural window gave satisfactory US image quality and the lesion was always detectable and measurable on both axes. Brain shift/deformation correction has been successfully employed in 42 cases to restore the co-registration during surgery. The accuracy of ioUS/MRI fusion/overlapping was confirmed intraoperatively under direct visualization of anatomic landmarks and the error was < 3 mm in all cases (100 %). Neuro-navigation using intraoperative US integrated with preoperative MRI is reliable, accurate and user-friendly. Moreover, the adjustments are very helpful in correcting brain shift and tissue distortion. This integrated system allows true real-time feedback during surgery and is less expensive and time-consuming than other intraoperative imaging techniques, offering high precision and orientation. © Georg Thieme Verlag KG Stuttgart · New York.

Lesion-induced increase in survival and migration of human neural progenitor cells releasing GDNF

PubMed Central

Behrstock, Soshana; Ebert, Allison D.; Klein, Sandra; Schmitt, Melanie; Moore, Jeannette M.; Svendsen, Clive N.

2009-01-01

The use of human neural progenitor cells (hNPC) has been proposed to provide neuronal replacement or astrocytes delivering growth factors for brain disorders such as Parkinson’s and Huntington’s disease. Success in such studies likely requires migration from the site of transplantation and integration into host tissue in the face of ongoing damage. In the current study, hNPC modified to release glial cell line derived neurotrophic factor (hNPCGDNF) were transplanted into either intact or lesioned animals. GDNF release itself had no effect on the survival, migration or differentiation of the cells. The most robust migration and survival was found using a direct lesion of striatum (Huntington’s model) with indirect lesions of the dopamine system (Parkinson’s model) or intact animals showing successively less migration and survival. No lesion affected differentiation patterns. We conclude that the type of brain injury dictates migration and integration of hNPC which has important consequences when considering transplantation of these cells as a therapy for neurodegenerative diseases. PMID:19044202

EDITORIAL: Focus on the neural interface Focus on the neural interface

NASA Astrophysics Data System (ADS)

Durand, Dominique M.

2009-10-01

The possibility of an effective connection between neural tissue and computers has inspired scientists and engineers to develop new ways of controlling and obtaining information from the nervous system. These applications range from `brain hacking' to neural control of artificial limbs with brain signals. Notwithstanding the significant advances in neural prosthetics in the last few decades and the success of some stimulation devices such as cochlear prosthesis, neurotechnology remains below its potential for restoring neural function in patients with nervous system disorders. One of the reasons for this limited impact can be found at the neural interface and close attention to the integration between electrodes and tissue should improve the possibility of successful outcomes. The neural interfaces research community consists of investigators working in areas such as deep brain stimulation, functional neuromuscular/electrical stimulation, auditory prostheses, cortical prostheses, neuromodulation, microelectrode array technology, brain-computer/machine interfaces. Following the success of previous neuroprostheses and neural interfaces workshops, funding (from NIH) was obtained to establish a biennial conference in the area of neural interfaces. The first Neural Interfaces Conference took place in Cleveland, OH in 2008 and several topics from this conference have been selected for publication in this special section of the Journal of Neural Engineering. Three `perspectives' review the areas of neural regeneration (Corredor and Goldberg), cochlear implants (O'Leary et al) and neural prostheses (Anderson). Seven articles focus on various aspects of neural interfacing. One of the most popular of these areas is the field of brain-computer interfaces. Fraser et al, report on a method to generate robust control with simple signal processing algorithms of signals obtained with electrodes implanted in the brain. One problem with implanted electrode arrays, however, is that they can fail to record reliably neural signals for long periods of time. McConnell et al show that by measuring the impedance of the tissue, one can evaluate the extent of the tissue response to the presence of the electrode. Another problem with the neural interface is the mismatch of the mechanical properties between electrode and tissue. Basinger et al use finite element modeling to analyze this mismatch in retinal prostheses and guide the design of new implantable devices. Electrical stimulation has been the method of choice to activate externally the nervous system. However, Zhang et al show that a novel dual hybrid device integrating electrical and optical stimulation can provide an effective interface for simultaneous recording and stimulation. By interfacing an EMG recording system and a movement detection system, Johnson and Fuglevand develop a model capable of predicting muscle activity during movement that could be important for the development of motor prostheses. Sensory restoration is another unsolved problem in neural prostheses. By developing a novel interface between the dorsal root ganglia and electrodes arrays, Gaunt et al show that it is possible to recruit afferent fibers for sensory substitution. Finally, by interfacing directly with muscles, Jung and colleagues show that stimulation of muscles involved in locomotion following spinal cord damage in rats can provide an effective treatment modality for incomplete spinal cord injury. This series of articles clearly shows that the interface is indeed one of the keys to successful therapeutic neural devices. The next Neural Interfaces Conference will take place in Los Angeles, CA in June 2010 and one can expect to see new developments in neural engineering obtained by focusing on the neural interface.

Near infrared Raman spectra of human brain lipids

NASA Astrophysics Data System (ADS)

Krafft, Christoph; Neudert, Lars; Simat, Thomas; Salzer, Reiner

2005-05-01

Human brain tissue, in particular white matter, contains high lipid content. These brain lipids can be divided into three principal classes: neutral lipids including the steroid cholesterol, phospholipids and sphingolipids. Major lipids in normal human brain tissue are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, sphingomyelin, galactocerebrosides, gangliosides, sulfatides and cholesterol. Minor lipids are cholesterolester and triacylglycerides. During transformation from normal brain tissue to tumors, composition and concentration of lipids change in a specific way. Therefore, analysis of lipids might be used as a diagnostic parameter to distinguish normal tissue from tumors and to determine the tumor type and tumor grade. Raman spectroscopy has been suggested as an analytical tool to detect these changes even under intra-operative conditions. We recorded Raman spectra of the 12 major and minor brain lipids with 785 nm excitation in order to identify their spectral fingerprints for qualitative and quantitative analyses.

A wireless beta-microprobe based on pixelated silicon for in vivo brain studies in freely moving rats

NASA Astrophysics Data System (ADS)

Märk, J.; Benoit, D.; Balasse, L.; Benoit, M.; Clémens, J. C.; Fieux, S.; Fougeron, D.; Graber-Bolis, J.; Janvier, B.; Jevaud, M.; Genoux, A.; Gisquet-Verrier, P.; Menouni, M.; Pain, F.; Pinot, L.; Tourvielle, C.; Zimmer, L.; Morel, C.; Laniece, P.

2013-07-01

The investigation of neurophysiological mechanisms underlying the functional specificity of brain regions requires the development of technologies that are well adjusted to in vivo studies in small animals. An exciting challenge remains the combination of brain imaging and behavioural studies, which associates molecular processes of neuronal communications to their related actions. A pixelated intracerebral probe (PIXSIC) presents a novel strategy using a submillimetric probe for beta+ radiotracer detection based on a pixelated silicon diode that can be stereotaxically implanted in the brain region of interest. This fully autonomous detection system permits time-resolved high sensitivity measurements of radiotracers with additional imaging features in freely moving rats. An application-specific integrated circuit (ASIC) allows for parallel signal processing of each pixel and enables the wireless operation. All components of the detector were tested and characterized. The beta+ sensitivity of the system was determined with the probe dipped into radiotracer solutions. Monte Carlo simulations served to validate the experimental values and assess the contribution of gamma noise. Preliminary implantation tests on anaesthetized rats proved PIXSIC's functionality in brain tissue. High spatial resolution allows for the visualization of radiotracer concentration in different brain regions with high temporal resolution.

Fingolimod inhibits brain atrophy and promotes brain-derived neurotrophic factor in an animal model of multiple sclerosis.

PubMed

Smith, Paul A; Schmid, Cindy; Zurbruegg, Stefan; Jivkov, Magali; Doelemeyer, Arno; Theil, Diethilde; Dubost, Valérie; Beckmann, Nicolau

2018-05-15

Longitudinal brain atrophy quantification is a critical efficacy measurement in multiple sclerosis (MS) clinical trials and the determination of No Evidence of Disease Activity (NEDA). Utilising fingolimod as a clinically validated therapy we evaluated the use of repeated brain tissue volume measures during chronic experimental autoimmune encephalomyelitis (EAE) as a new preclinical efficacy measure. Brain volume changes were quantified using magnetic resonance imaging (MRI) at 7 Tesla and correlated to treatment-induced brain derived neurotrophic factor (BDNF) measured in blood, cerebrospinal fluid, spinal cord and brain. Serial brain MRI measurements revealed slow progressive brain volume loss in vehicle treated EAE mice despite a stable clinical score. Fingolimod (1 mg/kg) significantly ameliorated brain tissue atrophy in the cerebellum and striatum when administered from established EAE disease onwards. Fingolimod-dependent tissue preservation was associated with induction of BDNF specifically within the brain and co-localized with neuronal soma. In contrast, therapeutic teriflunomide (3 mg/kg) treatment failed to inhibit CNS autoimmune mediated brain degeneration. Finally, weekly anti-IL-17A antibody (15 mg/kg) treatment was highly efficacious and preserved whole brain, cerebellum and striatum volume. Fingolimod-mediated BDNF increases within the CNS may contribute to limiting progressive tissue loss during chronic neuroinflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

Development and characterization of a handheld hyperspectral Raman imaging probe system for molecular characterization of tissue on mesoscopic scales.

PubMed

St-Arnaud, Karl; Aubertin, Kelly; Strupler, Mathias; Madore, Wendy-Julie; Grosset, Andrée-Anne; Petrecca, Kevin; Trudel, Dominique; Leblond, Frédéric

2018-01-01

Raman spectroscopy is a promising cancer detection technique for surgical guidance applications. It can provide quantitative information relating to global tissue properties associated with structural, metabolic, immunological, and genetic biochemical phenomena in terms of molecular species including amino acids, lipids, proteins, and nucleic acid (DNA). To date in vivo Raman spectroscopy systems mostly included probes and biopsy needles typically limited to single-point tissue interrogation over a scale between 100 and 500 microns. The development of wider field handheld systems could improve tumor localization for a range of open surgery applications including brain, ovarian, and skin cancers. Here we present a novel Raman spectroscopy implementation using a coherent imaging bundle of fibers to create a probe capable of reconstructing molecular images over mesoscopic fields of view. Detection is performed using linear scanning with a rotation mirror and an imaging spectrometer. Different slits widths were tested at the entrance of the spectrometer to optimize spatial and spectral resolution while preserving sufficient signal-to-noise ratios to detect the principal Raman tissue features. The nonbiological samples, calcite and polytetrafluoroethylene (PTFE), were used to characterize the performance of the system. The new wide-field probe was tested on ex vivo samples of calf brain and swine tissue. Raman spectral content of both tissue types were validated with data from the literature and compared with data acquired with a single-point Raman spectroscopy probe. The single-point probe was used as the gold standard against which the new instrument was benchmarked as it has already been thoroughly validated for biological tissue characterization. We have developed and characterized a practical noncontact handheld Raman imager providing tissue information at a spatial resolution of 115 microns over a field of view >14 mm 2 and a spectral resolution of 6 cm -1 over the whole fingerprint region. Typical integration time to acquire an entire Raman image over swine tissue was set to approximately 100 s. Spectra acquired with both probes (single-point and wide-field) showed good agreement, with a Pearson correlation factor >0.85 over different tissue categories. Protein and lipid content of imaged tissue were manifested into the measured spectra which correlated well with previous findings in the literature. An example of quantitative molecular map is presented for swine tissue and calf brain based on the ratio of protein-to-lipid content showing clear delineations between white and gray matter as well as between adipose and muscle tissue. We presented the development of a Raman imaging probe with a field of view of a few millimeters and a spatial resolution consistent with standard surgical imaging methods using an imaging bundle. Spectra acquired with the newly developed system on swine tissue and calf brain correlated well with an establish single-point probe and observed spectral features agreed with previous finding in the literature. The imaging probe has demonstrated its ability to reconstruct molecular images of soft tissues. The approach presented here has a lot of potential for the development of surgical Raman imaging probe to guide the surgeon during cancer surgery. © 2017 American Association of Physicists in Medicine.

Multi-timescale modeling of activity-dependent metabolic coupling in the neuron-glia-vasculature ensemble.

PubMed

Jolivet, Renaud; Coggan, Jay S; Allaman, Igor; Magistretti, Pierre J

2015-02-01

Glucose is the main energy substrate in the adult brain under normal conditions. Accumulating evidence, however, indicates that lactate produced in astrocytes (a type of glial cell) can also fuel neuronal activity. The quantitative aspects of this so-called astrocyte-neuron lactate shuttle (ANLS) are still debated. To address this question, we developed a detailed biophysical model of the brain's metabolic interactions. Our model integrates three modeling approaches, the Buxton-Wang model of vascular dynamics, the Hodgkin-Huxley formulation of neuronal membrane excitability and a biophysical model of metabolic pathways. This approach provides a template for large-scale simulations of the neuron-glia-vasculature (NGV) ensemble, and for the first time integrates the respective timescales at which energy metabolism and neuronal excitability occur. The model is constrained by relative neuronal and astrocytic oxygen and glucose utilization, by the concentration of metabolites at rest and by the temporal dynamics of NADH upon activation. These constraints produced four observations. First, a transfer of lactate from astrocytes to neurons emerged in response to activity. Second, constrained by activity-dependent NADH transients, neuronal oxidative metabolism increased first upon activation with a subsequent delayed astrocytic glycolysis increase. Third, the model correctly predicted the dynamics of extracellular lactate and oxygen as observed in vivo in rats. Fourth, the model correctly predicted the temporal dynamics of tissue lactate, of tissue glucose and oxygen consumption, and of the BOLD signal as reported in human studies. These findings not only support the ANLS hypothesis but also provide a quantitative mathematical description of the metabolic activation in neurons and glial cells, as well as of the macroscopic measurements obtained during brain imaging.

Calcium Dysregulation and Homeostasis of Neural Calcium in the Molecular Mechanisms of Neurodegenerative Diseases Provide Multiple Targets for Neuroprotection

PubMed Central

Zündorf, Gregor

2011-01-01

Abstract The intracellular free calcium concentration subserves complex signaling roles in brain. Calcium cations (Ca2+) regulate neuronal plasticity underlying learning and memory and neuronal survival. Homo- and heterocellular control of Ca2+ homeostasis supports brain physiology maintaining neural integrity. Ca2+ fluxes across the plasma membrane and between intracellular organelles and compartments integrate diverse cellular functions. A vast array of checkpoints controls Ca2+, like G protein-coupled receptors, ion channels, Ca2+ binding proteins, transcriptional networks, and ion exchangers, in both the plasma membrane and the membranes of mitochondria and endoplasmic reticulum. Interactions between Ca2+ and reactive oxygen species signaling coordinate signaling, which can be either beneficial or detrimental. In neurodegenerative disorders, cellular Ca2+-regulating systems are compromised. Oxidative stress, perturbed energy metabolism, and alterations of disease-related proteins result in Ca2+-dependent synaptic dysfunction, impaired plasticity, and neuronal demise. We review Ca2+ control processes relevant for physiological and pathophysiological conditions in brain tissue. Dysregulation of Ca2+ is decisive for brain cell death and degeneration after ischemic stroke, long-term neurodegeneration in Alzheimer's disease, Parkinson's disease, Huntington's disease, inflammatory processes, such as in multiple sclerosis, epileptic sclerosis, and leucodystrophies. Understanding the underlying molecular processes is of critical importance for the development of novel therapeutic strategies to prevent neurodegeneration and confer neuroprotection. Antioxid. Redox Signal. 14, 1275–1288. PMID:20615073

Lesion registration for longitudinal disease tracking in an imaging informatics-based multiple sclerosis eFolder

NASA Astrophysics Data System (ADS)

Ma, Kevin; Liu, Joseph; Zhang, Xuejun; Lerner, Alex; Shiroishi, Mark; Amezcua, Lilyana; Liu, Brent

2016-03-01

We have designed and developed a multiple sclerosis eFolder system for patient data storage, image viewing, and automatic lesion quantification results stored in DICOM-SR format. The web-based system aims to be integrated in DICOM-compliant clinical and research environments to aid clinicians in patient treatments and data analysis. The system needs to quantify lesion volumes, identify and register lesion locations to track shifts in volume and quantity of lesions in a longitudinal study. In order to perform lesion registration, we have developed a brain warping and normalizing methodology using Statistical Parametric Mapping (SPM) MATLAB toolkit for brain MRI. Patients' brain MR images are processed via SPM's normalization processes, and the brain images are analyzed and warped according to the tissue probability map. Lesion identification and contouring are completed by neuroradiologists, and lesion volume quantification is completed by the eFolder's CAD program. Lesion comparison results in longitudinal studies show key growth and active regions. The results display successful lesion registration and tracking over a longitudinal study. Lesion change results are graphically represented in the web-based user interface, and users are able to correlate patient progress and changes in the MRI images. The completed lesion and disease tracking tool would enable the eFolder to provide complete patient profiles, improve the efficiency of patient care, and perform comprehensive data analysis through an integrated imaging informatics system.

Quantifying structural alterations in Alzheimer's disease brains using quantitative phase imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lee, Moosung; Lee, Eeksung; Jung, JaeHwang; Yu, Hyeonseung; Kim, Kyoohyun; Yoon, Jonghee; Lee, Shinhwa; Jeong, Yong; Park, YongKeun

2017-02-01

Imaging brain tissues is an essential part of neuroscience because understanding brain structure provides relevant information about brain functions and alterations associated with diseases. Magnetic resonance imaging and positron emission tomography exemplify conventional brain imaging tools, but these techniques suffer from low spatial resolution around 100 μm. As a complementary method, histopathology has been utilized with the development of optical microscopy. The traditional method provides the structural information about biological tissues to cellular scales, but relies on labor-intensive staining procedures. With the advances of illumination sources, label-free imaging techniques based on nonlinear interactions, such as multiphoton excitations and Raman scattering, have been applied to molecule-specific histopathology. Nevertheless, these techniques provide limited qualitative information and require a pulsed laser, which is difficult to use for pathologists with no laser training. Here, we present a label-free optical imaging of mouse brain tissues for addressing structural alteration in Alzheimer's disease. To achieve the mesoscopic, unlabeled tissue images with high contrast and sub-micrometer lateral resolution, we employed holographic microscopy and an automated scanning platform. From the acquired hologram of the brain tissues, we could retrieve scattering coefficients and anisotropies according to the modified scattering-phase theorem. This label-free imaging technique enabled direct access to structural information throughout the tissues with a sub-micrometer lateral resolution and presented a unique means to investigate the structural changes in the optical properties of biological tissues.

In vivo mapping of current density distribution in brain tissues during deep brain stimulation (DBS)

NASA Astrophysics Data System (ADS)

Sajib, Saurav Z. K.; Oh, Tong In; Kim, Hyung Joong; Kwon, Oh In; Woo, Eung Je

2017-01-01

New methods for in vivo mapping of brain responses during deep brain stimulation (DBS) are indispensable to secure clinical applications. Assessment of current density distribution, induced by internally injected currents, may provide an alternative method for understanding the therapeutic effects of electrical stimulation. The current flow and pathway are affected by internal conductivity, and can be imaged using magnetic resonance-based conductivity imaging methods. Magnetic resonance electrical impedance tomography (MREIT) is an imaging method that can enable highly resolved mapping of electromagnetic tissue properties such as current density and conductivity of living tissues. In the current study, we experimentally imaged current density distribution of in vivo canine brains by applying MREIT to electrical stimulation. The current density maps of three canine brains were calculated from the measured magnetic flux density data. The absolute current density values of brain tissues, including gray matter, white matter, and cerebrospinal fluid were compared to assess the active regions during DBS. The resulting current density in different tissue types may provide useful information about current pathways and volume activation for adjusting surgical planning and understanding the therapeutic effects of DBS.

Effects of positive end-expiratory pressure on brain tissue oxygen pressure of severe traumatic brain injury patients with acute respiratory distress syndrome: A pilot study.

PubMed

Nemer, Sérgio Nogueira; Caldeira, Jefferson B; Santos, Ricardo G; Guimarães, Bruno L; Garcia, João Márcio; Prado, Darwin; Silva, Ricardo T; Azeredo, Leandro M; Faria, Eduardo R; Souza, Paulo Cesar P

2015-12-01

To verify whether high positive end-expiratory pressure levels can increase brain tissue oxygen pressure, and also their effects on pulse oxygen saturation, intracranial pressure, and cerebral perfusion pressure. Twenty traumatic brain injury patients with acute respiratory distress syndrome were submitted to positive end-expiratory pressure levels of 5, 10, and 15 cm H2O progressively. The 3 positive end-expiratory pressure levels were used during 20 minutes for each one, whereas brain tissue oxygen pressure, oxygen saturation, intracranial pressure, and cerebral perfusion pressure were recorded. Brain tissue oxygen pressure and oxygen saturation increased significantly with increasing positive end-expiratory pressure from 5 to 10 and from 10 to 15 cm H2O (P=.0001 and P=.0001 respectively). Intracranial pressure and cerebral perfusion pressure did not differ significantly with increasing positive end-expiratory pressure from 5 to 10 and from 10 to 15 cm H2O (P=.16 and P=.79 respectively). High positive end-expiratory pressure levels increased brain tissue oxygen pressure and oxygen saturation, without increase in intracranial pressure or decrease in cerebral perfusion pressure. High positive end-expiratory pressure levels can be used in severe traumatic brain injury patients with acute respiratory distress syndrome as a safe alternative to improve brain oxygenation. Copyright © 2015 Elsevier Inc. All rights reserved.

Pharmacokinetics and brain penetration of carbapenems in mice.

PubMed

Matsumoto, Kazuaki; Kurihara, Yuji; Kuroda, Yuko; Hori, Seiji; Kizu, Junko

2016-05-01

An adverse effect associated with the administration of carbapenems is central nervous system (CNS) toxicity, with higher brain concentrations of carbapenems being linked to an increased risk of seizures. However, the pharmacokinetics and brain penetration of carbapenems have not yet been examined. Thus, the aim of this in vivo investigation was to determine the pharmacokinetics and brain penetration of carbapenems in mice. Blood samples and brain tissue samples were obtained 10, 20, 30, 60, and 120 min after the subcutaneous administration of carbapenems (91 mg/kg). We obtained the following values for the pharmacokinetic parameters of carbapenems in mice: 1.20-1.71 L/h/kg for CLtotal/F, 1.41-2.03 h(-1) for Ke, 0.34-0.51 h for T1/2, 0.66-0.95 L/kg for Vss/F, 0.49-0.73 h for MRT, 83.46-110.58 μg/mL for Cmax, plasma, and 0.28-0.83 μg/g for Cmax, brain tissue. The AUC0-∞ of the carbapenems tested in plasma were in the following order: doripenem > meropenem > biapenem > imipenem, and in brain tissue were: imipenem > doripenem > meropenem > biapenem. The degrees of brain tissue penetration, defined as the AUC0-∞, brain tissue/fAUC0-∞, plasma ratio, were 0.016 for imipenem, 0.004 for meropenem, 0.002 for biapenem, and 0.008 for doripenem. The results of the present study demonstrated that, of the carbapenems examined, imipenem penetrated brain tissue to the greatest extent. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research.

PubMed

Walton, Esther; Hass, Johanna; Liu, Jingyu; Roffman, Joshua L; Bernardoni, Fabio; Roessner, Veit; Kirsch, Matthias; Schackert, Gabriele; Calhoun, Vince; Ehrlich, Stefan

2016-03-01

Given the difficulty of procuring human brain tissue, a key question in molecular psychiatry concerns the extent to which epigenetic signatures measured in more accessible tissues such as blood can serve as a surrogate marker for the brain. Here, we aimed (1) to investigate the blood-brain correspondence of DNA methylation using a within-subject design and (2) to identify changes in DNA methylation of brain-related biological pathways in schizophrenia.We obtained paired blood and temporal lobe biopsy samples simultaneously from 12 epilepsy patients during neurosurgical treatment. Using the Infinium 450K methylation array we calculated similarity of blood and brain DNA methylation for each individual separately. We applied our findings by performing gene set enrichment analyses (GSEA) of peripheral blood DNA methylation data (Infinium 27K) of 111 schizophrenia patients and 122 healthy controls and included only Cytosine-phosphate-Guanine (CpG) sites that were significantly correlated across tissues.Only 7.9% of CpG sites showed a statistically significant, large correlation between blood and brain tissue, a proportion that although small was significantly greater than predicted by chance. GSEA analysis of schizophrenia data revealed altered methylation profiles in pathways related to precursor metabolites and signaling peptides.Our findings indicate that most DNA methylation markers in peripheral blood do not reliably predict brain DNA methylation status. However, a subset of peripheral data may proxy methylation status of brain tissue. Restricting the analysis to these markers can identify meaningful epigenetic differences in schizophrenia and potentially other brain disorders. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Predicting Intracranial Pressure and Brain Tissue Oxygen Crises in Patients With Severe Traumatic Brain Injury.

PubMed

Myers, Risa B; Lazaridis, Christos; Jermaine, Christopher M; Robertson, Claudia S; Rusin, Craig G

2016-09-01

To develop computer algorithms that can recognize physiologic patterns in traumatic brain injury patients that occur in advance of intracranial pressure and partial brain tissue oxygenation crises. The automated early detection of crisis precursors can provide clinicians with time to intervene in order to prevent or mitigate secondary brain injury. A retrospective study was conducted from prospectively collected physiologic data. intracranial pressure, and partial brain tissue oxygenation crisis events were defined as intracranial pressure of greater than or equal to 20 mm Hg lasting at least 15 minutes and partial brain tissue oxygenation value of less than 10 mm Hg for at least 10 minutes, respectively. The physiologic data preceding each crisis event were used to identify precursors associated with crisis onset. Multivariate classification models were applied to recorded data in 30-minute epochs of time to predict crises between 15 and 360 minutes in the future. The neurosurgical unit of Ben Taub Hospital (Houston, TX). Our cohort consisted of 817 subjects with severe traumatic brain injury. Our algorithm can predict the onset of intracranial pressure crises with 30-minute advance warning with an area under the receiver operating characteristic curve of 0.86 using only intracranial pressure measurements and time since last crisis. An analogous algorithm can predict the start of partial brain tissue oxygenation crises with 30-minute advanced warning with an area under the receiver operating characteristic curve of 0.91. Our algorithms provide accurate and timely predictions of intracranial hypertension and tissue hypoxia crises in patients with severe traumatic brain injury. Almost all of the information needed to predict the onset of these events is contained within the signal of interest and the time since last crisis.

Detection of Human Brain Cancer Infiltration ex vivo and in vivo Using Quantitative Optical Coherence Tomography*

PubMed Central

Kut, Carmen; Chaichana, Kaisorn L.; Xi, Jiefeng; Raza, Shaan M.; Ye, Xiaobu; McVeigh, Elliot R.; Rodriguez, Fausto J.; Quinones-Hinojosa, Alfredo; Li, Xingde

2015-01-01

More complete brain cancer resection can prolong survival and delay recurrence. However, it is challenging to distinguish cancer from non-cancer tissues intraoperatively, especially at the transitional, infiltrative zones. This is especially critical in eloquent regions (e.g. speech and motor areas). This study tested the feasibility of label-free, quantitative optical coherence tomography (OCT) for differentiating cancer from non-cancer in human brain tissues. Fresh ex vivo human brain tissues were obtained from 32 patients with grades II-IV brain cancer and 5 patients with non-cancer brain pathologies. Based on volumetric OCT imaging data, pathologically confirmed brain cancer tissues (both high-grade and low-grade) had significantly lower optical attenuation values at both cancer core and infiltrated zones when compared with non-cancer white matter, and OCT achieved high sensitivity and specificity at an attenuation threshold of 5.5 mm-1 for brain cancer patients. We also used this attenuation threshold to confirm the intraoperative feasibility of performing in vivo OCT-guided surgery using a murine model harboring human brain cancer. Our OCT system was capable of processing and displaying a color-coded optical property map in real time at a rate of 110-215 frames per second, or 1.2-2.4 seconds for an 8-16 mm3 tissue volume, thus providing direct visual cues for cancer versus non-cancer areas. Our study demonstrates the translational and practical potential of OCT in differentiating cancer from non-cancer tissue. Its intraoperative use may facilitate safe and extensive resection of infiltrative brain cancers and consequently lead to improved outcomes when compared with current clinical standards. PMID:26084803

Arctigenin Treatment Protects against Brain Damage through an Anti-Inflammatory and Anti-Apoptotic Mechanism after Needle Insertion

PubMed Central

Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-feng; Kong, Liang; Yao, Ying-Jia; Jiao, Ya-Nan; Yan, Yu-Hui; Li, Shao-Heng; Tao, Zhen-Yu; Lian, Guan; Yang, Jing-Xian; Kang, Ting-Guo

2016-01-01

Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in a stab wound injury (SWI). Subsequent secondary injury involves the release of inflammatory and apoptotic cytokines, which have dramatic consequences on the integrity of damaged tissue, leading to the evolution of a pericontusional-damaged area minutes to days after in the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary brain injury and the determination of the underlying mechanism of action in a mouse model of SWI that mimics the process of CED. After CED, mice received a gavage of ARC from 30 min to 14 days. Neurological severity scores (NSS) and wound closure degree were assessed after the injury. Histological analysis and immunocytochemistry were used to evaluated the extent of brain damage and neuroinflammation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect universal apoptosis. Enzyme-linked immunosorbent assays (ELISA) was used to test the inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10) and lactate dehydrogenase (LDH) content. Gene levels of inflammation (TNF-α, IL-6, and IL-10) and apoptosis (Caspase-3, Bax and Bcl-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR). Using these, we analyzed ARC’s efficacy and mechanism of action. Results: ARC treatment improved neurological function by reducing brain water content and hematoma and accelerating wound closure relative to untreated mice. ARC treatment reduced the levels of TNF-α and IL-6 and the number of allograft inflammatory factor (IBA)- and myeloperoxidase (MPO)-positive cells and increased the levels of IL-10. ARC-treated mice had fewer TUNEL+ apoptotic neurons and activated caspase-3-positive neurons surrounding the lesion than controls, indicating increased neuronal survival. Conclusions: ARC treatment confers neuroprotection of brain tissue through anti-inflammatory and anti-apoptotic effects in a mouse model of SWI. These results suggest a new strategy for promoting neuronal survival and function after CED to improve long-term patient outcome. PMID:27445818

Optical coherence tomography visualizes neurons in human entorhinal cortex

PubMed Central

Magnain, Caroline; Augustinack, Jean C.; Konukoglu, Ender; Frosch, Matthew P.; Sakadžić, Sava; Varjabedian, Ani; Garcia, Nathalie; Wedeen, Van J.; Boas, David A.; Fischl, Bruce

2015-01-01

Abstract. The cytoarchitecture of the human brain is of great interest in diverse fields: neuroanatomy, neurology, neuroscience, and neuropathology. Traditional histology is a method that has been historically used to assess cell and fiber content in the ex vivo human brain. However, this technique suffers from significant distortions. We used a previously demonstrated optical coherence microscopy technique to image individual neurons in several square millimeters of en-face tissue blocks from layer II of the human entorhinal cortex, over 50  μm in depth. The same slices were then sectioned and stained for Nissl substance. We registered the optical coherence tomography (OCT) images with the corresponding Nissl stained slices using a nonlinear transformation. The neurons were then segmented in both images and we quantified the overlap. We show that OCT images contain information about neurons that is comparable to what can be obtained from Nissl staining, and thus can be used to assess the cytoarchitecture of the ex vivo human brain with minimal distortion. With the future integration of a vibratome into the OCT imaging rig, this technique can be scaled up to obtain undistorted volumetric data of centimeter cube tissue blocks in the near term, and entire human hemispheres in the future. PMID:25741528

Extracellular Nucleotides in Exercise: Possible Effect on Brain Metabolism.

ERIC Educational Resources Information Center

Forrester, Tom

1979-01-01

A review of experiments which demonstrate the release of ATP from skeletal muscle, cardiac muscle, and active brain tissue. Effects of exogenously applied ATP to brain tissue are discussed in relation to whole body exercise. (Author/SA)

Radiobiological and treatment planning study of a simultaneously integrated boost for canine nasal tumors using helical tomotherapy.

PubMed

Gutíerrez, Alonso N; Deveau, Michael; Forrest, Lisa J; Tomé, Wolfgang A; Mackie, Thomas R

2007-01-01

Feasibility of delivering a simultaneously integrated boost to canine nasal tumors using helical tomotherapy to improve tumor control probability (TCP) via an increase in total biological equivalent uniform dose (EUD) was evaluated. Eight dogs with varying size nasal tumors (5.8-110.9 cc) were replanned to 42 Gy to the nasal cavity and integrated dose boosts to gross disease of 45.2, 48.3, and 51.3 Gy in 10 fractions. EUD values were calculated for tumors and mean normalized total doses (NTD(mean)) for organs at risk (OAR). Normal Tissue Complication Probability (NTCP) values were obtained for OARs, and estimated TCP values were computed using a logistic dose-response model and based on deliverable EUD boost doses. Significant increases in estimated TCP to 54%, 74%, and 86% can be achieved with 10%, 23%, and 37% mean relative EUD boosts to the gross disease, respectively. NTCP values for blindness of either eye and for brain necrosis were < 0.01% for all boosts. Values for cataract development were 31%, 42%, and 46% for studied boost schemas, respectively. Average NTD(mean) to eyes and brain for mean EUD boosts were 10.2, 11.3, and 12.1 Gy3, and 7.5, 7.2, and 7.9 Gy2, respectively. Using helical tomotherapy, simultaneously integrated dose boosts can be delivered to increase the estimated TCP at 1-year without significantly increasing the NTD(mean) to eyes and brain. Delivery of these treatments in a prospective trial may allow quantification of a dose-response relationship in canine nasal tumors.

Modeling Brain Dynamics in Brain Tumor Patients Using the Virtual Brain.

PubMed

Aerts, Hannelore; Schirner, Michael; Jeurissen, Ben; Van Roost, Dirk; Achten, Eric; Ritter, Petra; Marinazzo, Daniele

2018-01-01

Presurgical planning for brain tumor resection aims at delineating eloquent tissue in the vicinity of the lesion to spare during surgery. To this end, noninvasive neuroimaging techniques such as functional MRI and diffusion-weighted imaging fiber tracking are currently employed. However, taking into account this information is often still insufficient, as the complex nonlinear dynamics of the brain impede straightforward prediction of functional outcome after surgical intervention. Large-scale brain network modeling carries the potential to bridge this gap by integrating neuroimaging data with biophysically based models to predict collective brain dynamics. As a first step in this direction, an appropriate computational model has to be selected, after which suitable model parameter values have to be determined. To this end, we simulated large-scale brain dynamics in 25 human brain tumor patients and 11 human control participants using The Virtual Brain, an open-source neuroinformatics platform. Local and global model parameters of the Reduced Wong-Wang model were individually optimized and compared between brain tumor patients and control subjects. In addition, the relationship between model parameters and structural network topology and cognitive performance was assessed. Results showed (1) significantly improved prediction accuracy of individual functional connectivity when using individually optimized model parameters; (2) local model parameters that can differentiate between regions directly affected by a tumor, regions distant from a tumor, and regions in a healthy brain; and (3) interesting associations between individually optimized model parameters and structural network topology and cognitive performance.

Novel Passive Clearing Methods for the Rapid Production of Optical Transparency in Whole CNS Tissue.

PubMed

Woo, Jiwon; Lee, Eunice Yoojin; Park, Hyo-Suk; Park, Jeong Yoon; Cho, Yong Eun

2018-05-08

Since the development of CLARITY, a bioelectrochemical clearing technique that allows for three-dimensional phenotype mapping within transparent tissues, a multitude of novel clearing methodologies including CUBIC (clear, unobstructed brain imaging cocktails and computational analysis), SWITCH (system-wide control of interaction time and kinetics of chemicals), MAP (magnified analysis of the proteome), and PACT (passive clarity technique), have been established to further expand the existing toolkit for the microscopic analysis of biological tissues. The present study aims to improve upon and optimize the original PACT procedure for an array of intact rodent tissues, including the whole central nervous system (CNS), kidneys, spleen, and whole mouse embryos. Termed psPACT (process-separate PACT) and mPACT (modified PACT), these novel techniques provide highly efficacious means of mapping cell circuitry and visualizing subcellular structures in intact normal and pathological tissues. In the following protocol, we provide a detailed, step-by-step outline on how to achieve maximal tissue clearance with minimal invasion of their structural integrity via psPACT and mPACT.

A spatiotemporal atlas of MR intensity, tissue probability and shape of the fetal brain with application to segmentation

PubMed Central

Habas, Piotr A.; Kim, Kio; Corbett-Detig, James M.; Rousseau, Francois; Glenn, Orit A.; Barkovich, A. James; Studholme, Colin

2010-01-01

Modeling and analysis of MR images of the developing human brain is a challenge due to rapid changes in brain morphology and morphometry. We present an approach to the construction of a spatiotemporal atlas of the fetal brain with temporal models of MR intensity, tissue probability and shape changes. This spatiotemporal model is created from a set of reconstructed MR images of fetal subjects with different gestational ages. Groupwise registration of manual segmentations and voxelwise nonlinear modeling allow us to capture the appearance, disappearance and spatial variation of brain structures over time. Applying this model to atlas-based segmentation, we generate age-specific MR templates and tissue probability maps and use them to initialize automatic tissue delineation in new MR images. The choice of model parameters and the final performance are evaluated using clinical MR scans of young fetuses with gestational ages ranging from 20.57 to 24.71 weeks. Experimental results indicate that quadratic temporal models can correctly capture growth-related changes in the fetal brain anatomy and provide improvement in accuracy of atlas-based tissue segmentation. PMID:20600970

Chemical Probes for Visualizing Intact Animal and Human Brain Tissue.

PubMed

Lai, Hei Ming; Ng, Wai-Lung; Gentleman, Steve M; Wu, Wutian

2017-06-22

Newly developed tissue clearing techniques can be used to render intact tissues transparent. When combined with fluorescent labeling technologies and optical sectioning microscopy, this allows visualization of fine structure in three dimensions. Gene-transfection techniques have proved very useful in visualizing cellular structures in animal models, but they are not applicable to human brain tissue. Here, we discuss the characteristics of an ideal chemical fluorescent probe for use in brain and other cleared tissues, and offer a comprehensive overview of currently available chemical probes. We describe their working principles and compare their performance with the goal of simplifying probe selection for neuropathologists and stimulating probe development by chemists. We propose several approaches for the development of innovative chemical labeling methods which, when combined with tissue clearing, have the potential to revolutionize how we study the structure and function of the human brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Injectable, cellular-scale optoelectronics with applications for wireless optogenetics.

PubMed

Kim, Tae-il; McCall, Jordan G; Jung, Yei Hwan; Huang, Xian; Siuda, Edward R; Li, Yuhang; Song, Jizhou; Song, Young Min; Pao, Hsuan An; Kim, Rak-Hwan; Lu, Chaofeng; Lee, Sung Dan; Song, Il-Sun; Shin, Gunchul; Al-Hasani, Ream; Kim, Stanley; Tan, Meng Peun; Huang, Yonggang; Omenetto, Fiorenzo G; Rogers, John A; Bruchas, Michael R

2013-04-12

Successful integration of advanced semiconductor devices with biological systems will accelerate basic scientific discoveries and their translation into clinical technologies. In neuroscience generally, and in optogenetics in particular, the ability to insert light sources, detectors, sensors, and other components into precise locations of the deep brain yields versatile and important capabilities. Here, we introduce an injectable class of cellular-scale optoelectronics that offers such features, with examples of unmatched operational modes in optogenetics, including completely wireless and programmed complex behavioral control over freely moving animals. The ability of these ultrathin, mechanically compliant, biocompatible devices to afford minimally invasive operation in the soft tissues of the mammalian brain foreshadow applications in other organ systems, with potential for broad utility in biomedical science and engineering.

Graphene-Based Interfaces Do Not Alter Target Nerve Cells.

PubMed

Fabbro, Alessandra; Scaini, Denis; León, Verónica; Vázquez, Ester; Cellot, Giada; Privitera, Giulia; Lombardi, Lucia; Torrisi, Felice; Tomarchio, Flavia; Bonaccorso, Francesco; Bosi, Susanna; Ferrari, Andrea C; Ballerini, Laura; Prato, Maurizio

2016-01-26

Neural-interfaces rely on the ability of electrodes to transduce stimuli into electrical patterns delivered to the brain. In addition to sensitivity to the stimuli, stability in the operating conditions and efficient charge transfer to neurons, the electrodes should not alter the physiological properties of the target tissue. Graphene is emerging as a promising material for neuro-interfacing applications, given its outstanding physico-chemical properties. Here, we use graphene-based substrates (GBSs) to interface neuronal growth. We test our GBSs on brain cell cultures by measuring functional and synaptic integrity of the emerging neuronal networks. We show that GBSs are permissive interfaces, even when uncoated by cell adhesion layers, retaining unaltered neuronal signaling properties, thus being suitable for carbon-based neural prosthetic devices.

Two-photon microscope for multisite microphotolysis of caged neurotransmitters in acute brain slices

PubMed Central

Losavio, Bradley E.; Iyer, Vijay; Saggau, Peter

2009-01-01

We developed a two-photon microscope optimized for physiologically manipulating single neurons through their postsynaptic receptors. The optical layout fulfills the stringent design criteria required for high-speed, high-resolution imaging in scattering brain tissue with minimal photodamage. We detail the practical compensation of spectral and temporal dispersion inherent in fast laser beam scanning with acousto-optic deflectors, as well as a set of biological protocols for visualizing nearly diffraction-limited structures and delivering physiological synaptic stimuli. The microscope clearly resolves dendritic spines and evokes electrophysiological transients in single neurons that are similar to endogenous responses. This system enables the study of multisynaptic integration and will assist our understanding of single neuron function and dendritic computation. PMID:20059271

In vitro terahertz spectroscopy of gelatin-embedded human brain tumors: a pilot study

NASA Astrophysics Data System (ADS)

Chernomyrdin, N. V.; Gavdush, A. A.; Beshplav, S.-I. T.; Malakhov, K. M.; Kucheryavenko, A. S.; Katyba, G. M.; Dolganova, I. N.; Goryaynov, S. A.; Karasik, V. E.; Spektor, I. E.; Kurlov, V. N.; Yurchenko, S. O.; Komandin, G. A.; Potapov, A. A.; Tuchin, V. V.; Zaytsev, K. I.

2018-04-01

We have performed the in vitro terahertz (THz) spectroscopy of human brain tumors. In order to fix tissues for the THz measurements, we have applied the gelatin embedding. It allows for preserving tissues from hydration/dehydration and sustaining their THz response similar to that of the freshly-excised tissues for a long time after resection. We have assembled an experimental setup for the reflection-mode measurements of human brain tissues based on the THz pulsed spectrometer. We have used this setup to study in vitro the refractive index and the amplitude absorption coefficient of 2 samples of malignant glioma (grade IV), 1 sample of meningioma (grade I), and samples of intact tissues. We have observed significant differences between the THz responses of normal and pathological tissues of the brain. The results of this paper highlight the potential of the THz technology in the intraoperative neurodiagnosis of tumors relying on the endogenous labels of tumorous tissues.

Gene expression profiles help identify the tissue of origin for metastatic brain cancers.

PubMed

Wu, Alan H B; Drees, Julia C; Wang, Hangpin; VandenBerg, Scott R; Lal, Anita; Henner, William D; Pillai, Raji

2010-04-26

Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA) is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3%) cases. This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers.

Gene expression profiles help identify the Tissue of Origin for metastatic brain cancers

PubMed Central

2010-01-01

Background Metastatic brain cancers are the most common intracranial tumor and occur in about 15% of all cancer patients. In up to 10% of these patients, the primary tumor tissue remains unknown, even after a time consuming and costly workup. The Pathwork® Tissue of Origin Test (Pathwork Diagnostics, Redwood City, CA, USA) is a gene expression test to aid in the diagnosis of metastatic, poorly differentiated and undifferentiated tumors. It measures the expression pattern of 1,550 genes in these tumors and compares it to the expression pattern of a panel of 15 known tumor types. The purpose of this study was to evaluate the performance of the Tissue of Origin Test in the diagnosis of primary sites for metastatic brain cancer patients. Methods Fifteen fresh-frozen metastatic brain tumor specimens of known origins met specimen requirements. These specimens were entered into the study and processed using the Tissue of Origin Test. Results were compared to the known primary site and the agreement between the two results was assessed. Results Fourteen of the fifteen specimens produced microarray data files that passed all quality metrics. One originated from a tissue type that was off-panel. Among the remaining 13 cases, the Tissue of Origin Test accurately predicted the available diagnosis in 12/13 (92.3%) cases. Discussion This study demonstrates the accuracy of the Tissue of Origin Test when applied to predict the tissue of origin of metastatic brain tumors. This test could be a very useful tool for pathologists as they classify metastatic brain cancers. PMID:20420692

Effect of baculovirus P35 protein on apoptosis in brain tissue of rats with acute cerebral infarction.

PubMed

Ji, J F; Ma, X H

2015-08-10

We explored the effect of baculovirus P35 protein on apoptosis in the brain tissue of rats with acute cerebral infarction (ACI). A rat model of middle cerebral artery infarction was created. The rats were randomly divided into sham, model, and treatment groups. Baculovirus P35 protein was injected into the intracranial arteries of the treatment group rats. The rats in the model group were given an equal volume of phosphate-buffered saline. The rats were sacrificed after 72 h and the brain tissue was separated. The levels of caspase-3, Bcl-2, and Bax mRNA, the brain cell apoptosis index, and the infarct size were determined. After 72 h, the levels of caspase-3 and Bax mRNA in the model and treatment groups were significantly greater than in the sham group, and the levels of Bcl-2 mRNA were significantly smaller (P < 0.05). The levels of caspase-3 and Bax mRNA were significantly lower in the treatment group than in the model group, and the level of Bcl-2 mRNA was significantly greater (P < 0.05). Compared with the sham group, the brain tissue apoptosis index and the cerebral infarction area increased significantly in the model and treatment groups (P < 0.05). The brain tissue apoptosis index and cerebral infarction area in the treatment group were significantly lower than in the model group (P < 0.05). Baculovirus P35 protein can effectively inhibit brain cell apoptosis in rats with ACI. It delayed apoptosis and necrosis in subjects with ACI tissue and had a protective effect on brain tissue.

Quantitative assessment of brain tissue oxygenation in porcine models of cardiac arrest and cardiopulmonary resuscitation using hyperspectral near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Lotfabadi, Shahin S.; Toronov, Vladislav; Ramadeen, Andrew; Hu, Xudong; Kim, Siwook; Dorian, Paul; Hare, Gregory M. T.

2014-03-01

Near-infrared spectroscopy (NIRS) is a non-invasive tool to measure real-time tissue oxygenation in the brain. In an invasive animal experiment we were able to directly compare non-invasive NIRS measurements on the skull with invasive measurements directly on the brain dura matter. We used a broad-band, continuous-wave hyper-spectral approach to measure tissue oxygenation in the brain of pigs under the conditions of cardiac arrest, cardiopulmonary resuscitation (CPR), and defibrillation. An additional purpose of this research was to find a correlation between mortality due to cardiac arrest and inadequacy of the tissue perfusion during attempts at resuscitation. Using this technique we measured the changes in concentrations of oxy-hemoglobin [HbO2] and deoxy-hemoglobin [HHb] to quantify the tissue oxygenation in the brain. We also extracted cytochrome c oxidase changes Δ[Cyt-Ox] under the same conditions to determine increase or decrease in cerebral oxygen delivery. In this paper we proved that applying CPR, [HbO2] concentration and tissue oxygenation in the brain increase while [HHb] concentration decreases which was not possible using other measurement techniques. We also discovered a similar trend in changes of both [Cyt-Ox] concentration and tissue oxygen saturation (StO2). Both invasive and non-invasive measurements showed similar results.

Enhancing the discrimination accuracy between metastases, gliomas and meningiomas on brain MRI by volumetric textural features and ensemble pattern recognition methods.

PubMed

Georgiadis, Pantelis; Cavouras, Dionisis; Kalatzis, Ioannis; Glotsos, Dimitris; Athanasiadis, Emmanouil; Kostopoulos, Spiros; Sifaki, Koralia; Malamas, Menelaos; Nikiforidis, George; Solomou, Ekaterini

2009-01-01

Three-dimensional (3D) texture analysis of volumetric brain magnetic resonance (MR) images has been identified as an important indicator for discriminating among different brain pathologies. The purpose of this study was to evaluate the efficiency of 3D textural features using a pattern recognition system in the task of discriminating benign, malignant and metastatic brain tissues on T1 postcontrast MR imaging (MRI) series. The dataset consisted of 67 brain MRI series obtained from patients with verified and untreated intracranial tumors. The pattern recognition system was designed as an ensemble classification scheme employing a support vector machine classifier, specially modified in order to integrate the least squares features transformation logic in its kernel function. The latter, in conjunction with using 3D textural features, enabled boosting up the performance of the system in discriminating metastatic, malignant and benign brain tumors with 77.14%, 89.19% and 93.33% accuracy, respectively. The method was evaluated using an external cross-validation process; thus, results might be considered indicative of the generalization performance of the system to "unseen" cases. The proposed system might be used as an assisting tool for brain tumor characterization on volumetric MRI series.

Multimodality instrument for tissue characterization

NASA Technical Reports Server (NTRS)

Mah, Robert W. (Inventor); Andrews, Russell J. (Inventor)

2004-01-01

A system with multimodality instrument for tissue identification includes a computer-controlled motor driven heuristic probe with a multisensory tip. For neurosurgical applications, the instrument is mounted on a stereotactic frame for the probe to penetrate the brain in a precisely controlled fashion. The resistance of the brain tissue being penetrated is continually monitored by a miniaturized strain gauge attached to the probe tip. Other modality sensors may be mounted near the probe tip to provide real-time tissue characterizations and the ability to detect the proximity of blood vessels, thus eliminating errors normally associated with registration of pre-operative scans, tissue swelling, elastic tissue deformation, human judgement, etc., and rendering surgical procedures safer, more accurate, and efficient. A neural network program adaptively learns the information on resistance and other characteristic features of normal brain tissue during the surgery and provides near real-time modeling. A fuzzy logic interface to the neural network program incorporates expert medical knowledge in the learning process. Identification of abnormal brain tissue is determined by the detection of change and comparison with previously learned models of abnormal brain tissues. The operation of the instrument is controlled through a user friendly graphical interface. Patient data is presented in a 3D stereographics display. Acoustic feedback of selected information may optionally be provided. Upon detection of the close proximity to blood vessels or abnormal brain tissue, the computer-controlled motor immediately stops probe penetration. The use of this system will make surgical procedures safer, more accurate, and more efficient. Other applications of this system include the detection, prognosis and treatment of breast cancer, prostate cancer, spinal diseases, and use in general exploratory surgery.

Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication.

PubMed

Li, Faith C H; Yen, J C; Chan, Samuel H H; Chang, Alice Y W

2012-02-07

Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism. The distribution of METH in brain and heart on intravenous administration in male Sprague-Dawley rats, and the resultant changes in arterial pressure (AP), heart rate (HR) and indices for baroreflex-mediated sympathetic vasomotor tone and cardiac responses were evaluated, alongside survival rate and time. Intravenous administration of METH (12 or 24 mg/kg) resulted in a time-dependent and dose-dependent distribution of the psychostimulant in brain and heart. The distribution of METH to neural substrates associated with brain stem cardiovascular regulation was significantly larger than brain targets for its neurological and psychological effects; the concentration of METH in cardiac tissues was the lowest among all tissues studied. In animals that succumbed to METH, the baroreflex-mediated sympathetic vasomotor tone and cardiac response were defunct, concomitant with cessation of AP and HR. On the other hand, although depressed, those two indices in animals that survived were maintained, alongside sustainable AP and HR. Linear regression analysis further revealed that the degree of dampening of brain stem cardiovascular regulation was positively and significantly correlated with the concentration of METH in key neural substrate involved in this homeostatic mechanism. We conclude that on intravenous administration, METH exhibits a preferential distribution to brain stem nuclei that are associated with cardiovascular regulation. We further found that the concentration of METH in those brain stem sites dictates the extent that baroreflex-mediated sympathetic vasomotor tone and cardiac responses are compromised, which in turn determines survival or fatality because of cardiovascular collapse.

Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication

PubMed Central

2012-01-01

Background Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism. Methods The distribution of METH in brain and heart on intravenous administration in male Sprague-Dawley rats, and the resultant changes in arterial pressure (AP), heart rate (HR) and indices for baroreflex-mediated sympathetic vasomotor tone and cardiac responses were evaluated, alongside survival rate and time. Results Intravenous administration of METH (12 or 24 mg/kg) resulted in a time-dependent and dose-dependent distribution of the psychostimulant in brain and heart. The distribution of METH to neural substrates associated with brain stem cardiovascular regulation was significantly larger than brain targets for its neurological and psychological effects; the concentration of METH in cardiac tissues was the lowest among all tissues studied. In animals that succumbed to METH, the baroreflex-mediated sympathetic vasomotor tone and cardiac response were defunct, concomitant with cessation of AP and HR. On the other hand, although depressed, those two indices in animals that survived were maintained, alongside sustainable AP and HR. Linear regression analysis further revealed that the degree of dampening of brain stem cardiovascular regulation was positively and significantly correlated with the concentration of METH in key neural substrate involved in this homeostatic mechanism. Conclusions We conclude that on intravenous administration, METH exhibits a preferential distribution to brain stem nuclei that are associated with cardiovascular regulation. We further found that the concentration of METH in those brain stem sites dictates the extent that baroreflex-mediated sympathetic vasomotor tone and cardiac responses are compromised, which in turn determines survival or fatality because of cardiovascular collapse. PMID:22313577

Therapeutic Ultrasound Enhancement of Drug Delivery to Soft Tissues

NASA Astrophysics Data System (ADS)

Lewis, George; Wang, Peng; Lewis, George; Olbricht, William

2009-04-01

Effects of exposure to 1.58 MHz focused ultrasound on transport of Evans Blue Dye (EBD) in soft tissues are investigated when an external pressure gradient is applied to induce convective flow through the tissue. The magnitude of the external pressure gradient is chosen to simulate conditions in brain parenchyma during convection-enhanced drug delivery (CED) to the brain. EBD uptake and transport are measured in equine brain, avian muscle and agarose brain-mimicking phantoms. Results show that ultrasound enhances EBD uptake and transport, and the greatest enhancement occurs when the external pressure gradient is applied. The results suggest that exposure of the brain parenchyma to ultrasound could enhance penetration of material infused into the brain during CED therapy.

Biochemical Fractionation and Stable Isotope Dilution Liquid Chromatography-mass Spectrometry for Targeted and Microdomain-specific Protein Quantification in Human Postmortem Brain Tissue*

PubMed Central

MacDonald, Matthew L.; Ciccimaro, Eugene; Prakash, Amol; Banerjee, Anamika; Seeholzer, Steven H.; Blair, Ian A.; Hahn, Chang-Gyu

2012-01-01

Synaptic architecture and its adaptive changes require numerous molecular events that are both highly ordered and complex. A majority of neuropsychiatric illnesses are complex trait disorders, in which multiple etiologic factors converge at the synapse via many signaling pathways. Investigating the protein composition of synaptic microdomains from human patient brain tissues will yield valuable insights into the interactions of risk genes in many disorders. These types of studies in postmortem tissues have been limited by the lack of proper study paradigms. Thus, it is necessary not only to develop strategies to quantify protein and post-translational modifications at the synapse, but also to rigorously validate them for use in postmortem human brain tissues. In this study we describe the development of a liquid chromatography-selected reaction monitoring method, using a stable isotope-labeled neuronal proteome standard prepared from the brain tissue of a stable isotope-labeled mouse, for the multiplexed quantification of target synaptic proteins in mammalian samples. Additionally, we report the use of this method to validate a biochemical approach for the preparation of synaptic microdomain enrichments from human postmortem prefrontal cortex. Our data demonstrate that a targeted mass spectrometry approach with a true neuronal proteome standard facilitates accurate and precise quantification of over 100 synaptic proteins in mammalian samples, with the potential to quantify over 1000 proteins. Using this method, we found that protein enrichments in subcellular fractions prepared from human postmortem brain tissue were strikingly similar to those prepared from fresh mouse brain tissue. These findings demonstrate that biochemical fractionation methods paired with targeted proteomic strategies can be used in human brain tissues, with important implications for the study of neuropsychiatric disease. PMID:22942359

Cranial irradiation increases tumor growth in experimental breast cancer brain metastasis.

PubMed

Hamilton, Amanda M; Wong, Suzanne M; Wong, Eugene; Foster, Paula J

2018-05-01

Whole-brain radiotherapy is the standard of care for patients with breast cancer with multiple brain metastases and, although this treatment has been essential in the management of existing brain tumors, there are many known negative consequences associated with the irradiation of normal brain tissue. In our study, we used in vivo magnetic resonance imaging analysis to investigate the influence of radiotherapy-induced damage of healthy brain on the arrest and growth of metastatic breast cancer cells in a mouse model of breast cancer brain metastasis. We observed that irradiated, but otherwise healthy, neural tissue had an increased propensity to support metastatic growth compared with never-irradiated controls. The elucidation of the impact of irradiation on normal neural tissue could have implications in clinical patient management, particularly in patients with residual systemic disease or with residual radio-resistant brain cancer. Copyright © 2018 John Wiley & Sons, Ltd.

Effects of acupuncture on tissue oxygenation of the rat brain.

PubMed

Chen, G S; Erdmann, W

1978-04-01

Acupuncture has been claimed to be effective in restoring consciousness in some comatose patients. Possible mechanisms to explain alleged acupuncture-induced arousal may include vasodilatory effects caused by smypathetic stimulation which leads to an augmentation of cerebral microcirculation and thereby improves oxygen supply to the brain tissue. Experiments were performed in ten albino rats (Wistar) employing PO2 microelectrodes which were inserted into the cortex through small burholes. Brain tissue PO2 was continuously recorded before, during, and after acupuncture. Stimulation of certain acupuncture points (Go-26) resulted in immediate increase of PO2 in the frontal cortex of the rat brain. This effect was reproducible and was comparable to that obtained with increase of inspiratory CO2 known to induce arterial vasodilatation and thus capillary perfusion pressure. The effect was more significant as compared to tissue PO2 increases obtained after increase in inspiratory oxygen concentration from 21% to 100%. It appears that acupuncture causes increased brain tissue perfusion which may be, at least in part, responsible for arousal of unconscious patients.

Metals in tissues of migrant semipalmated sandpipers (Calidris pusilla) from Delaware Bay, New Jersey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burger, Joanna, E-mail: burger@biology.rutgers.edu; Environmental and Occupational Health Sciences Institute; Gochfeld, Michael

2014-08-15

There is an abundance of field data on levels of metals for feathers in a variety of birds, but relatively few data for tissues, especially for migrant species from one location. In this paper we examine the levels of arsenic, cadmium, chromium, lead, manganese, mercury and selenium in muscle, liver, brain, fat and breast feathers from migrant semipalmated sandpipers (Calidris pusilla) collected from Delaware Bay, New Jersey. Our primary objectives were to (1) examine variation as a function of tissue, (2) determine the relationship of metal levels among tissues, and (3) determine the selenium:mercury molar ratio in different tissues sincemore » selenium is thought to protect against mercury toxicity. We were also interested in whether the large physiological changes that occur while shorebirds are on Delaware Bay (e.g. large weight gains in 2–3 weeks) affected metal levels, especially in the brain. There were significant differences among tissues for all metals. The brain had the lowest levels of arsenic and cadmium, and was tied for the lowest levels of all other metals except lead and selenium. Correlations among metals in tissues were varied, with mercury levels being positively correlated for muscle and brain, and for liver and breast feathers. Weights vary among individuals at the Delaware Bay stopover, as they arrive light, and gain weight prior to migration north. Bird weight and levels of arsenic, cadmium, and selenium in the brain were negatively correlated, while they were positively correlated for lead. There was no positive correlation for mercury in the brain as a function of body weight. The selenium:mercury molar ratio varied significantly among tissues, with brain (ratio of 141) and fat having the highest ratios, and liver and breast feathers having the lowest. In all cases, the ratio was above 21, suggesting the potential for amelioration of mercury toxicity. - Highlights: • Metal levels were examined for migrant semipalmated sandpipers. • There were differences in metal levels among internal tissues. • Brain had the lowest levels of arsenic and cadmium. • Bird weight and arsenic, cadmium, and selenium levels in brain were negatively correlated. • Selenium:mercury molar ratio varied among tissues (21–141, suggesting protection)« less

Compression stiffening of brain and its effect on mechanosensing by glioma cells

NASA Astrophysics Data System (ADS)

Pogoda, Katarzyna; Chin, LiKang; Georges, Penelope C.; Byfield, FitzRoy J.; Bucki, Robert; Kim, Richard; Weaver, Michael; Wells, Rebecca G.; Marcinkiewicz, Cezary; Janmey, Paul A.

2014-07-01

Many cell types, including neurons, astrocytes and other cells of the central nervous system, respond to changes in the extracellular matrix or substrate viscoelasticity, and increased tissue stiffness is a hallmark of several disease states, including fibrosis and some types of cancers. Whether the malignant tissue in brain, an organ that lacks the protein-based filamentous extracellular matrix of other organs, exhibits the same macroscopic stiffening characteristic of breast, colon, pancreatic and other tumors is not known. In this study we show that glioma cells, like normal astrocytes, respond strongly in vitro to substrate stiffness in the range of 100 to 2000 Pa, but that macroscopic (mm to cm) tissue samples isolated from human glioma tumors have elastic moduli in the order of 200 Pa that are indistinguishable from those of normal brain. However, both normal brain and glioma tissues increase their shear elastic moduli under modest uniaxial compression, and glioma tissue stiffens more strongly under compression than normal brain. These findings suggest that local tissue stiffness has the potential to alter glial cell function, and that stiffness changes in brain tumors might arise not from increased deposition or crosslinking of the collagen-rich extracellular matrix, but from pressure gradients that form within the tumors in vivo.

Mary Jane Hogue (1883-1962): A pioneer in human brain tissue culture.

PubMed

Zottoli, Steven J; Seyfarth, Ernst-August

2018-05-16

The ability to maintain human brain explants in tissue culture was a critical step in the use of these cells for the study of central nervous system disorders. Ross G. Harrison (1870-1959) was the first to successfully maintain frog medullary tissue in culture in 1907, but it took another 38 years before successful culture of human brain tissue was accomplished. One of the pioneers in this achievement was Mary Jane Hogue (1883-1962). Hogue was born into a Quaker family in 1883 in West Chester, Pennsylvania, and received her undergraduate degree from Goucher College in Baltimore, Maryland. Research with the developmental biologist Theodor Boveri (1862-1915) in Würzburg, Germany, resulted in her Ph.D. (1909). Hogue transitioned from studying protozoa to the culture of human brain tissue in the 1940s and 1950s, when she was one of the first to culture cells from human fetal, infant, and adult brain explants. We review Hogue's pioneering contributions to the study of human brain cells in culture, her putative identification of progenitor neuroblast and/or glioblast cells, and her use of the cultures to study the cytopathogenic effects of poliovirus. We also put Hogue's work in perspective by discussing how other women pioneers in tissue culture influenced Hogue and her research.

Mimicking brain tissue binding in an in vitro model of the blood-brain barrier illustrates differences between in vitro and in vivo methods for assessing the rate of brain penetration.

PubMed

Heymans, Marjolein; Sevin, Emmanuel; Gosselet, Fabien; Lundquist, Stefan; Culot, Maxime

2018-06-01

Assessing the rate of drug delivery to the central nervous system (CNS) in vitro has been used for decades to predict whether CNS drug candidates are likely to attain their pharmacological targets, located within the brain parenchyma, at an effective dose. The predictive value of in vitro blood-brain barrier (BBB) models is therefore frequently assessed by comparing in vitro BBB permeability, usually quoted as the endothelial permeability coefficient (P e ) or apparent permeability (P app ), to their rate of BBB permeation measured in vivo, the latter being commonly assessed in rodents. In collaboration with AstraZeneca (DMPK department, Södertälje, Sweden), the in vitro BBB permeability (P app and P e ) of 27 marketed CNS drugs has been determined using a bovine in vitro BBB model and compared to their in vivo permeability (P vivo ), obtained by rat in-situ brain perfusion. The latter was taken from published data from Summerfield et al. (2007). This comparison confirmed previous reports, showing a strong in vitro/in vivo correlation for hydrophilic compounds, characterized by low brain tissue binding and a weak correlation for lipophilic compounds, characterized by high brain tissue binding. This observation can be explained by the influence of brain tissue binding on the uptake of drugs into the CNS in vivo and the absence of possible brain tissue binding in vitro. The use of glial cells (GC) in the in vitro BBB model to mimic brain tissue binding and the introduction of a new calculation method for in vitro BBB permeability (P vitro ) resulted in a strong correlation between the in vitro and in vivo rate of BBB permeation for the whole set of compounds. These findings might facilitate further in vitro to in vivo extrapolation for CNS drug candidates. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Development and Validation of a Method for Alcohol Analysis in Brain Tissue by Headspace Gas Chromatography with Flame Ionization Detector

PubMed Central

Chun, Hao-Jung; Poklis, Justin L.; Poklis, Alphonse; Wolf, Carl E.

2016-01-01

Ethanol is the most widely used and abused drug. While blood is the preferred specimen for analysis, tissue specimens such as brain serve as alternative specimens for alcohol analysis in post-mortem cases where blood is unavailable or contaminated. A method was developed using headspace gas chromatography with flame ionization detection (HS-GC-FID) for the detection and quantification of ethanol, acetone, isopropanol, methanol and n-propanol in brain tissue specimens. Unfixed volatile-free brain tissue specimens were obtained from the Department of Pathology at Virginia Commonwealth University. Calibrators and controls were prepared from 4-fold diluted homogenates of these brain tissue specimens, and were analyzed using t-butanol as the internal standard. The chromatographic separation was performed with a Restek BAC2 column. A linear calibration was generated for all analytes (mean r2 > 0.9992) with the limits of detection and quantification of 100–110 mg/kg. Matrix effect from the brain tissue was determined by comparing the slopes of matrix prepared calibration curves with those of aqueous calibration curves; no significant differences were observed for ethanol, acetone, isopropanol, methanol and n-propanol. The bias and the CVs for all volatile controls were ≤10%. The method was also evaluated for carryover, selectivity, interferences, bench-top stability and freeze-thaw stability. The HS-GC-FID method was determined to be reliable and robust for the analysis of ethanol, acetone, isopropanol, methanol and n-propanol concentrations in brain tissue, effectively expanding the specimen options for post-mortem alcohol analysis. PMID:27488829

A Novel Biopsy Method for Isolating Neural Stem Cells from the Subventricular Zone of the Adult Rat Brain for Autologous Transplantation in CNS Injuries.

PubMed

Aligholi, Hadi; Hassanzadeh, Gholamreza; Gorji, Ali; Azari, Hassan

2016-01-01

Despite all attempts the problem of regeneration in damaged central nervous system (CNS) has remained challenging due to its cellular complexity and highly organized and sophisticated connections. In this regard, stem cell therapy might serve as a viable therapeutic approach aiming either to support the damaged tissue and hence to reduce the subsequent neurological dysfunctions and impairments or to replace the lost cells and re-establish damaged circuitries. Adult neural stem/progenitor cells (NS/PCs) are one of the outstanding cell sources that can be isolated from the subventricular zone (SVZ) of the lateral ventricles. These cells can differentiate into neurons, astrocytes, and oligodendrocytes. Implanting autologous NS/PCs will greatly benefit the patients by avoiding immune rejection after implantation, better survival, and integration with the host tissue. Developing safe and efficient methods in small animal models will provide us with the opportunity to optimize procedures required to achieve successful human autologous NS/PC transplantation in near future. In this chapter, a highly controlled and safe biopsy method for harvesting stem cell containing tissue from the SVZ of adult rat brain is introduced. Then, isolation and expansion of NS/PCs from harvested specimen as well as the techniques to verify proliferation and differentiation capacity of the resulting NS/PCs are discussed. Finally, a method for assessing the biopsy lesion volume in the brain is described. This safe biopsy method in rat provides a unique tool to study autologous NS/PC transplantation in different CNS injury models.

S-nitrosoglutathione prevents blood-brain barrier disruption associated with increased matrix metalloproteinase-9 activity in experimental diabetes.

PubMed

Aggarwal, Aanchal; Khera, Alka; Singh, Inderjit; Sandhir, Rajat

2015-03-01

Hyperglycemia is known to induce microvascular complications, thereby altering blood-brain barrier (BBB) permeability. This study investigated the role of matrix metalloproteinases (MMPs) and their endogenous inhibitors in increased BBB permeability and evaluated the protective effect of S-nitrosoglutathione (GSNO) in diabetes. Diabetes was induced in mice by intraperitoneal injection of streptozotocin (40 mg/kg body weight) for 5 days and GSNO was administered orally (100 μg/kg body weight) daily for 8 weeks after the induction of diabetes. A significant decline in cognitive functions was observed in diabetic mice assessed by Morris water maze test. Increased permeability to different molecular size tracers accompanied by edema and ion imbalance was observed in cortex and hippocampus of diabetic mice. Furthermore, activity of both pro and active MMP-9 was found to be significantly elevated in diabetic animals. Increased in situ gelatinase activity was observed in tissue sections and isolated microvessels from diabetic mice brain. The increase in activity of MMP-9 was attributed to increased mRNA and protein expression in diabetic mice. In addition, a significant decrease in mRNA and protein expression of tissue inhibitor of matrix metalloproteinase-1 was also observed in diabetic animals. However, GSNO supplementation to diabetic animals was able to abridge MMP-9 activation as well as tissue inhibitor of matrix metalloproteinase-1 levels, restoring BBB integrity and also improving learning and memory. Our findings clearly suggest that GSNO could prevent hyperglycemia-induced disruption of BBB by suppressing MMP-9 activity. © 2014 International Society for Neurochemistry.

Near-infrared diffuse reflectance imaging of infarct core and peri-infarct depolarization in a rat middle cerebral artery occlusion model

NASA Astrophysics Data System (ADS)

Kawauchi, Satoko; Nishidate, Izumi; Nawashiro, Hiroshi; Sato, Shunichi

2014-03-01

To understand the pathophysiology of ischemic stroke, in vivo imaging of the brain tissue viability and related spreading depolarization is crucial. In the infarct core, impairment of energy metabolism causes anoxic depolarization (AD), which considerably increases energy consumption, accelerating irreversible neuronal damage. In the peri-infarct penumbra region, where tissue is still reversible despite limited blood flow, peri-infarct depolarization (PID) occurs, exacerbating energy deficit and hence expanding the infarct area. We previously showed that light-scattering signal, which is sensitive to cellular/subcellular structural integrity, was correlated with AD and brain tissue viability in a rat hypoxia-reoxygenation model. In the present study, we performed transcranial NIR diffuse reflectance imaging of the rat brain during middle cerebral artery (MCA) occlusion and examined whether the infarct core and PIDs can be detected. Immediately after occluding the left MCA, light scattering started to increase focally in the occlusion site and a bright region was generated near the occlusion site and spread over the left entire cortex, which was followed by a dark region, showing the occurrence of PID. The PID was generated repetitively and the number of times of occurrence in a rat ranged from four to ten within 1 hour after occlusion (n=4). The scattering increase in the occlusion site was irreversible and the area with increased scattering expanded with increasing the number of PIDs, indicating an expansion of the infarct core. These results suggest the usefulness of NIR diffuse reflectance signal to visualize spatiotemporal changes in the infarct area and PIDs.

Characterizing genes with distinct methylation patterns in the context of protein-protein interaction network: application to human brain tissues.

PubMed

Li, Yongsheng; Xu, Juan; Chen, Hong; Zhao, Zheng; Li, Shengli; Bai, Jing; Wu, Aiwei; Jiang, Chunjie; Wang, Yuan; Su, Bin; Li, Xia

2013-01-01

DNA methylation is an essential epigenetic mechanism involved in transcriptional control. However, how genes with different methylation patterns are assembled in the protein-protein interaction network (PPIN) remains a mystery. In the present study, we systematically dissected the characterization of genes with different methylation patterns in the PPIN. A negative association was detected between the methylation levels in the brain tissues and topological centralities. By focusing on two classes of genes with considerably different methylation levels in the brain tissues, namely the low methylated genes (LMGs) and high methylated genes (HMGs), we found that their organizing principles in the PPIN are distinct. The LMGs tend to be the center of the PPIN, and attacking them causes a more deleterious effect on the network integrity. Furthermore, the LMGs express their functions in a modular pattern and substantial differences in functions are observed between the two types of genes. The LMGs are enriched in the basic biological functions, such as binding activity and regulation of transcription. More importantly, cancer genes, especially recessive cancer genes, essential genes, and aging-related genes were all found more often in the LMGs. Additionally, our analysis presented that the intra-classes communications are enhanced, but inter-classes communications are repressed. Finally, a functional complementation was revealed between methylation and miRNA regulation in the human genome. We have elucidated the assembling principles of genes with different methylation levels in the context of the PPIN, providing key insights into the complex epigenetic regulation mechanisms.

Characterizing Genes with Distinct Methylation Patterns in the Context of Protein-Protein Interaction Network: Application to Human Brain Tissues

PubMed Central

Zhao, Zheng; Li, Shengli; Bai, Jing; Wu, Aiwei; Jiang, Chunjie; Wang, Yuan; Su, Bin; Li, Xia

2013-01-01

Background DNA methylation is an essential epigenetic mechanism involved in transcriptional control. However, how genes with different methylation patterns are assembled in the protein-protein interaction network (PPIN) remains a mystery. Results In the present study, we systematically dissected the characterization of genes with different methylation patterns in the PPIN. A negative association was detected between the methylation levels in the brain tissues and topological centralities. By focusing on two classes of genes with considerably different methylation levels in the brain tissues, namely the low methylated genes (LMGs) and high methylated genes (HMGs), we found that their organizing principles in the PPIN are distinct. The LMGs tend to be the center of the PPIN, and attacking them causes a more deleterious effect on the network integrity. Furthermore, the LMGs express their functions in a modular pattern and substantial differences in functions are observed between the two types of genes. The LMGs are enriched in the basic biological functions, such as binding activity and regulation of transcription. More importantly, cancer genes, especially recessive cancer genes, essential genes, and aging-related genes were all found more often in the LMGs. Additionally, our analysis presented that the intra-classes communications are enhanced, but inter-classes communications are repressed. Finally, a functional complementation was revealed between methylation and miRNA regulation in the human genome. Conclusions We have elucidated the assembling principles of genes with different methylation levels in the context of the PPIN, providing key insights into the complex epigenetic regulation mechanisms. PMID:23776563

Hyper- and viscoelastic modeling of needle and brain tissue interaction.

PubMed

Lehocky, Craig A; Yixing Shi; Riviere, Cameron N

2014-01-01

Deep needle insertion into brain is important for both diagnostic and therapeutic clinical interventions. We have developed an automated system for robotically steering flexible needles within the brain to improve targeting accuracy. In this work, we have developed a finite element needle-tissue interaction model that allows for the investigation of safe parameters for needle steering. The tissue model implemented contains both hyperelastic and viscoelastic properties to simulate the instantaneous and time-dependent responses of brain tissue. Several needle models were developed with varying parameters to study the effects of the parameters on tissue stress, strain and strain rate during needle insertion and rotation. The parameters varied include needle radius, bevel angle, bevel tip fillet radius, insertion speed, and rotation speed. The results will guide the design of safe needle tips and control systems for intracerebral needle steering.

The effect of nimodipine on cerebral oxygenation in patients with poor-grade subarachnoid hemorrhage.

PubMed

Stiefel, Michael F; Heuer, Gregory G; Abrahams, John M; Bloom, Stephanie; Smith, Michelle J; Maloney-Wilensky, Eileen; Grady, M Sean; LeRoux, Peter D

2004-10-01

Nimodipine has been shown to improve neurological outcome after subarachnoid hemorrhage (SAH); the mechanism of this improvement, however, is uncertain. In addition, adverse systemic effects such as hypotension have been described. The authors investigated the effect of nimodipine on brain tissue PO2. Patients in whom Hunt and Hess Grade IV or V SAH had occurred who underwent aneurysm occlusion and had stable blood pressure were prospectively evaluated using continuous brain tissue PO2 monitoring. Nimodipine (60 mg) was delivered through a nasogastric or Dobhoff tube every 4 hours. Data were obtained from 11 patients and measurements of brain tissue PO2, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were recorded every 15 minutes. Nimodipine resulted in a significant reduction in brain tissue PO2 in seven (64%) of 11 patients. The baseline PO2 before nimodipine administration was 38.4+/-10.9 mm Hg. The baseline MABP and CPP were 90+/-20 and 84+/-19 mm Hg, respectively. The greatest reduction in brain tissue PO2 occurred 15 minutes after administration, when the mean pressure was 26.9+/-7.7 mm Hg (p < 0.05). The PO2 remained suppressed at 30 minutes (27.5+/-7.7 mm Hg [p < 0.05]) and at 60 minutes (29.7+/-11.1 mm Hg [p < 0.05]) after nimodipine administration but returned to baseline levels 2 hours later. In the seven patients in whom brain tissue PO2 decreased, other physiological variables such as arterial saturation, end-tidal CO2, heart rate, MABP, ICP, and CPP did not demonstrate any association with the nimodipine-induced reduction in PO2. In four patients PO2 remained stable and none of these patients had a significant increase in brain tissue PO2. Although nimodipine use is associated with improved outcome following SAH, in some patients it can temporarily reduce brain tissue PO2.

Advantages of analyzing postmortem brain samples in routine forensic drug screening-Case series of three non-natural deaths tested positive for lysergic acid diethylamide (LSD).

PubMed

Mardal, Marie; Johansen, Sys Stybe; Thomsen, Ragnar; Linnet, Kristian

2017-09-01

Three case reports are presented, including autopsy findings and toxicological screening results, which were tested positive for the potent hallucinogenic drug lysergic acid diethylamide (LSD). LSD and its main metabolites were quantified in brain tissue and femoral blood, and furthermore hematoma and urine when available. LSD, its main metabolite 2-oxo-3-hydroxy-LSD (oxo-HO-LSD), and iso-LSD were quantified in biological samples according to a previously published procedure involving liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). LSD was measured in the brain tissue of all presented cases at a concentration level from 0.34-10.8μg/kg. The concentration level in the target organ was higher than in peripheral blood. Additional psychoactive compounds were quantified in blood and brain tissue, though all below toxic concentration levels. The cause of death in case 1 was collision-induced brain injury, while it was drowning in case 2 and 3 and thus not drug intoxication. However, the toxicological findings could help explain the decedent's inability to cope with brain injury or drowning incidents. The presented findings could help establish reference concentrations in brain samples and assist in interpretation of results from forensic drug screening in brain tissue. This is to the author's knowledge the first report of LSD, iso-LSD, and oxo-HO-LSD measured in brain tissue samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeting therapeutics across the blood brain barrier (BBB), prerequisite towards thrombolytic therapy for cerebrovascular disorders-an overview and advancements.

PubMed

Pulicherla, K K; Verma, Mahendra Kumar

2015-04-01

Cerebral tissues possess highly selective and dynamic protection known as blood brain barrier (BBB) that regulates brain homeostasis and provides protection against invading pathogens and various chemicals including drug molecules. Such natural protection strictly monitors entry of drug molecules often required for the management of several diseases and disorders including cerebral vascular and neurological disorders. However, in recent times, the ischemic cerebrovascular disease and clinical manifestation of acute arterial thrombosis are the most common causes of mortality and morbidity worldwide. The management of cerebral Ischemia requires immediate infusion of external thrombolytic into systemic circulation and must cross the blood brain barrier. The major challenge with available thrombolytic is their poor affinity towards the blood brain barrier and cerebral tissue subsequently. In the clinical practice, a high dose of thrombolytic often prescribed to deliver drugs across the blood brain barrier which results in drug dependent toxicity leading to damage of neuronal tissues. In recent times, more emphasis was given to utilize blood brain barrier transport mechanism to deliver drugs in neuronal tissue. The blood brain barrier expresses a series of receptor on membrane became an ideal target for selective drug delivery. In this review, the author has given more emphasis molecular biology of receptor on blood brain barrier and their potential as a carrier for drug molecules to cerebral tissues. Further, the use of nanoscale design and real-time monitoring for developed therapeutic to encounter drug dependent toxicity has been reviewed in this study.

Better diet quality relates to larger brain tissue volumes: The Rotterdam Study.

PubMed

Croll, Pauline H; Voortman, Trudy; Ikram, M Arfan; Franco, Oscar H; Schoufour, Josje D; Bos, Daniel; Vernooij, Meike W

2018-05-16

To investigate the relation of diet quality with structural brain tissue volumes and focal vascular lesions in a dementia-free population. From the population-based Rotterdam Study, 4,447 participants underwent dietary assessment and brain MRI scanning between 2005 and 2015. We excluded participants with an implausible energy intake, prevalent dementia, or cortical infarcts, leaving 4,213 participants for the current analysis. A diet quality score (0-14) was calculated reflecting adherence to Dutch dietary guidelines. Brain MRI was performed to obtain information on brain tissue volumes, white matter lesion volume, lacunes, and cerebral microbleeds. The associations of diet quality score and separate food groups with brain structures were assessed using multivariable linear and logistic regression. We found that better diet quality related to larger brain volume, gray matter volume, white matter volume, and hippocampal volume. Diet quality was not associated with white matter lesion volume, lacunes, or microbleeds. High intake of vegetables, fruit, whole grains, nuts, dairy, and fish and low intake of sugar-containing beverages were associated with larger brain volumes. A better diet quality is associated with larger brain tissue volumes. These results suggest that the effect of nutrition on neurodegeneration may act via brain structure. More research, in particular longitudinal research, is needed to unravel direct vs indirect effects between diet quality and brain health. © 2018 American Academy of Neurology.

Clinical imaging in regenerative medicine

PubMed Central

Naumova, Anna V; Modo, Michel; Moore, Anna; Murry, Charles E; Frank, Joseph A

2014-01-01

In regenerative medicine, clinical imaging is indispensable for characterizing damaged tissue and for measuring the safety and efficacy of therapy. However, the ability to track the fate and function of transplanted cells with current technologies is limited. Exogenous contrast labels such as nanoparticles give a strong signal in the short term but are unreliable long term. Genetically encoded labels are good both short- and long-term in animals, but in the human setting they raise regulatory issues related to the safety of genomic integration and potential immunogenicity of reporter proteins. Imaging studies in brain, heart and islets share a common set of challenges, including developing novel labeling approaches to improve detection thresholds and early delineation of toxicity and function. Key areas for future research include addressing safety concerns associated with genetic labels and developing methods to follow cell survival, differentiation and integration with host tissue. Imaging may bridge the gap between cell therapies and health outcomes by elucidating mechanisms of action through longitudinal monitoring. PMID:25093889

Permeabilization of brain tissue in situ enables multiregion analysis of mitochondrial function in a single mouse brain.

PubMed

Herbst, Eric A F; Holloway, Graham P

2015-02-15

Mitochondrial function in the brain is traditionally assessed through analysing respiration in isolated mitochondria, a technique that possesses significant tissue and time requirements while also disrupting the cooperative mitochondrial reticulum. We permeabilized brain tissue in situ to permit analysis of mitochondrial respiration with the native mitochondrial morphology intact, removing the need for isolation time and minimizing tissue requirements to ∼2 mg wet weight. The permeabilized brain technique was validated against the traditional method of isolated mitochondria and was then further applied to assess regional variation in the mouse brain with ischaemia-reperfusion injuries. A transgenic mouse model overexpressing catalase within mitochondria was applied to show the contribution of mitochondrial reactive oxygen species to ischaemia-reperfusion injuries in different brain regions. This technique enhances the accessibility of addressing physiological questions in small brain regions and in applying transgenic mouse models to assess mechanisms regulating mitochondrial function in health and disease. Mitochondria function as the core energy providers in the brain and symptoms of neurodegenerative diseases are often attributed to their dysregulation. Assessing mitochondrial function is classically performed in isolated mitochondria; however, this process requires significant isolation time, demand for abundant tissue and disruption of the cooperative mitochondrial reticulum, all of which reduce reliability when attempting to assess in vivo mitochondrial bioenergetics. Here we introduce a method that advances the assessment of mitochondrial respiration in the brain by permeabilizing existing brain tissue to grant direct access to the mitochondrial reticulum in situ. The permeabilized brain preparation allows for instant analysis of mitochondrial function with unaltered mitochondrial morphology using significantly small sample sizes (∼2 mg), which permits the analysis of mitochondrial function in multiple subregions within a single mouse brain. Here this technique was applied to assess regional variation in brain mitochondrial function with acute ischaemia-reperfusion injuries and to determine the role of reactive oxygen species in exacerbating dysfunction through the application of a transgenic mouse model overexpressing catalase within mitochondria. Through creating accessibility to small regions for the investigation of mitochondrial function, the permeabilized brain preparation enhances the capacity for examining regional differences in mitochondrial regulation within the brain, as the majority of genetic models used for unique approaches exist in the mouse model. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Drugs in the brain--cellular imaging with receptor microscopic autoradiography.

PubMed

Stumpf, Walter E

2012-03-01

For cell and tissue localization of drugs, receptor microscopic autoradiography is reviewed, including its development history, multiple testing, extensive applications and significant discoveries. This sensitive high-resolution imaging method is based on the use of radiolabeled compounds (esp. tagged with (3)H or (125)I), preservation through freezing of in vivo localization of tissue constituents, cutting thin frozen sections, and close contact with the recording nuclear emulsion. After extensive testing of the utility of this method, the distribution of radiolabeled compounds has been identified and characterized for estradiol, progestagens, adrenal steroids, thyroid hormone, ecdysteroids, vitamin D, retinoic acid, metabolic indicators glucose and 2-deoxyglucose, as well as extracellular space indicators. Target cells and associated tissues have been characterized with special stains, fluorescing compounds, or combined autoradiography-immunocytochemistry with antibodies to dopamine-beta-hydroxylase, GABA, enkephalin, specific receptor proteins, or other cellular products. Blood-brain barrier and brain entries via capillary endothelium, ependyma, or circumventricular recess organs have been visualized for (3)H-dexamethasone, (210)Pb lead, and (3)H-1,25(OH)(2) vitamin D(3). With this histopharmacologic approach, cellular details and tissue integrative overviews can be assessed in the same preparation. As a result, information has been gained that would have been difficult or impossible otherwise. Maps of brain drug distribution have been developed and relevant target circuits have been recognized. Examples include the stria terminalis that links septal-amygdaloid-thalamic-hypothalamic structures and telencephalic limbic system components which extend as the periventricular autonomic-neuroendocrine ABC (Allocortex-Brainstem-Circuitry) system into the mid- and hindbrain. Discoveries with radiolabeled substances challenged existing paradigms, engendering new concepts and providing seminal incentives for further research toward understanding drug actions. Most notable are discoveries made during the 1980s with vitamin D in the brain together with over 50 target tissues that challenged the century-old doctrine of vitamin D's main role as 'the calcitropic hormone', when the new data made it apparent that the main biological function of this multifunctional sunshine hormone rather is maintenance of life and adapting vital functions to the solar environment. In the brain, vitamin D, in close relation to sex and adrenal steroids, participates in the regulation of the secretion of neuro-endocrines, such as, serotonin, dopamine, nerve growth factor, acetyl choline, with importance in prophylaxis and therapy of neuro-psychiatric disorders. Histochemical imaging with high cellular-subcellular resolution is necessary for obtaining detailed information, as this review indicates. New spectrometric methods, like MALDI-MSI, are unlikely to furnish the same information as receptor microautoradiography does, but can provide important correlative molecular information. Copyright © 2011 Elsevier GmbH. All rights reserved.

Early intake of long-chain polyunsaturated fatty acids preserves brain structure and function in diet-induced obesity.

PubMed

Arnoldussen, Ilse A C; Zerbi, Valerio; Wiesmann, Maximilian; Noordman, Rikko H J; Bolijn, Simone; Mutsaers, Martina P C; Dederen, Pieter J W C; Kleemann, Robert; Kooistra, Teake; van Tol, Eric A F; Gross, Gabriele; Schoemaker, Marieke H; Heerschap, Arend; Wielinga, Peter Y; Kiliaan, Amanda J

2016-04-01

Worldwide, the incidence of obesity is increasing at an alarming rate, and the number of children with obesity is especially worrisome. These developments raise concerns about the physical, psychosocial and cognitive consequences of obesity. It was shown that early dietary intake of arachidonic acid (ARA) and docosahexaenoic acid (DHA) can reduce the detrimental effects of later obesogenic feeding on lipid metabolism and adipogenesis in an animal model of mild obesity. In the present study, the effects of early dietary ARA and DHA on cognition and brain structure were examined in mildly obesogenic ApoE*3Leiden mouse model. We used cognitive tests and neuroimaging during early and later life. During their early development after weaning (4-13weeks of age), mice were fed a chow diet or ARA and DHA diet for 8 weeks and then switched to a high-fat and high-carbohydrate (HFHC) diet for 12weeks (14-26weeks of age). An HFHC-diet led to increased energy storage in white adipose tissue, increased cholesterol levels, decreased triglycerides levels, increased cerebral blood flow and decreased functional connectivity between brain regions as well as cerebrovascular and gray matter integrity. ARA and DHA intake reduced the HFHC-diet-induced increase in body weight, attenuated plasma triglycerides levels and improved cerebrovasculature, gray matter integrity and functional connectivity in later life. In conclusion, an HFHC diet causes adverse structural brain and metabolic adaptations, most of which can be averted by dietary ARA and DHA intake early in life supporting metabolic flexibility and cerebral integrity later in life. Copyright © 2016 Elsevier Inc. All rights reserved.

Real-time simulation of contact and cutting of heterogeneous soft-tissues.

PubMed

Courtecuisse, Hadrien; Allard, Jérémie; Kerfriden, Pierre; Bordas, Stéphane P A; Cotin, Stéphane; Duriez, Christian

2014-02-01

This paper presents a numerical method for interactive (real-time) simulations, which considerably improves the accuracy of the response of heterogeneous soft-tissue models undergoing contact, cutting and other topological changes. We provide an integrated methodology able to deal both with the ill-conditioning issues associated with material heterogeneities, contact boundary conditions which are one of the main sources of inaccuracies, and cutting which is one of the most challenging issues in interactive simulations. Our approach is based on an implicit time integration of a non-linear finite element model. To enable real-time computations, we propose a new preconditioning technique, based on an asynchronous update at low frequency. The preconditioner is not only used to improve the computation of the deformation of the tissues, but also to simulate the contact response of homogeneous and heterogeneous bodies with the same accuracy. We also address the problem of cutting the heterogeneous structures and propose a method to update the preconditioner according to the topological modifications. Finally, we apply our approach to three challenging demonstrators: (i) a simulation of cataract surgery (ii) a simulation of laparoscopic hepatectomy (iii) a brain tumor surgery. Copyright © 2013 Elsevier B.V. All rights reserved.

Ischemic time impacts biological integrity of phospho-proteins in PI3K/Akt, Erk/MAPK, and p38 MAPK signaling networks.

PubMed

Holzer, Timothy R; Fulford, Angie D; Arkins, Austin M; Grondin, Janet M; Mundy, Christopher W; Nasir, Aejaz; Schade, Andrew E

2011-06-01

Post-translational modifications of proteins, such as phosphorylation, are labile events dynamically regulated by opposing kinase and phosphatase activities. Preanalytical factors, such as ischemic time before fixation, affect these activities and can have a significant impact on the ability to elucidate signaling pathways in tissue. Immunohistochemical analysis of phosphorylated proteins involved in PI3K/Akt, Erk/MAPK, and p38 MAPK signaling networks was performed in human cell line xenografts from lung, brain, ovary, and prostate tumors. In order to replicate real-world practices, the tissues were subjected to ischemic times of 0 (baseline), 1, 4, and 24 hours before fixation in formalin. Two key concepts emerge from this analysis: (1) the stability of different phospho-epitopes within a given tumor type is variable (e.g. phospho-PRAS40 is more labile than phospho-S6 ribosomal protein) and (2) the stability of a given phospho-epitope (e.g. phospho-MAPKAPK2) varies significantly across different tumor types. These results highlight the importance of proper tissue acquisition and rapid fixation to preserve the biological integrity of signal transduction pathways that may guide therapeutic decision making.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated networkmore » (p < 10{sup -53}) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease.« less

Improved two-photon imaging of living neurons in brain tissue through temporal gating

PubMed Central

Gautam, Vini; Drury, Jack; Choy, Julian M. C.; Stricker, Christian; Bachor, Hans-A.; Daria, Vincent R.

2015-01-01

We optimize two-photon imaging of living neurons in brain tissue by temporally gating an incident laser to reduce the photon flux while optimizing the maximum fluorescence signal from the acquired images. Temporal gating produces a bunch of ~10 femtosecond pulses and the fluorescence signal is improved by increasing the bunch-pulse energy. Gating is achieved using an acousto-optic modulator with a variable gating frequency determined as integral multiples of the imaging sampling frequency. We hypothesize that reducing the photon flux minimizes the photo-damage to the cells. Our results, however, show that despite producing a high fluorescence signal, cell viability is compromised when the gating and sampling frequencies are equal (or effectively one bunch-pulse per pixel). We found an optimum gating frequency range that maintains the viability of the cells while preserving a pre-set fluorescence signal of the acquired two-photon images. The neurons are imaged while under whole-cell patch, and the cell viability is monitored as a change in the membrane’s input resistance. PMID:26504651

A Compressive Sensing Approach for Glioma Margin Delineation Using Mass Spectrometry

PubMed Central

Gholami, Behnood; Agar, Nathalie Y. R.; Jolesz, Ferenc A.; Haddad, Wassim M.; Tannenbaum, Allen R.

2013-01-01

Surgery, and specifically, tumor resection, is the primary treatment for most patients suffering from brain tumors. Medical imaging techniques, and in particular, magnetic resonance imaging are currently used in diagnosis as well as image-guided surgery procedures. However, studies show that computed tomography and magnetic resonance imaging fail to accurately identify the full extent of malignant brain tumors and their microscopic infiltration. Mass spectrometry is a well-known analytical technique used to identify molecules in a given sample based on their mass. In a recent study, it is proposed to use mass spectrometry as an intraoperative tool for discriminating tumor and non-tumor tissue. Integration of mass spectrometry with the resection module allows for tumor resection and immediate molecular analysis. In this paper, we propose a framework for tumor margin delineation using compressive sensing. Specifically, we show that the spatial distribution of tumor cell concentration can be efficiently reconstructed and updated using mass spectrometry information from the resected tissue. In addition, our proposed framework is model-free, and hence, requires no prior information of spatial distribution of the tumor cell concentration. PMID:22255629

Roles for gut vagal sensory signals in determining energy availability and energy expenditure.

PubMed

Schwartz, Gary J

2018-08-15

The gut sensory vagus transmits a wide range of meal-related mechanical, chemical and gut peptide signals from gastrointestinal and hepatic tissues to the central nervous system at the level of the caudal brainstem. Results from studies using neurophysiological, behavioral physiological and metabolic approaches that challenge the integrity of this gut-brain axis support an important role for these gut signals in the negative feedback control of energy availability by limiting food intake during a meal. These experimental approaches have now been applied to identify important and unanticipated contributions of the vagal sensory gut-brain axis to the control of two additional effectors of overall energy balance: the feedback control of endogenous energy availability through hepatic glucose production and metabolism, and the control of energy expenditure through brown adipose tissue thermogenesis. Taken together, these studies reveal the pleiotropic influences of gut vagal meal-related signals on energy balance, and encourage experimental efforts aimed at understanding how the brainstem represents, organizes and coordinates gut vagal sensory signals with these three determinants of energy homeostasis. Copyright © 2018 Elsevier B.V. All rights reserved.

Assessing Amide Proton Transfer (APT) MRI Contrast Origins in 9 L Gliosarcoma in the Rat Brain Using Proteomic Analysis.

PubMed

Yan, Kun; Fu, Zongming; Yang, Chen; Zhang, Kai; Jiang, Shanshan; Lee, Dong-Hoon; Heo, Hye-Young; Zhang, Yi; Cole, Robert N; Van Eyk, Jennifer E; Zhou, Jinyuan

2015-08-01

To investigate the biochemical origin of the amide photon transfer (APT)-weighted hyperintensity in brain tumors. Seven 9 L gliosarcoma-bearing rats were imaged at 4.7 T. Tumor and normal brain tissue samples of equal volumes were prepared with a coronal rat brain matrix and a tissue biopsy punch. The total tissue protein and the cytosolic subproteome were extracted from both samples. Protein samples were analyzed using two-dimensional gel electrophoresis, and the proteins with significant abundance changes were identified by mass spectrometry. There was a significant increase in the cytosolic protein concentration in the tumor, compared to normal brain regions, but the total protein concentrations were comparable. The protein profiles of the tumor and normal brain tissue differed significantly. Six cytosolic proteins, four endoplasmic reticulum proteins, and five secreted proteins were considerably upregulated in the tumor. Our experiments confirmed an increase in the cytosolic protein concentration in tumors and identified several key proteins that may cause APT-weighted hyperintensity.

Dexamethasone increases production of C-type natriuretic peptide in the sheep brain.

PubMed

Wilson, Michele O; McNeill, Bryony A; Barrell, Graham K; Prickett, Timothy C R; Espiner, Eric A

2017-10-01

Although C-type natriuretic peptide (CNP) has high abundance in brain tissues and cerebrospinal fluid (CSF), the source and possible factors regulating its secretion within the central nervous system (CNS) are unknown. Here we report the dynamic effects of a single IV bolus of dexamethasone or saline solution on plasma, CSF, CNS and pituitary tissue content of CNP products in adult sheep, along with changes in CNP gene expression in selected tissues. Both CNP and NTproCNP (the amino-terminal product of proCNP) in plasma and CSF showed dose-responsive increases lasting 12-16 h after dexamethasone, whereas other natriuretic peptides were unaffected. CNS tissue concentrations of CNP and NTproCNP were increased by dexamethasone in all of the 12 regions examined. Abundance was highest in limbic tissues, pons and medulla oblongata. Relative to controls, CNP gene expression ( NPPC ) was upregulated by dexamethasone in 5 of 7 brain tissues examined. Patterns of responses differed in pituitary tissue. Whereas the abundance of CNP in both lobes of the pituitary gland greatly exceeded that of brain tissues, neither CNP nor NTproCNP concentration was affected by dexamethasone, despite an increase in NPPC expression. This is the first report of enhanced production and secretion of CNP in brain tissues in response to a corticosteroid. Activation of CNP secretion within CNS tissues by dexamethasone, not exhibited by other natriuretic peptides, suggests an important role for CNP in settings of acute stress. Differential findings in pituitary tissues likely relate to altered processing of proCNP storage and secretion. © 2017 Society for Endocrinology.

Bio-inspired hybrid microelectrodes: a hybrid solution to improve long-term performance of chronic intracortical implants.

PubMed

De Faveri, Sara; Maggiolini, Emma; Miele, Ermanno; De Angelis, Francesco; Cesca, Fabrizia; Benfenati, Fabio; Fadiga, Luciano

2014-01-01

The use of implants that allow chronic electrical stimulation and recording in the brain of human patients is currently limited by a series of events that cause the deterioration over time of both the electrode surface and the surrounding tissue. The main reason of failure is the tissue inflammatory reaction that eventually causes neuronal loss and glial encapsulation, resulting in a progressive increase of the electrode-electrolyte impedance. Here, we describe a new method to create bio-inspired electrodes to mimic the mechanical properties and biological composition of the host tissue. This combination has a great potential to increase the implant lifetime by reducing tissue reaction and improving electrical coupling. Our method implies coating the electrode with reprogrammed neural or glial cells encapsulated within a hydrogel layer. We chose fibrin as a hydrogel and primary hippocampal neurons or astrocytes from rat brain as cellular layer. We demonstrate that fibrin coating is highly biocompatible, forms uniform coatings of controllable thickness, does not alter the electrochemical properties of the microelectrode and allows good quality recordings. Moreover, it reduces the amount of host reactive astrocytes - over time - compared to a bare wire and is fully reabsorbed by the surrounding tissue within 7 days after implantation, avoiding the common problem of hydrogels swelling. Both astrocytes and neurons could be successfully grown onto the electrode surface within the fibrin hydrogel without altering the electrochemical properties of the microelectrode. This bio-hybrid device has therefore a good potential to improve the electrical integration at the neuron-electrode interface and support the long-term success of neural prostheses.

Neuroprotective effects of vagus nerve stimulation on traumatic brain injury

PubMed Central

Zhou, Long; Lin, Jinhuang; Lin, Junming; Kui, Guoju; Zhang, Jianhua; Yu, Yigang

2014-01-01

Previous studies have shown that vagus nerve stimulation can improve the prognosis of traumatic brain injury. The aim of this study was to elucidate the mechanism of the neuroprotective effects of vagus nerve stimulation in rabbits with brain explosive injury. Rabbits with brain explosive injury received continuous stimulation (10 V, 5 Hz, 5 ms, 20 minutes) of the right cervical vagus nerve. Tumor necrosis factor-α, interleukin-1β and interleukin-10 concentrations were detected in serum and brain tissues, and water content in brain tissues was measured. Results showed that vagus nerve stimulation could reduce the degree of brain edema, decrease tumor necrosis factor-α and interleukin-1β concentrations, and increase interleukin-10 concentration after brain explosive injury in rabbits. These data suggest that vagus nerve stimulation may exert neuroprotective effects against explosive injury via regulating the expression of tumor necrosis factor-α, interleukin-1β and interleukin-10 in the serum and brain tissue. PMID:25368644

MEASUREMENT OF SMALL MECHANICAL VIBRATIONS OF BRAIN TISSUE EXPOSED TO EXTREMELY-LOW-FREQUENCY ELECTRIC FIELDS

EPA Science Inventory

Electromagnetic fields can interact with biological tissue both electrically and mechanically. This study investigated the mechanical interaction between brain tissue and an extremely-low-frequency (ELF) electric field by measuring the resultant vibrational amplitude. The exposur...

Brain-shift compensation using intraoperative ultrasound and constraint-based biomechanical simulation.

PubMed

Morin, Fanny; Courtecuisse, Hadrien; Reinertsen, Ingerid; Le Lann, Florian; Palombi, Olivier; Payan, Yohan; Chabanas, Matthieu

2017-08-01

During brain tumor surgery, planning and guidance are based on preoperative images which do not account for brain-shift. However, this deformation is a major source of error in image-guided neurosurgery and affects the accuracy of the procedure. In this paper, we present a constraint-based biomechanical simulation method to compensate for craniotomy-induced brain-shift that integrates the deformations of the blood vessels and cortical surface, using a single intraoperative ultrasound acquisition. Prior to surgery, a patient-specific biomechanical model is built from preoperative images, accounting for the vascular tree in the tumor region and brain soft tissues. Intraoperatively, a navigated ultrasound acquisition is performed directly in contact with the organ. Doppler and B-mode images are recorded simultaneously, enabling the extraction of the blood vessels and probe footprint, respectively. A constraint-based simulation is then executed to register the pre- and intraoperative vascular trees as well as the cortical surface with the probe footprint. Finally, preoperative images are updated to provide the surgeon with images corresponding to the current brain shape for navigation. The robustness of our method is first assessed using sparse and noisy synthetic data. In addition, quantitative results for five clinical cases are provided, first using landmarks set on blood vessels, then based on anatomical structures delineated in medical images. The average distances between paired vessels landmarks ranged from 3.51 to 7.32 (in mm) before compensation. With our method, on average 67% of the brain-shift is corrected (range [1.26; 2.33]) against 57% using one of the closest existing works (range [1.71; 2.84]). Finally, our method is proven to be fully compatible with a surgical workflow in terms of execution times and user interactions. In this paper, a new constraint-based biomechanical simulation method is proposed to compensate for craniotomy-induced brain-shift. While being efficient to correct this deformation, the method is fully integrable in a clinical process. Copyright © 2017 Elsevier B.V. All rights reserved.

Recent Advances in Neural Electrode-Tissue Interfaces.

PubMed

Woeppel, Kevin; Yang, Qianru; Cui, Xinyan Tracy

2017-12-01

Neurotechnology is facing an exponential growth in the recent decades. Neural electrode-tissue interface research has been well recognized as an instrumental component of neurotechnology development. While satisfactory long-term performance was demonstrated in some applications, such as cochlear implants and deep brain stimulators, more advanced neural electrode devices requiring higher resolution for single unit recording or microstimulation still face significant challenges in reliability and longevity. In this article, we review the most recent findings that contribute to our current understanding of the sources of poor reliability and longevity in neural recording or stimulation, including the material failure, biological tissue response and the interplay between the two. The newly developed characterization tools are introduced from electrophysiology models, molecular and biochemical analysis, material characterization to live imaging. The effective strategies that have been applied to improve the interface are also highlighted. Finally, we discuss the challenges and opportunities in improving the interface and achieving seamless integration between the implanted electrodes and neural tissue both anatomically and functionally.

Detection of radiation-induced brain necrosis in live rats using label-free time-resolved fluorescence spectroscopy (TRFS) (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hartl, Brad A.; Ma, Htet S. W.; Sridharan, Shamira; Hansen, Katherine; Klich, Melanie; Perks, Julian; Kent, Michael; Kim, Kyoungmi; Fragoso, Ruben; Marcu, Laura

2017-02-01

Differentiating radiation-induced necrosis from recurrent tumor in the brain remains a significant challenge to the neurosurgeon. Clinical imaging modalities are not able to reliably discriminate the two tissue types, making biopsy location selection and surgical management difficult. Label-free fluorescence lifetime techniques have previously been shown to be able to delineate human brain tumor from healthy tissues. Thus, fluorescence lifetime techniques represent a potential means to discriminate the two tissues in real-time during surgery. This study aims to characterize the endogenous fluorescence lifetime signatures from radiation induced brain necrosis in a tumor-free rat model. Fischer rats received a single fraction of 60 Gy of radiation to the right hemisphere using a linear accelerator. Animals underwent a terminal live surgery after gross necrosis had developed, as verified with MRI. During surgery, healthy and necrotic brain tissue was measured with a fiber optic needle connected to a multispectral fluorescence lifetime system. Measurements of the necrotic tissue showed a 48% decrease in intensity and 20% increase in lifetimes relative to healthy tissue. Using a support vector machine classifier and leave-one-out validation technique, the necrotic tissue was correctly classified with 94% sensitivity and 97% specificity. Spectral contribution analysis also confirmed that the primary source of fluorescence contrast lies within the redox and bound-unbound population shifts of nicotinamide adenine dinucleotide. A clinical trial is presently underway to measure these tissue types in humans. These results show for the first time that radiation-induced necrotic tissue in the brain contains significantly different metabolic signatures that are detectable with label-free fluorescence lifetime techniques.

Light interference as a possible stressor altering HSP70 and its gene expression levels in brain and hepatic tissues of golden spiny mice.

PubMed

Ashkenazi, Lilach; Haim, Abraham

2012-11-15

Light at night and light interference (LI) disrupt the natural light:dark cycle, causing alterations at physiological and molecular levels, partly by suppressing melatonin (MLT) secretion at night. Heat shock proteins (HSPs) can be activated in response to environmental changes. We assessed changes in gene expression and protein level of HSP70 in brain and hepatic tissues of golden spiny mice (Acomys russatus) acclimated to LI for two (SLI), seven (MLI) and 21 nights (LLI). The effect of MLT treatment on LI-mice was also assessed. HSP70 levels increased in brain and hepatic tissues after SLI, whereas after MLI and LLI, HSP70 decreased to control levels. Changes in HSP70 levels as a response to MLT occurred after SLI only in hepatic tissue. However, hsp70 expression following SLI increased in brain tissue, but not in hepatic tissue. MLT treatment and SLI caused a decrease in hsp70 levels in brain tissue and an increase in hsp70 in hepatic tissue. SLI acclimation elicited a stress response in A. russatus, as expressed by increased HSP70 levels and gene expression. Longer acclimation decreases protein and gene expression to their control levels. We conclude that for brain and hepatic tissues of A. russatus, LI is a short-term stressor. Our results also revealed that A. russatus can acclimate to LI, possibly because of its circadian system plasticity, which allows it to behave both as a nocturnal and as a diurnal rodent. To the best of our knowledge, this is the first study showing the effect of LI as a stressor at the cellular level, by activating HSP70.

Distribution of lead in the brain tissues from DNTC patients using synchrotron radiation microbeams

NASA Astrophysics Data System (ADS)

Ide-Ektessabi, Ari; Ota, Yukihide; Ishihara, Ryoko; Mizuno, Yutaka; Takeuchi, Tohru

2005-12-01

Diffuse neurofibrillary tangles with calcification (DNTC) is a form of dementia with certain characteristics. Its pathology is characterized by cerebrum atrophy, calcification on globus pallidus and dentate nucleus and diffuse neurofibrillary tangles without senile plaques. In the present study brain tissues were prepared from patients with patients DNTC, calcified and non-calcified Alzheimer's disease (AD) patients. The brain tissues were examined non-destructively by X-ray fluorescence (XRF) spectroscopy using synchrotron radiation (SR) microbeams for trace metallic elements Ca, Fe, Cu, Zn and Pb. The XRF analysis showed that there were Pb concentrations in the calcified areas in the brain tissues with both DNTC and AD but there was none in those with non-calcified AD.

Brain Sex Matters: estrogen in cognition and Alzheimer’s disease

PubMed Central

Li, Rena; Cui, Jie; Shen, Yong

2014-01-01

Estrogens are the primary female sex hormones and play important roles in both reproductive and non-reproductive systems. Estrogens can be synthesized in non-reproductive tissues such as liver, heart, muscle, bone and the brain. During the past decade, increasing evidence suggests that brain estrogen can not only be synthesized by neurons, but also by astrocytes. Brain estrogen also works locally at the site of synthesis in paracrine and/or intracrine fashion to maintain important tissue-specific functions. Here, we will focus on the biology of brain estrogen and its impact on cognitive function and Alzheimer’s disease. This comprehensive review provides new insights into brain estrogens by presenting a better understanding of the tissue-specific estrogen effects and their roles in healthy ageing and cognitive function. PMID:24418360

Expression of hypoxia-inducible carbonic anhydrases in brain tumors

PubMed Central

Proescholdt, Martin A.; Mayer, Christina; Kubitza, Marion; Schubert, Thomas; Liao, Shu-Yuan; Stanbridge, Eric J.; Ivanov, Sergey; Oldfield, Edward H.; Brawanski, Alexander; Merrill, Marsha J.

2005-01-01

Malignant brain tumors exhibit distinct metabolic characteristics. Despite high levels of lactate, the intracellular pH of brain tumors is more alkaline than normal brain. Additionally, with increasing malignancy, brain tumors display intratumoral hypoxia. Carbonic anhydrase (CA) IX and XII are transmembrane isoenzymes that are induced by tissue hypoxia. They participate in regulation of pH homeostasis by catalyzing the reversible hydration of carbon dioxide. The aim of our study was to investigate whether brain tumors of different histology and grade of malignancy express elevated levels of CA IX and XII as compared to normal brain. We analyzed 120 tissue specimens from brain tumors (primary and metastatic) and normal brain for CA IX and XII expression by immunohistochemistry, Western blot, and in situ hybridization. Whereas normal brain tissue showed minimal levels of CA IX and XII expression, expression in tumors was found to be upregulated with increased level of malignancy. Hemangioblastomas, from patients with von Hippel–Lindau disease, also displayed high levels of CA IX and XII expression. Comparison of CA IX and XII staining with HIF-1α staining revealed a similar microanatomical distribution, indicating hypoxia as a major, but not the only, induction factor. The extent of CA IX and XII staining correlated with cell proliferation, as indicated by Ki67 labeling. The results demonstrate that CA IX and XII are upregulated in intrinsic and metastatic brain tumors as compared to normal brain tissue. This may contribute to the management of tumor-specific acid load and provide a therapeutic target. PMID:16212811

Dye-enhanced multimodal confocal imaging as a novel approach to intraoperative diagnosis of brain tumors.

PubMed

Snuderl, Matija; Wirth, Dennis; Sheth, Sameer A; Bourne, Sarah K; Kwon, Churl-Su; Ancukiewicz, Marek; Curry, William T; Frosch, Matthew P; Yaroslavsky, Anna N

2013-01-01

Intraoperative diagnosis plays an important role in accurate sampling of brain tumors, limiting the number of biopsies required and improving the distinction between brain and tumor. The goal of this study was to evaluate dye-enhanced multimodal confocal imaging for discriminating gliomas from nonglial brain tumors and from normal brain tissue for diagnostic use. We investigated a total of 37 samples including glioma (13), meningioma (7), metastatic tumors (9) and normal brain removed for nontumoral indications (8). Tissue was stained in 0.05 mg/mL aqueous solution of methylene blue (MB) for 2-5 minutes and multimodal confocal images were acquired using a custom-built microscope. After imaging, tissue was formalin fixed and paraffin embedded for standard neuropathologic evaluation. Thirteen pathologists provided diagnoses based on the multimodal confocal images. The investigated tumor types exhibited distinctive and complimentary characteristics in both the reflectance and fluorescence responses. Images showed distinct morphological features similar to standard histology. Pathologists were able to distinguish gliomas from normal brain tissue and nonglial brain tumors, and to render diagnoses from the images in a manner comparable to haematoxylin and eosin (H&E) slides. These results confirm the feasibility of multimodal confocal imaging for intravital intraoperative diagnosis. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

NASA Robotic Neurosurgery Testbed

NASA Technical Reports Server (NTRS)

Mah, Robert

1997-01-01

The detection of tissue interface (e.g., normal tissue, cancer, tumor) has been limited clinically to tactile feedback, temperature monitoring, and the use of a miniature ultrasound probe for tissue differentiation during surgical operations, In neurosurgery, the needle used in the standard stereotactic CT or MRI guided brain biopsy provides no information about the tissue being sampled. The tissue sampled depends entirely upon the accuracy with which the localization provided by the preoperative CT or MRI scan is translated to the intracranial biopsy site. In addition, no information about the tissue being traversed by the needle (e.g., a blood vessel) is provided. Hemorrhage due to the biopsy needle tearing a blood vessel within the brain is the most devastating complication of stereotactic CT/MRI guided brain biopsy. A robotic neurosurgery testbed has been developed at NASA Ames Research Center as a spin-off of technologies from space, aeronautics and medical programs. The invention entitled "Robotic Neurosurgery Leading to Multimodality Devices for Tissue Identification" is nearing a state ready for commercialization. The devices will: 1) improve diagnostic accuracy and precision of general surgery, with near term emphasis on stereotactic brain biopsy, 2) automate tissue identification, with near term emphasis on stereotactic brain biopsy, to permit remote control of the procedure, and 3) reduce morbidity for stereotactic brain biopsy. The commercial impact from this work is the potential development of a whole new generation of smart surgical tools to increase the safety, accuracy and efficiency of surgical procedures. Other potential markets include smart surgical tools for tumor ablation in neurosurgery, general exploratory surgery, prostate cancer surgery, and breast cancer surgery.

NASA Robotic Neurosurgery Testbed

NASA Technical Reports Server (NTRS)

Mah, Robert

1997-01-01

The detection of tissue interface (e.g., normal tissue, cancer, tumor) has been limited clinically to tactile feedback, temperature monitoring, and the use of a miniature ultrasound probe for tissue differentiation during surgical operations. In neurosurgery, the needle used in the standard stereotactic CT (Computational Tomography) or MRI (Magnetic Resonance Imaging) guided brain biopsy provides no information about the tissue being sampled. The tissue sampled depends entirely upon the accuracy with which the localization provided by the preoperative CT or MRI scan is translated to the intracranial biopsy site. In addition, no information about the tissue being traversed by the needle (e.g., a blood vessel) is provided. Hemorrhage due to the biopsy needle tearing a blood vessel within the brain is the most devastating complication of stereotactic CT/MRI guided brain biopsy. A robotic neurosurgery testbed has been developed at NASA Ames Research Center as a spin-off of technologies from space, aeronautics and medical programs. The invention entitled 'Robotic Neurosurgery Leading to Multimodality Devices for Tissue Identification' is nearing a state ready for commercialization. The devices will: 1) improve diagnostic accuracy and precision of general surgery, with near term emphasis on stereotactic brain biopsy, 2) automate tissue identification, with near term emphasis on stereotactic brain biopsy, to permit remote control of the procedure, and 3) reduce morbidity for stereotactic brain biopsy. The commercial impact from this work is the potential development of a whole new generation of smart surgical tools to increase the safety, accuracy and efficiency of surgical procedures. Other potential markets include smart surgical tools for tumor ablation in neurosurgery, general exploratory surgery, prostate cancer surgery, and breast cancer surgery.

Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder

PubMed Central

Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

2016-01-01

Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain. PMID:27057543

Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder.

PubMed

Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

2016-01-01

Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain.

[Effects of Geometrical Dimensions and Material Properties on the Rotation Characteristics of Head].

PubMed

Chen, Yue; Cui, Shihai; Li, Haiyan; Ruan, Shijie

2016-08-01

The validated finite element head model(FEHM)of a 3-year-old child,a 6-year-old child and a 50 th percentile adult were used to investigate the effects of head dimension and material parameters of brain tissues on the head rotational responses based on experimental design.Results showed that the effects of head dimension and directions of rotation on the head rotational responses were not significant under the same rotational loading condition,and the same results appeared in the viscoelastic material parameters of brain tissues.However,the head rotational responses were most sensitive to the shear modulus(G)of brain tissues relative to decay constant(β)and bulk modulus(K).Therefore,the selection of material parameters of brain tissues is most important to the accuracy of simulation results,especially in the study of brain injury criterion under the rotational loading conditions.

The biochemical, nanomechanical and chemometric signatures of brain cancer

NASA Astrophysics Data System (ADS)

Abramczyk, Halina; Imiela, Anna

2018-01-01

Raman spectroscopy and imaging combined with AFM topography and mechanical indentation by AFM have been shown to be an effective tool for analysis and discrimination of human brain tumors from normal structures. Raman methods have potential to be applied in clinical practice as they allow for identification of tumor margins during surgery. In this study, we investigate medulloblastoma (grade IV WHO) (n = 5) and the tissue from the negative margins used as normal controls. We compare a high grade medulloblastoma (IV grade), and non-tumor samples from human central nervous system (CNS) tissue. Based on the properties of the Raman vibrational spectra and Raman images we provide a real-time feedback that is label-free method to monitor tumor metabolism that reveals reprogramming of biosynthesis of lipids, and proteins. We have found that the high-grade tumors of central nervous system (medulloblastoma) exhibit enhanced level of β-sheet conformation and down-regulated level of α-helix conformation when comparing against normal tissue. We have shown that the ratio of Raman intensities I2930/I2845 at 2930 and 2845 cm- 1 is a good source of information on the ratio of lipid and protein contents. We have found that the ratio reflects the lipid and protein contents of tumorous brain tissue compared to the non-tumor tissue. Almost all brain tumors have the Raman intensity ratios significantly higher (1.99 ± 0.026) than that found in non-tumor brain tissue, which is 1.456 ± 0.02, and indicates that the relative amount of lipids compared to proteins is significantly higher in the normal brain tissue. Mechanical indentation using AFM on sliced human brain tissues (medulloblastoma, grade IV) revealed that the mechanical properties of this tissue are strongly heterogeneous, between 1.8 and 75.7 kPa, and the mean of 27.16 kPa. The sensitivity and specificity obtained directly from PLSDA and cross validation gives a sensitivity and specificity of 98.5% and 96% and 96.3% and 92% for cross-validation, respectively. The high sensitivity and specificity demonstrates usefulness for a proper decision for a Raman diagnostic test on biochemical alterations monitored by Raman spectroscopy related to brain cancer development.

Age dependence of dielectric properties of bovine brain and ocular tissues in the frequency range of 400 MHz to 18 GHz

NASA Astrophysics Data System (ADS)

Schmid, Gernot; Überbacher, Richard

2005-10-01

In order to identify possible age-dependent dielectric properties of brain and eye tissues in the frequency range of 400 MHz to 18 GHz, measurements on bovine grey and white matter as well as on cornea, lens (cortical) and the vitreous body were performed using a commercially available open-ended coaxial probe and a computer-controlled vector network analyser. Freshly excised tissues of 52 animals of two age groups (42 adult animals, i.e. 16-24 month old and 10 young animals, i.e. 4-6 month old calves) were examined within 8 min (brain tissue) and 15 min (eye tissue), respectively, of the animals' death. Tissue temperatures for the measurements were 32 ± 1 °C and 25 ± 1 °C for brain and eye tissues, respectively. Statistical analysis of the measured data revealed significant differences in the dielectric properties of white matter and cortical lens tissue between the adult and the young group. In the case of white matter the mean values of conductivity and permittivity of young tissue were 15%-22% and 12%-15%, respectively, higher compared to the adult tissue in the considered frequency range. Similarly, young cortical lens tissue was 25%-76% higher in conductivity and 27%-39% higher in permittivity than adult cortical lens tissue.

Zika Virus RNA Replication and Persistence in Brain and Placental Tissue

PubMed Central

Rabeneck, Demi B.; Martines, Roosecelis B.; Reagan-Steiner, Sarah; Ermias, Yokabed; Estetter, Lindsey B.C.; Suzuki, Tadaki; Ritter, Jana; Keating, M. Kelly; Hale, Gillian; Gary, Joy; Muehlenbachs, Atis; Lambert, Amy; Lanciotti, Robert; Oduyebo, Titilope; Meaney-Delman, Dana; Bolaños, Fernando; Saad, Edgar Alberto Parra; Shieh, Wun-Ju; Zaki, Sherif R.

2017-01-01

Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections. PMID:27959260

Gene expression changes with age in skin, adipose tissue, blood and brain.

PubMed

Glass, Daniel; Viñuela, Ana; Davies, Matthew N; Ramasamy, Adaikalavan; Parts, Leopold; Knowles, David; Brown, Andrew A; Hedman, Asa K; Small, Kerrin S; Buil, Alfonso; Grundberg, Elin; Nica, Alexandra C; Di Meglio, Paola; Nestle, Frank O; Ryten, Mina; Durbin, Richard; McCarthy, Mark I; Deloukas, Panagiotis; Dermitzakis, Emmanouil T; Weale, Michael E; Bataille, Veronique; Spector, Tim D

2013-07-26

Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age. Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues. Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases.

In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

PubMed

Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

2016-05-01

High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.

Long-term exposure of mice to nucleoside analogues disrupts mitochondrial DNA maintenance in cortical neurons.

PubMed

Zhang, Yulin; Song, Fengli; Gao, Ziyun; Ding, Wei; Qiao, Luxin; Yang, Sufang; Chen, Xi; Jin, Ronghua; Chen, Dexi

2014-01-01

Nucleoside analogue reverse transcriptase inhibitor (NRTI), an integral component of highly active antiretroviral therapy (HAART), was widely used to inhibit HIV replication. Long-term exposure to NRTIs can result in mitochondrial toxicity which manifests as lipoatrophy, lactic acidosis, cardiomyopathy and myopathy, as well as polyneuropathy. But the cerebral neurotoxicity of NRTIs is still not well known partly due to the restriction of blood-brain barrier (BBB) and the complex microenvironment of the central nervous system (CNS). In this study, the Balb/c mice were administered 50 mg/kg stavudine (D4T), 100 mg/kg zidovudine (AZT), 50 mg/kg lamivudine (3TC) or 50 mg/kg didanosine (DDI) per day by intraperitoneal injection, five days per week for one or four months, and primary cortical neurons were cultured and exposed to 25 µM D4T, 50 µM AZT, 25 µM 3TC or 25 µM DDI for seven days. Then, single neuron was captured from mouse cerebral cortical tissues by laser capture microdissection. Mitochondrial DNA (mtDNA) levels of the primary cultured cortical neurons, and captured neurons or glial cells, and the tissues of brains and livers and muscles were analyzed by relative quantitative real-time PCR. The data showed that mtDNA did not lose in both NRTIs exposed cultured neurons and one month NRTIs treated mouse brains. In four months NRTIs treated mice, brain mtDNA levels remained unchanged even if the mtDNA levels of liver (except for 3TC) and muscle significantly decreased. However, mtDNA deletion was significantly higher in the captured neurons from mtDNA unchanged brains. These results suggest that long-term exposure to NRTIs can result in mtDNA deletion in mouse cortical neurons.

Combined ultrasound and MR imaging to guide focused ultrasound therapies in the brain

NASA Astrophysics Data System (ADS)

Arvanitis, Costas D.; Livingstone, Margaret S.; McDannold, Nathan

2013-07-01

Several emerging therapies with potential for use in the brain, harness effects produced by acoustic cavitation—the interaction between ultrasound and microbubbles either generated during sonication or introduced into the vasculature. Systems developed for transcranial MRI-guided focused ultrasound (MRgFUS) thermal ablation can enable their clinical translation, but methods for real-time monitoring and control are currently lacking. Acoustic emissions produced during sonication can provide information about the location, strength and type of the microbubble oscillations within the ultrasound field, and they can be mapped in real-time using passive imaging approaches. Here, we tested whether such mapping can be achieved transcranially within a clinical brain MRgFUS system. We integrated an ultrasound imaging array into the hemisphere transducer of the MRgFUS device. Passive cavitation maps were obtained during sonications combined with a circulating microbubble agent at 20 targets in the cingulate cortex in three macaques. The maps were compared with MRI-evident tissue effects. The system successfully mapped microbubble activity during both stable and inertial cavitation, which was correlated with MRI-evident transient blood-brain barrier disruption and vascular damage, respectively. The location of this activity was coincident with the resulting tissue changes within the expected resolution limits of the system. While preliminary, these data clearly demonstrate, for the first time, that it is possible to construct maps of stable and inertial cavitation transcranially, in a large animal model, and under clinically relevant conditions. Further, these results suggest that this hybrid ultrasound/MRI approach can provide comprehensive guidance for targeted drug delivery via blood-brain barrier disruption and other emerging ultrasound treatments, facilitating their clinical translation. We anticipate that it will also prove to be an important research tool that will further the development of a broad range of microbubble-enhanced therapies.

in vivo quantification of white matter microstructure for use in aging: A focus on two emerging techniques

PubMed Central

Lamar, Melissa; Zhou, Xiaohong Joe; Charlton, Rebecca A.; Dean, Douglas; Little, Deborah; Deoni, Sean C

2013-01-01

Human brain imaging has seen many advances in the quantification of white matter in vivo. For example, these advances have revealed the association between white matter damage and vascular disease as well as their impact on risk for and development of dementia and depression in an aging population. Current neuroimaging methods to quantify white matter damage provide a foundation for understanding such age-related neuropathology; however, these methods are not as adept at determining the underlying microstructural abnormalities signaling at risk tissue or driving white matter damage in the aging brain. This review will begin with a brief overview of the use of diffusion tensor imaging (DTI) in understanding white matter alterations in aging before focusing in more detail on select advances in both diffusion-based methods and multi-component relaxometry techniques for imaging white matter microstructural integrity within myelin sheaths and the axons they encase. While DTI greatly extended the field of white matter interrogation, these more recent technological advances will add clarity to the underlying microstructural mechanisms that contribute to white matter damage. More specifically, the methods highlighted in this review may prove more sensitive (and specific) for determining the contribution of myelin versus axonal integrity to the aging of white matter in brain. PMID:24080382

Evidence for brain glucose dysregulation in Alzheimer's disease.

PubMed

An, Yang; Varma, Vijay R; Varma, Sudhir; Casanova, Ramon; Dammer, Eric; Pletnikova, Olga; Chia, Chee W; Egan, Josephine M; Ferrucci, Luigi; Troncoso, Juan; Levey, Allan I; Lah, James; Seyfried, Nicholas T; Legido-Quigley, Cristina; O'Brien, Richard; Thambisetty, Madhav

2018-03-01

It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose. Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations. Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may begin several years before the onset of clinical symptoms. Copyright © 2017 the Alzheimer's Association. All rights reserved.

Where the thoughts dwell: the physiology of neuronal-glial "diffuse neural net".

PubMed

Verkhratsky, Alexei; Parpura, Vladimir; Rodríguez, José J

2011-01-07

The mechanisms underlying the production of thoughts by exceedingly complex cellular networks that construct the human brain constitute the most challenging problem of natural sciences. Our understanding of the brain function is very much shaped by the neuronal doctrine that assumes that neuronal networks represent the only substrate for cognition. These neuronal networks however are embedded into much larger and probably more complex network formed by neuroglia. The latter, although being electrically silent, employ many different mechanisms for intercellular signalling. It appears that astrocytes can control synaptic networks and in such a capacity they may represent an integral component of the computational power of the brain rather than being just brain "connective tissue". The fundamental question of whether neuroglia is involved in cognition and information processing remains, however, open. Indeed, a remarkable increase in the number of glial cells that distinguishes the human brain can be simply a result of exceedingly high specialisation of the neuronal networks, which delegated all matters of survival and maintenance to the neuroglia. At the same time potential power of analogue processing offered by internally connected glial networks may represent the alternative mechanism involved in cognition. Copyright © 2010 Elsevier B.V. All rights reserved.

Laser Desorption/Ionization Mass Spectrometric Imaging of Endogenous Lipids from Rat Brain Tissue Implanted with Silver Nanoparticles

NASA Astrophysics Data System (ADS)

Muller, Ludovic; Baldwin, Kathrine; Barbacci, Damon C.; Jackson, Shelley N.; Roux, Aurélie; Balaban, Carey D.; Brinson, Bruce E.; McCully, Michael I.; Lewis, Ernest K.; Schultz, J. Albert; Woods, Amina S.

2017-08-01

Mass spectrometry imaging (MSI) of tissue implanted with silver nanoparticulate (AgNP) matrix generates reproducible imaging of lipids in rodent models of disease and injury. Gas-phase production and acceleration of size-selected 8 nm AgNP is followed by controlled ion beam rastering and soft landing implantation of 500 eV AgNP into tissue. Focused 337 nm laser desorption produces high quality images for most lipid classes in rat brain tissue (in positive mode: galactoceramides, diacylglycerols, ceramides, phosphatidylcholines, cholesteryl ester, and cholesterol, and in negative ion mode: phosphatidylethanolamides, sulfatides, phosphatidylinositol, and sphingomyelins). Image reproducibility in serial sections of brain tissue is achieved within <10% tolerance by selecting argentated instead of alkali cationized ions. The imaging of brain tissues spotted with pure standards was used to demonstrate that Ag cationized ceramide and diacylglycerol ions are from intact, endogenous species. In contrast, almost all Ag cationized fatty acid ions are a result of fragmentations of numerous lipid types having the fatty acid as a subunit. Almost no argentated intact fatty acid ions come from the pure fatty acid standard on tissue.

In vivo three-photon microscopy of subcortical structures within an intact mouse brain

NASA Astrophysics Data System (ADS)

Horton, Nicholas G.; Wang, Ke; Kobat, Demirhan; Clark, Catharine G.; Wise, Frank W.; Schaffer, Chris B.; Xu, Chris

2013-03-01

Two-photon fluorescence microscopy enables scientists in various fields including neuroscience, embryology and oncology to visualize in vivo and ex vivo tissue morphology and physiology at a cellular level deep within scattering tissue. However, tissue scattering limits the maximum imaging depth of two-photon fluorescence microscopy to the cortical layer within mouse brain, and imaging subcortical structures currently requires the removal of overlying brain tissue or the insertion of optical probes. Here, we demonstrate non-invasive, high-resolution, in vivo imaging of subcortical structures within an intact mouse brain using three-photon fluorescence microscopy at a spectral excitation window of 1,700 nm. Vascular structures as well as red fluorescent protein-labelled neurons within the mouse hippocampus are imaged. The combination of the long excitation wavelength and the higher-order nonlinear excitation overcomes the limitations of two-photon fluorescence microscopy, enabling biological investigations to take place at a greater depth within tissue.

EphrinB3 restricts endogenous neural stem cell migration after traumatic brain injury.

PubMed

Dixon, Kirsty J; Mier, Jose; Gajavelli, Shyam; Turbic, Alisa; Bullock, Ross; Turnley, Ann M; Liebl, Daniel J

2016-11-01

Traumatic brain injury (TBI) leads to a series of pathological events that can have profound influences on motor, sensory and cognitive functions. Conversely, TBI can also stimulate neural stem/progenitor cell proliferation leading to increased numbers of neuroblasts migrating outside their restrictive neurogenic zone to areas of damage in support of tissue integrity. Unfortunately, the factors that regulate migration are poorly understood. Here, we examine whether ephrinB3 functions to restrict neuroblasts from migrating outside the subventricular zone (SVZ) and rostral migratory stream (RMS). We have previously shown that ephrinB3 is expressed in tissues surrounding these regions, including the overlying corpus callosum (CC), and is reduced after controlled cortical impact (CCI) injury. Our current study takes advantage of ephrinB3 knockout mice to examine the influences of ephrinB3 on neuroblast migration into CC and cortex tissues after CCI injury. Both injury and/or ephrinB3 deficiency led to increased neuroblast numbers and enhanced migration outside the SVZ/RMS zones. Application of soluble ephrinB3-Fc molecules reduced neuroblast migration into the CC after injury and limited neuroblast chain migration in cultured SVZ explants. Our findings suggest that ephrinB3 expression in tissues surrounding neurogenic regions functions to restrict neuroblast migration outside the RMS by limiting chain migration. Copyright © 2016 Michael Boutros, German Cancer Research Center, Heidelberg, Germany. Published by Elsevier B.V. All rights reserved.

The national DBS brain tissue network pilot study: need for more tissue and more standardization.

PubMed

Vedam-Mai, V; Krock, N; Ullman, M; Foote, K D; Shain, W; Smith, K; Yachnis, A T; Steindler, D; Reynolds, B; Merritt, S; Pagan, F; Marjama-Lyons, J; Hogarth, P; Resnick, A S; Zeilman, P; Okun, M S

2011-08-01

Over 70,000 DBS devices have been implanted worldwide; however, there remains a paucity of well-characterized post-mortem DBS brains available to researchers. We propose that the overall understanding of DBS can be improved through the establishment of a Deep Brain Stimulation-Brain Tissue Network (DBS-BTN), which will further our understanding of DBS and brain function. The objectives of the tissue bank are twofold: (a) to provide a complete (clinical, imaging and pathological) database for DBS brain tissue samples, and (b) to make available DBS tissue samples to researchers, which will help our understanding of disease and underlying brain circuitry. Standard operating procedures for processing DBS brains were developed as part of the pilot project. Complete data files were created for individual patients and included demographic information, clinical information, imaging data, pathology, and DBS lead locations/settings. 19 DBS brains were collected from 11 geographically dispersed centers from across the U.S. The average age at the time of death was 69.3 years (51-92, with a standard deviation or SD of 10.13). The male:female ratio was almost 3:1. Average post-mortem interval from death to brain collection was 10.6 h (SD of 7.17). The DBS targets included: subthalamic nucleus, globus pallidus interna, and ventralis intermedius nucleus of the thalamus. In 16.7% of cases the clinical diagnosis failed to match the pathological diagnosis. We provide neuropathological findings from the cohort, and perilead responses to DBS. One of the most important observations made in this pilot study was the missing data, which was approximately 25% of all available data fields. Preliminary results demonstrated the feasibility and utility of creating a National DBS-BTN resource for the scientific community. We plan to improve our techniques to remedy omitted clinical/research data, and expand the Network to include a larger donor pool. We will enhance sample preparation to facilitate advanced molecular studies and progenitor cell retrieval.

Organization of brain tissue - Is the brain a noisy processor.

NASA Technical Reports Server (NTRS)

Adey, W. R.

1972-01-01

This paper presents some thoughts on functional organization in cerebral tissue. 'Spontaneous' wave and unit firing are considered as essential phenomena in the handling of information. Various models are discussed which have been suggested to describe the pseudorandom behavior of brain cells, leading to a view of the brain as an information processor and its role in learning, memory, remembering and forgetting.

Brain extraction from normal and pathological images: A joint PCA/Image-Reconstruction approach.

PubMed

Han, Xu; Kwitt, Roland; Aylward, Stephen; Bakas, Spyridon; Menze, Bjoern; Asturias, Alexander; Vespa, Paul; Van Horn, John; Niethammer, Marc

2018-08-01

Brain extraction from 3D medical images is a common pre-processing step. A variety of approaches exist, but they are frequently only designed to perform brain extraction from images without strong pathologies. Extracting the brain from images exhibiting strong pathologies, for example, the presence of a brain tumor or of a traumatic brain injury (TBI), is challenging. In such cases, tissue appearance may substantially deviate from normal tissue appearance and hence violates algorithmic assumptions for standard approaches to brain extraction; consequently, the brain may not be correctly extracted. This paper proposes a brain extraction approach which can explicitly account for pathologies by jointly modeling normal tissue appearance and pathologies. Specifically, our model uses a three-part image decomposition: (1) normal tissue appearance is captured by principal component analysis (PCA), (2) pathologies are captured via a total variation term, and (3) the skull and surrounding tissue is captured by a sparsity term. Due to its convexity, the resulting decomposition model allows for efficient optimization. Decomposition and image registration steps are alternated to allow statistical modeling of normal tissue appearance in a fixed atlas coordinate system. As a beneficial side effect, the decomposition model allows for the identification of potentially pathological areas and the reconstruction of a quasi-normal image in atlas space. We demonstrate the effectiveness of our approach on four datasets: the publicly available IBSR and LPBA40 datasets which show normal image appearance, the BRATS dataset containing images with brain tumors, and a dataset containing clinical TBI images. We compare the performance with other popular brain extraction models: ROBEX, BEaST, MASS, BET, BSE and a recently proposed deep learning approach. Our model performs better than these competing approaches on all four datasets. Specifically, our model achieves the best median (97.11) and mean (96.88) Dice scores over all datasets. The two best performing competitors, ROBEX and MASS, achieve scores of 96.23/95.62 and 96.67/94.25 respectively. Hence, our approach is an effective method for high quality brain extraction for a wide variety of images. Copyright © 2018 Elsevier Inc. All rights reserved.

Relationship between concentrations of lutein and StARD3 among pediatric and geriatric human brain tissue

USDA-ARS?s Scientific Manuscript database

Lutein, a dietary carotenoid, selectively accumulates in human retina and brain. While many epidemiological studies show evidence of a relationship between lutein status and cognitive health, lutein's selective uptake in human brain tissue and its potential function in early neural development and c...

Time-resolved fluorescence spectroscopy of human brain tumors

NASA Astrophysics Data System (ADS)

Marcu, Laura; Thompson, Reid C.; Garde, Smita; Sedrak, Mark; Black, Keith L.; Yong, William H.

2002-05-01

Fluorescence spectroscopy of the endogenous emission of brain tumors has been researched as a potentially important method for the intraoperative localization of brain tumor margins. In this study, we investigate the use of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) for demarcation of primary brain tumors by studying the time-resolved spectra of gliomas of different histologic grades. Time-resolved fluorescence (3 ns, 337 nm excitation) from excised human brain tumor show differences between the time-resolved emission of malignant glioma and normal brain tissue (gray and white matter). Our findings suggest that brain tumors can be differentiated from normal brain tissue based upon unique time-resolved fluorescence signature.

Medical diagnosis imaging systems: image and signal processing applications aided by fuzzy logic

NASA Astrophysics Data System (ADS)

Hata, Yutaka

2010-04-01

First, we describe an automated procedure for segmenting an MR image of a human brain based on fuzzy logic for diagnosing Alzheimer's disease. The intensity thresholds for segmenting the whole brain of a subject are automatically determined by finding the peaks of the intensity histogram. After these thresholds are evaluated in a region growing, the whole brain can be identified. Next, we describe a procedure for decomposing the obtained whole brain into the left and right cerebral hemispheres, the cerebellum and the brain stem. Our method then identified the whole brain, the left cerebral hemisphere, the right cerebral hemisphere, the cerebellum and the brain stem. Secondly, we describe a transskull sonography system that can visualize the shape of the skull and brain surface from any point to examine skull fracture and some brain diseases. We employ fuzzy signal processing to determine the skull and brain surface. The phantom model, the animal model with soft tissue, the animal model with brain tissue, and a human subjects' forehead is applied in our system. The all shapes of the skin surface, skull surface, skull bottom, and brain tissue surface are successfully determined.

Non-destructive optical clearing technique enhances optical coherence tomography (OCT) for real-time, 3D histomorphometry of brain tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Paul, Akshay; Chang, Theodore H.; Chou, Li-Dek; Ramalingam, Tirunelveli S.

2016-03-01

Evaluation of neurodegenerative disease often requires examination of brain morphology. Volumetric analysis of brain regions and structures can be used to track developmental changes, progression of disease, and the presence of transgenic phenotypes. Current standards for microscopic investigation of brain morphology are limited to detection of superficial structures at a maximum depth of 300μm. While histological techniques can provide detailed cross-sections of brain structures, they require complicated tissue preparation and the ultimate destruction of the sample. A non-invasive, label-free imaging modality known as Optical Coherence Tomography (OCT) can produce 3-dimensional reconstructions through high-speed, cross-sectional scans of biological tissue. Although OCT allows for the preservation of intact samples, the highly scattering and absorbing properties of biological tissue limit imaging depth to 1-2mm. Optical clearing agents have been utilized to increase imaging depth by index matching and lipid digestion, however, these contemporary techniques are expensive and harsh on tissues, often irreversibly denaturing proteins. Here we present an ideal optical clearing agent that offers ease-of-use and reversibility. Similar to how SeeDB has been effective for microscopy, our fructose-based, reversible optical clearing technique provides improved OCT imaging and functional immunohistochemical mapping of disease. Fructose is a natural, non-toxic sugar with excellent water solubility, capable of increasing tissue transparency and reducing light scattering. We will demonstrate the improved depth-resolving performance of OCT for enhanced whole-brain imaging of normal and diseased murine brains following a fructose clearing treatment. This technique potentially enables rapid, 3-dimensional evaluation of biological tissues at axial and lateral resolutions comparable to histopathology.

Evaluation of chlorpyrifos toxicity through a 28-day study: Cholinesterase activity, oxidative stress responses, parent compound/metabolite levels, and primary DNA damage in blood and brain tissue of adult male Wistar rats.

PubMed

Kopjar, Nevenka; Žunec, Suzana; Mendaš, Gordana; Micek, Vedran; Kašuba, Vilena; Mikolić, Anja; Lovaković, Blanka Tariba; Milić, Mirta; Pavičić, Ivan; Čermak, Ana Marija Marjanović; Pizent, Alica; Lucić Vrdoljak, Ana; Želježić, Davor

2018-01-05

In this 28 day-study, we evaluated the effects of the insecticide chlorpyrifos orally administered to Wistar rats at doses 0.160, 0.015, and 0.010 mg/kg b. w./day. Following treatment, total cholinesterase activity and activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were measured. Oxidative stress responses were evaluated using a battery of endpoints to establish lipid peroxidation, changes in total antioxidant capacity, level of reactive oxygen species (ROS), glutathione (GSH) level and activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase. Using HPLC-UV DAD analysis, levels of the parent compound and its main metabolite 3,5,6-trichloro-2-pyridinol in plasma and brain tissue were measured. The genotoxic effect was estimated using alkaline comet assay in leukocytes and brain tissue. The exposure did not result in significant effects on total cholinesterase, AChE and BChE activity in plasma and brain tissue. Lipid peroxidation slightly increased both in plasma and brain tissue. Total antioxidant capacity, ROS and GSH levels were marginally influenced by the exposure. Treatment led to significant increases of GSH-Px activity in blood, SOD activity in erythrocytes and a slight increase of catalase activity in plasma. HPLC-UV DAD analysis revealed the presence of both the parent compound and its main metabolite in the plasma of all of the experimental animals and brain tissue of the animals treated at the two higher doses. All of the tested doses of chlorpyrifos were slightly genotoxic, both to leukocytes and brain tissue. Our results call for further research using other sensitive biomarkers of effect, along with different exposure scenarios. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of solid-phase microextraction coupled with liquid chromatography for analysis of tramadol in brain tissue using its molecularly imprinted polymer.

PubMed

Habibi-Khorasani, Monireh; Mohammadpour, Amir Hooshang; Mohajeri, Seyed Ahmad

2017-02-01

In this work, performance of a molecularly imprinted polymer (MIP) as a selective solid-phase microextraction sorbent for the extraction and enrichment of tramadol in aqueous solution and rabbit brain tissue, is described. Binding properties of MIPs were studied in comparison with their nonimprinted polymer (NIP). Ten milligrams of the optimized MIP was then evaluated as a sorbent, for preconcentration, in molecularly imprinted solid-phase microextraction (MISPME) of tramadol from aqueous solution and rabbit brain tissue. The analytical method was calibrated in the range of 0.004 ppm (4 ng mL -1 ) and 10 ppm (10 μg mL -1 ) in aqueous media and in the ranges of 0.01 and 10 ppm in rabbit brain tissue, respectively. The results indicated significantly higher binding affinity of MIPs to tramadol, in comparison with NIP. The MISPME procedure was developed and optimized with a recovery of 81.12-107.54% in aqueous solution and 76.16-91.20% in rabbit brain tissue. The inter- and intra-day variation values were <8.24 and 5.06%, respectively. Finally the calibrated method was applied for determination of tramadol in real rabbit brain tissue samples after administration of a lethal dose. Our data demonstrated the potential of MISPME for rapid, sensitive and cost-effective sample analysis. Copyright © 2016 John Wiley & Sons, Ltd.

Tissue Probability Map Constrained 4-D Clustering Algorithm for Increased Accuracy and Robustness in Serial MR Brain Image Segmentation

PubMed Central

Xue, Zhong; Shen, Dinggang; Li, Hai; Wong, Stephen

2010-01-01

The traditional fuzzy clustering algorithm and its extensions have been successfully applied in medical image segmentation. However, because of the variability of tissues and anatomical structures, the clustering results might be biased by the tissue population and intensity differences. For example, clustering-based algorithms tend to over-segment white matter tissues of MR brain images. To solve this problem, we introduce a tissue probability map constrained clustering algorithm and apply it to serial MR brain image segmentation, i.e., a series of 3-D MR brain images of the same subject at different time points. Using the new serial image segmentation algorithm in the framework of the CLASSIC framework, which iteratively segments the images and estimates the longitudinal deformations, we improved both accuracy and robustness for serial image computing, and at the mean time produced longitudinally consistent segmentation and stable measures. In the algorithm, the tissue probability maps consist of both the population-based and subject-specific segmentation priors. Experimental study using both simulated longitudinal MR brain data and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data confirmed that using both priors more accurate and robust segmentation results can be obtained. The proposed algorithm can be applied in longitudinal follow up studies of MR brain imaging with subtle morphological changes for neurological disorders. PMID:26566399

Amplitude-integrated EEG in newborns with critical congenital heart disease predicts preoperative brain magnetic resonance imaging findings.

PubMed

Mulkey, Sarah B; Yap, Vivien L; Bai, Shasha; Ramakrishnaiah, Raghu H; Glasier, Charles M; Bornemeier, Renee A; Schmitz, Michael L; Bhutta, Adnan T

2015-06-01

The study aims are to evaluate cerebral background patterns using amplitude-integrated electroencephalography in newborns with critical congenital heart disease, determine if amplitude-integrated electroencephalography is predictive of preoperative brain injury, and assess the incidence of preoperative seizures. We hypothesize that amplitude-integrated electroencephalography will show abnormal background patterns in the early preoperative period in infants with congenital heart disease that have preoperative brain injury on magnetic resonance imaging. Twenty-four newborns with congenital heart disease requiring surgery at younger than 30 days of age were prospectively enrolled within the first 3 days of age at a tertiary care pediatric hospital. Infants had amplitude-integrated electroencephalography for 24 hours beginning close to birth and preoperative brain magnetic resonance imaging. The amplitude-integrated electroencephalographies were read to determine if the background pattern was normal, mildly abnormal, or severely abnormal. The presence of seizures and sleep-wake cycling were noted. The preoperative brain magnetic resonance imaging scans were used for brain injury and brain atrophy assessment. Fifteen of 24 infants had abnormal amplitude-integrated electroencephalography at 0.71 (0-2) (mean [range]) days of age. In five infants, the background pattern was severely abnormal. (burst suppression and/or continuous low voltage). Of the 15 infants with abnormal amplitude-integrated electroencephalography, 9 (60%) had brain injury. One infant with brain injury had a seizure on amplitude-integrated electroencephalography. A severely abnormal background pattern on amplitude-integrated electroencephalography was associated with brain atrophy (P = 0.03) and absent sleep-wake cycling (P = 0.022). Background cerebral activity is abnormal on amplitude-integrated electroencephalography following birth in newborns with congenital heart disease who have findings of brain injury and/or brain atrophy on preoperative brain magnetic resonance imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

Soft Tissue Phantoms for Realistic Needle Insertion: A Comparative Study.

PubMed

Leibinger, Alexander; Forte, Antonio E; Tan, Zhengchu; Oldfield, Matthew J; Beyrau, Frank; Dini, Daniele; Rodriguez Y Baena, Ferdinando

2016-08-01

Phantoms are common substitutes for soft tissues in biomechanical research and are usually tuned to match tissue properties using standard testing protocols at small strains. However, the response due to complex tool-tissue interactions can differ depending on the phantom and no comprehensive comparative study has been published to date, which could aid researchers to select suitable materials. In this work, gelatin, a common phantom in literature, and a composite hydrogel developed at Imperial College, were matched for mechanical stiffness to porcine brain, and the interactions during needle insertions within them were analyzed. Specifically, we examined insertion forces for brain and the phantoms; we also measured displacements and strains within the phantoms via a laser-based image correlation technique in combination with fluorescent beads. It is shown that the insertion forces for gelatin and brain agree closely, but that the composite hydrogel better mimics the viscous nature of soft tissue. Both materials match different characteristics of brain, but neither of them is a perfect substitute. Thus, when selecting a phantom material, both the soft tissue properties and the complex tool-tissue interactions arising during tissue manipulation should be taken into consideration. These conclusions are presented in tabular form to aid future selection.

High-contrast differentiation resolution 3D imaging of rodent brain by X-ray computed microtomography

NASA Astrophysics Data System (ADS)

Zikmund, T.; Novotná, M.; Kavková, M.; Tesařová, M.; Kaucká, M.; Szarowská, B.; Adameyko, I.; Hrubá, E.; Buchtová, M.; Dražanová, E.; Starčuk, Z.; Kaiser, J.

2018-02-01

The biomedically focused brain research is largely performed on laboratory mice considering a high homology between the human and mouse genomes. A brain has an intricate and highly complex geometrical structure that is hard to display and analyse using only 2D methods. Applying some fast and efficient methods of brain visualization in 3D will be crucial for the neurobiology in the future. A post-mortem analysis of experimental animals' brains usually involves techniques such as magnetic resonance and computed tomography. These techniques are employed to visualize abnormalities in the brains' morphology or reparation processes. The X-ray computed microtomography (micro CT) plays an important role in the 3D imaging of internal structures of a large variety of soft and hard tissues. This non-destructive technique is applied in biological studies because the lab-based CT devices enable to obtain a several-micrometer resolution. However, this technique is always used along with some visualization methods, which are based on the tissue staining and thus differentiate soft tissues in biological samples. Here, a modified chemical contrasting protocol of tissues for a micro CT usage is introduced as the best tool for ex vivo 3D imaging of a post-mortem mouse brain. This way, the micro CT provides a high spatial resolution of the brain microscopic anatomy together with a high tissue differentiation contrast enabling to identify more anatomical details in the brain. As the micro CT allows a consequent reconstruction of the brain structures into a coherent 3D model, some small morphological changes can be given into context of their mutual spatial relationships.

Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer's disease.

PubMed

Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J

2009-01-01

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy and environmental nuclear contamination as well as for Earth-orbit and space missions. Analyses of transcriptome profiles of mouse brain tissue after whole-body irradiation showed that low-dose exposures (10 cGy) induced genes not affected by high-dose radiation (2 Gy) and that low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues and pathways that were specific for brain tissue. Low-dose genes clustered into a saturated network (P < 10(-53)) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose irradiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down-regulated in normal human aging and Alzheimer's disease.

Time-dependent diffuse reflectance spectroscopy for in vivo characterization of pediatric epileptogenic brain lesions

NASA Astrophysics Data System (ADS)

Oh, Sanghoon; Ragheb, John; Bhatia, Sanjiv; Sandberg, David; Johnson, Mahlon; Fernald, Bradley; Lin, Wei-Chiang

2008-02-01

Optical spectroscopy for in vivo tissue diagnosis is performed traditionally in a static manner; a snap shot of the tissue biochemical and morphological characteristics is captured through the interaction between light and the tissue. This approach does not capture the dynamic nature of a living organ, which is critical to the studies of brain disorders such as epilepsy. Therefore, a time-dependent diffuse reflectance spectroscopy system with a fiber-optic probe was designed and developed. The system was designed to acquire broadband diffuse reflectance spectra (240 ~ 932 nm) at an acquisition rate of 33 Hz. The broadband spectral acquisition feature allows simultaneous monitoring of various physiological characteristics of tissues. The utility of such a system in guiding pediatric epilepsy surgery was tested in a pilot clinical study including 13 epilepsy patients and seven brain tumor patients. The control patients were children undergoing suregery for brain tumors in which measurements were taken from normal brain exposed during the surgery. Diffuse reflectance spectra were acquired for 12 seconds from various parts of the brain of the patients during surgery. Recorded spectra were processed and analyzed in both spectral and time domains to gain insights into the dynamic changes in, for example, hemodynamics of the investigated brain tissue. One finding from this pilot study is that unsynchronized alterations in local blood oxygenation and local blood volume were observed in epileptogenic cortex. These study results suggest the advantage of using a time-dependent diffuse reflectance spectroscopy system to study epileptogenic brain in vivo.

The meningeal lymphatic system: a route for HIV brain migration?

PubMed

Lamers, Susanna L; Rose, Rebecca; Ndhlovu, Lishomwa C; Nolan, David J; Salemi, Marco; Maidji, Ekaterina; Stoddart, Cheryl A; McGrath, Michael S

2016-06-01

Two innovative studies recently identified functional lymphatic structures in the meninges that may influence the development of HIV-associated neurological disorders (HAND). Until now, blood vessels were assumed to be the sole transport system by which HIV-infected monocytes entered the brain by bypassing a potentially hostile blood-brain barrier through inflammatory-mediated semi-permeability. A cascade of specific chemokine signals promote monocyte migration from blood vessels to surrounding brain tissues via a well-supported endothelium, where the cells differentiate into tissue macrophages capable of productive HIV infection. Lymphatic vessels on the other hand are more loosely organized than blood vessels. They absorb interstitial fluid from bodily tissues where HIV may persist and exchange a variety of immune cells (CD4(+) T cells, monocytes, macrophages, and dendritic cells) with surrounding tissues through discontinuous endothelial junctions. We propose that the newly discovered meningeal lymphatics are key to HIV migration among viral reservoirs and brain tissue during periods of undetectable plasma viral loads due to suppressive combinational antiretroviral therapy, thus redefining the migration process in terms of a blood-lymphatic transport system.

Optical imaging of cell death in traumatic brain injury using a heat shock protein-90 alkylator

PubMed Central

Xie, B-W; Park, D; Van Beek, E R; Blankevoort, V; Orabi, Y; Que, I; Kaijzel, E L; Chan, A; Hogg, P J; Löwik, C W G M

2013-01-01

Traumatic brain injury is a major public health concern and is characterised by both apoptotic and necrotic cell death in the lesion. Anatomical imaging is usually used to assess traumatic brain injuries and there is a need for imaging modalities that provide complementary cellular information. We sought to non-invasively image cell death in a mouse model of traumatic brain injury using a near-infrared fluorescent conjugate of a synthetic heat shock protein-90 alkylator, 4-(N-(S-glutathionylacetyl) amino) phenylarsonous acid (GSAO). GSAO labels both apoptotic and necrotic cells coincident with loss of plasma membrane integrity. The optical GSAO specifically labelled apoptotic and necrotic cells in culture and did not accumulate in healthy organs or tissues in the living mouse body. The conjugate is a very effective imager of cell death in brain lesions. The optical GSAO was detected by fluorescence intensity and GSAO bound to dying/dead cells was detected from prolongation of the fluorescence lifetime. An optimal signal-to-background ratio was achieved as early as 3 h after injection of the probe and the signal intensity positively correlated with both lesion size and probe concentration. This optical GSAO offers a convenient and robust means to non-invasively image apoptotic and necrotic cell death in brain and other lesions. PMID:23348587

[Neurological and technical aspects of deep brain stimulation].

PubMed

Voges, J; Krauss, J K

2010-06-01

Deep brain stimulation (DBS) is an important component of the therapy of movement disorders and has almost completely replaced high-frequency coagulation of brain tissue in stereotactic neurosurgery. Despite the functional efficacy of DBS, which in parts is documented on the highest evidence level, the underlying mechanisms are still not completely understood. According to the current state of knowledge electrophysiological and functional data give evidence that high-frequency DBS has an inhibitory effect around the stimulation electrode whilst at the same time axons entering or leaving the stimulated brain area are excited leading to modulation of neuronal networks. The latter effect modifies pathological discharges of neurons in key structures of the basal ganglia network (e.g. irregular bursting activity, oscillations or synchronization) which are found in particular movement disorders such as Parkinson' s disease or dystonia. The introduction of technical standards, such as the integration of high resolution MRI into computer-assisted treatment planning, in combination with special treatment planning software have contributed significantly to the reduction of severe surgical complications (frequency of intracranial hemorrhaging 1-3%) in recent years. Future developments will address the modification of hardware components of the stimulation system, the evaluation of new brain target areas, the simultaneous stimulation of different brain areas and the assessment of different stimulation paradigms (high-frequency vs low-frequency DBS).

Unilateral Opening of Rat Blood-Brain Barrier Assisted by Diagnostic Ultrasound Targeted Microbubbles Destruction.

PubMed

Xu, Yali; Cui, Hai; Zhu, Qiong; Hua, Xing; Xia, Hongmei; Tan, Kaibin; Gao, Yunhua; Zhao, Jing; Liu, Zheng

2016-01-01

Objective. Blood-brain barrier (BBB) is a key obstacle that prevents the medication from blood to the brain. Microbubble-enhanced cavitation by focused ultrasound can open the BBB and proves to be valuable in the brain drug delivery. The study aimed to explore the feasibility, efficacy, and safety of unilateral opening of BBB using diagnostic ultrasound targeted microbubbles destruction in rats. Methods. A transtemporal bone irradiation of diagnostic ultrasound and intravenous injection of lipid-coated microbubbles were performed at unilateral hemisphere. Pathological changes were monitored. Evans Blue extravasation grades, extraction from brain tissue, and fluorescence optical density were quantified. Lanthanum nitrate was traced by transmission electron microscopy. Results. After diagnostic ultrasound mediated microbubbles destruction, Evans Blue extravasation and fluorescence integrated optical density were significantly higher in the irradiated hemisphere than the contralateral side (all p < 0.01). Erythrocytes extravasations were demonstrated in the ultrasound-exposed hemisphere (4 ± 1, grade 2) while being invisible in the control side. Lanthanum nitrate tracers leaked through interendothelial cleft and spread to the nerve fiber existed in the irradiation side. Conclusions. Transtemporal bone irradiation under DUS mediated microbubble destruction provides us with a more accessible, safer, and higher selective BBB opening approach in rats, which is advantageous in brain targeted drugs delivery.

[Effects of mercazolyl and L-thyroxine on the antiedematous activity of immunotropic preparations during development of toxic brain edema and swelling].

PubMed

Platonov, I A; Anashchenkova, T A; Andreeva, T A

2008-01-01

Dysfunction of thyroid gland plays an important role in the pathogenesis of brain edema and swelling. Toxic brain edema and swelling was modeled under condition of hypo- and hyperfunction of thyroid gland. Mercazolyl and L-thyroxine ambiguously influence the development of toxic brain edema and swelling in rats. L-thyroxin (35.7 microg/kg) favors increase in the water content in brain tissue, which can be considered as synergism with the edematous factor and the formation of brain tissue susceptibility to the development of brain edema and swelling. The administration of mercazolyl (5 mg/kg) and L-thyroxin (35.7 microg/kg) with thymogen (10 microg/kg), thymalin (1.2 mg/kg), cycloferon (0.5 mg/kg) results in decreasing brain tissue density as compared to intact animals. Dysfunction of the thyroid gland leads to changes in pharmacodynamics of immune preparations, which results in a decrease of their antiedematous activity.

Alu sequence involvement in transcriptional insulation of the keratin 18 gene in transgenic mice.

PubMed Central

Thorey, I S; Ceceña, G; Reynolds, W; Oshima, R G

1993-01-01

The human keratin 18 (K18) gene is expressed in a variety of adult simple epithelial tissues, including liver, intestine, lung, and kidney, but is not normally found in skin, muscle, heart, spleen, or most of the brain. Transgenic animals derived from the cloned K18 gene express the transgene in appropriate tissues at levels directly proportional to the copy number and independently of the sites of integration. We have investigated in transgenic mice the dependence of K18 gene expression on the distal 5' and 3' flanking sequences and upon the RNA polymerase III promoter of an Alu repetitive DNA transcription unit immediately upstream of the K18 promoter. Integration site-independent expression of tandemly duplicated K18 transgenes requires the presence of either an 825-bp fragment of the 5' flanking sequence or the 3.5-kb 3' flanking sequence. Mutation of the RNA polymerase III promoter of the Alu element within the 825-bp fragment abolishes copy number-dependent expression in kidney but does not abolish integration site-independent expression when assayed in the absence of the 3' flanking sequence of the K18 gene. The characteristics of integration site-independent expression and copy number-dependent expression are separable. In addition, the formation of the chromatin state of the K18 gene, which likely restricts the tissue-specific expression of this gene, is not dependent upon the distal flanking sequences of the 10-kb K18 gene but rather may depend on internal regulatory regions of the gene. Images PMID:7692231

Using autopsy brain tissue to study alcohol-related brain damage in the genomic age.

PubMed

Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

2014-01-01

The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539). Copyright © 2013 by the Research Society on Alcoholism.

Using autopsy brain tissue to study alcohol-related brain damage in the genomic age

PubMed Central

Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

2013-01-01

The New South Wales Tissue Resource Centre (NSW TRC) at the University of Sydney, Australia is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain disease (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951–61) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539–52). PMID:24033426

Simultaneous measurement of brain tissue oxygen partial pressure, temperature, and global oxygen consumption during hibernation, arousal, and euthermy in non-sedated and non-anesthetized Arctic ground squirrels.

PubMed

Ma, Yilong; Wu, Shufen

2008-09-30

This study reports an online temperature correction method for determining tissue oxygen partial pressure P(tO2) in the striatum and a novel simultaneous measurement of brain P(tO2) and temperature (T(brain)) in conjunction with global oxygen consumption V(O2) in non-sedated and non-anesthetized freely moving Arctic ground squirrels (AGS, Spermophilus parryii). This method fills an important research gap-the lack of a suitable method for physiologic studies of tissue P(O2) in hibernating or other cool-blooded species. P(tO2) in AGS brain during euthermy (21.22+/-2.06 mmHg) is significantly higher (P=0.016) than during hibernation (13.21+/-0.46 mmHg) suggests brain oxygenation in the striatum is normoxic during euthermy and hypoxic during hibernation. These results in P(tO2) are different from blood oxygen partial pressure P(aO2) in AGS, which are significantly lower during euthermy than during hibernation and are actually hypoxic during euthermy and normoxic during hibernation in our previous study. This intriguing difference between the P(O2) of brain tissue and blood during these two physiological states suggests that regional mechanisms in the brain play a role in maintaining tissue oxygenation and protect against hypoxia during hibernation.

Utility of the Croatian translation of the community integration questionnaire-revised in a sample of adults with moderate to severe traumatic brain injury.

PubMed

Tršinski, Dubravko; Tadinac, Meri; Bakran, Žarko; Klepo, Ivana

2018-02-23

To examine the utility of the Community Integration Questionnaire-Revised, translated into Croatian, in a sample of adults with moderate to severe traumatic brain injury. The Community Integration Questionnaire-Revised was administered to a sample of 88 adults with traumatic brain injury and to a control sample matched by gender, age and education. Participants with traumatic brain injury were divided into four subgroups according to injury severity. The internal consistency of the Community Integration Questionnaire-Revised was satisfactory. The differences between the group with traumatic brain injury and the control group were statistically significant for the overall Community Integration Questionnaire-Revised score, as well as for all the subscales apart from the Home Integration subscale. The community Integration Questionnaire-Revised score varied significantly for subgroups with different severity of traumatic brain injury. The results show that the Croatian translation of the Community Integration Questionnaire-Revised is useful in assessing participation in adults with traumatic brain injury and confirm previous findings that severity of injury predicts community integration. Results of the new Electronic Social Networking scale indicate that persons who are more active on electronic social networks report better results for other domains of community integration, especially social activities. Implications for rehabilitation The Croatian translation of the Community Integration Questionnaire-Revised is a valid tool for long-term assessment of participation in various domains in persons with moderate to severe traumatic brain injury Persons with traumatic brain injury who are more active in the use of electronic social networking are also more integrated into social and productivity domains. Targeted training in the use of new technologies could enhance participation after traumatic brain injury.

Grey and white matter differences in brain energy metabolism in first episode schizophrenia: 31P-MRS chemical shift imaging at 4 Tesla.

PubMed

Jensen, J Eric; Miller, Jodi; Williamson, Peter C; Neufeld, Richard W J; Menon, Ravi S; Malla, Ashok; Manchanda, Rahul; Schaefer, Betsy; Densmore, Maria; Drost, Dick J

2006-03-31

Altered high energy and membrane metabolism, measured with phosphorus magnetic resonance spectroscopy (31P-MRS), has been inconsistently reported in schizophrenic patients in several anatomical brain regions implicated in the pathophysiology of this illness, with little attention to the effects of brain tissue type on the results. Tissue regression analysis correlates brain tissue type to measured metabolite levels, allowing for the extraction of "pure" estimated grey and white matter compartment metabolite levels. We use this tissue analysis technique on a clinical dataset of first episode schizophrenic patients and matched controls to investigate the effect of brain tissue specificity on altered energy and membrane metabolism. In vivo brain spectra from two regions, (a) the fronto-temporal-striatal region and (b) the frontal-lobes, were analyzed from 12 first episode schizophrenic patients and 11 matched controls from a (31)P chemical shift imaging (CSI) study at 4 Tesla (T) field strength. Tissue regression analyses using voxels from each region were performed relating metabolite levels to tissue content, examining phosphorus metabolite levels in grey and white matter compartments. Compared with controls, the first episode schizophrenic patient group showed significantly increased adenosine triphosphate levels (B-ATP) in white matter and decreased B-ATP levels in grey matter in the fronto-temporal-striatal region. No significant metabolite level differences were found in grey or white matter compartments in the frontal cortex. Tissue regression analysis reveals grey and white matter specific aberrations in high-energy phosphates in first episode schizophrenia. Although past studies report inconsistent regional differences in high-energy phosphate levels in schizophrenia, the present analysis suggests more widespread differences that seem to be strongly related to tissue type. Our data suggest that differences in grey and white matter tissue content between past studies may account for some of the variance in the literature.

[Alterations of glial fibrillary acidic protein in rat brain after gamma knife irradiation].

PubMed

Ma, Z M; Jiang, B; Ma, J R

2001-08-28

To study glial fibrillary acidic protein (GFAP) immunoreactivity in different time and water content of the rat brain treated with gamma knife radiotherapy and to understand the alteration course of the brain lesion after a single high dose radiosurgical treatment. In the brains of the normal rats were irradiated by gamma knife with 160 Gy-high dose. The irradiated rats were then killed on the 1st day, 7th day, 14th day, and 28th day after radiotherapy, respectively. The positive cells of GFAP in brain tissue were detected by immunostaining; the water content of the brain tissue was measured by microgravimetry. The histological study of the irradiated brain tissue was performed with H.E. and examined under light microscope. The numbers of GFAP-positive astrocytes began to increase on the 1st day after gamma knife irradiation. It was enlarged markedly in the number and size of GFAP-stained astrocytes over the irradiated areas. Up to the 28th day, circumscribed necrosis foci (4 mm in diameter) was seen in the central area of the target. In the brain tissue around the necrosis, GFAP-positive astrocytes significantly increased (P < 0.01, compared with the control group). The swelling of cells in irradiated region was observed on the 1st day; after irradiation endothelial cells degenerated and red blood cells escaped from blood vessel on the 7th day; leakage of Evans blue dye was observed in the target region on the 14th day. There was a significant decrease of specific gravity in the irradiated brain tissue the 14th and 28th day after irradiation. The results suggest that GFAP can be used as a marker for the radiation-induced brain injury. The brain edema and disruption of brain-blood barrier can be occurred during the acute stage after irradiation.

Selection of Reference Gene Expression in a Schizophrenia Brain Cohort

PubMed Central

Weickert, Cynthia Shannon; Sheedy, Donna; Rothmond, Debora A.; Dedova, Irina; Fung, Samantha; Garrick, Therese; Wong, Jenny; Harding, Antony J.; Sivagnanansundaram, Sinthuja; Hunt, Clare; Duncan, Carlotta; Sundqvist, Nina; Tsai, Shan-Yuan; Anand, Jasna; Draganic, Daren; Harper, Clive

2010-01-01

Objective To conduct postmortem human brain research into the neuropathological basis of schizophrenia, it is critical to establish cohorts that are well-characterised and well-matched. Our objective was to determine if specimen characteristics, including: diagnosis, age, postmortem interval (PMI), brain acidity (pH), and/or the agonal state of the subject at death related to RNA quality, and to determine the most appropriate reference gene mRNAs. Methods We selected a matched cohort of 74 cases (37 schizophrenia / schizoaffective disorder cases and 37 controls cases). Middle frontal gyrus tissue was pulverised, tissue pH was measured, RNA isolated for cDNA from each case, and RNA integrity number (RIN) measurements were assessed. Using RT-PCR, we measured nine housekeeper genes and calculated a geomean in each diagnostic group. Results We found that the RINs were very good (mean 7.3) and all nine housekeeper control genes were significantly correlated with RIN. Seven of nine housekeeper genes were also correlated with pH, and two clinical variables, agonal state and duration of illness did have an effect on some control mRNAs. No major impact of PMI or freezer time on housekeeper mRNAs was detected. Our results show that people with schizophrenia had significantly less PPIA, and SDHA and tended to have less GUSB and B2M mRNA suggesting that these control genes may not be good candidates for normalisation. Conclusions In our cohort, less than 10% variability in RIN values was detected and the diagnostic groups were well matched overall. Our cohort was adequately powered (0.80–0.90) to detect mRNA differences (25%) due to disease. Our study suggests that multiple factors should be considered in mRNA expression studies of human brain tissues. When schizophrenia cases are adequately matched to control cases subtle differences in gene expression can be reliably detected. PMID:20073568

Traffic pollution exposure is associated with altered brain connectivity in school children.

PubMed

Pujol, Jesus; Martínez-Vilavella, Gerard; Macià, Dídac; Fenoll, Raquel; Alvarez-Pedrerol, Mar; Rivas, Ioar; Forns, Joan; Blanco-Hinojo, Laura; Capellades, Jaume; Querol, Xavier; Deus, Joan; Sunyer, Jordi

2016-04-01

Children are more vulnerable to the effects of environmental elements due to their active developmental processes. Exposure to urban air pollution has been associated with poorer cognitive performance, which is thought to be a result of direct interference with brain maturation. We aimed to assess the extent of such potential effects of urban pollution on child brain maturation using general indicators of vehicle exhaust measured in the school environment and a comprehensive imaging evaluation. A group of 263 children, aged 8 to 12 years, underwent MRI to quantify regional brain volumes, tissue composition, myelination, cortical thickness, neural tract architecture, membrane metabolites, functional connectivity in major neural networks and activation/deactivation dynamics during a sensory task. A combined measurement of elemental carbon and NO2 was used as a putative marker of vehicle exhaust. Air pollution exposure was associated with brain changes of a functional nature, with no evident effect on brain anatomy, structure or membrane metabolites. Specifically, a higher content of pollutants was associated with lower functional integration and segregation in key brain networks relevant to both inner mental processes (the default mode network) and stimulus-driven mental operations. Age and performance (motor response speed) both showed the opposite effect to that of pollution, thus indicating that higher exposure is associated with slower brain maturation. In conclusion, urban air pollution appears to adversely affect brain maturation in a critical age with changes specifically concerning the functional domain. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of tissue optical properties on time-resolved fluorescence measurements from brain tumors: an experimental and computational study

NASA Astrophysics Data System (ADS)

Butte, Pramod V.; Vishwanath, Karthik; Pikul, Brian K.; Mycek, Mary-Ann; Marcu, Laura

2003-07-01

Time-Resolved Laser-Induced Fluorescence Spectroscopy (tr-LIFS) offers the potential for intra-operative diagnosis of primary brain tumors. However, both the intrinsic properties of endogenous fluorophores and the optical properties of brain tissue could affect the fluorescence measurements from brain. Scattering has been demonstrated to increase, for instance, detected lifetimes by 10-20% in media less scattering than the brain. The overall goal of this study is to investigate experimentally and computationally how optical properties of distinct types of brain tissue (normal porcine white and gray matter) affect the propagation of the excitation pulse and fluorescent transients and the detected fluorescence lifetime. A time-domain tr-LIFS apparatus (fast digitizer and gated detection) was employed to measure the propagation of ultra-short pulsed light through brain specimens (1-2.5-mm source-detector separation; 0.100-mm increment). A Monte Carlo model for semi-infinite turbid media was used to simulate time-resolved light propagation for arbitrary source-detector fiber geometries and optical fiber specifications; and to record spatially- and temporally resolved information. We determined a good correlation between experimental and computational results. Our findings provide means for quantification of time-resolved fluorescence spectra from healthy and diseased brain tissue.

Bioavailability and tissue distribution of Dechloranes in wild frogs (Rana limnocharis) from an e-waste recycling area in Southeast China.

PubMed

Li, Long; Wang, Wenyue; Lv, Quanxia; Ben, Yujie; Li, Xinghong

2014-03-01

Dechlorane Plus (DP), a flame retardant used as an alternative to decabromodiphenylether, has been frequently detected in organisms, indicating its bioaccumulation and biomagnification potential in aquatic and terrestrial species. However, little data is available on the bioaccumulation of DP in amphibians. Dechlorane Plus and its analogs (DPs) were detected in the liver, muscle and brain tissues of wild frogs (Rana limnocharis), which were collected from an e-waste recycling site, Southeast China. DP, Mirex, Dec 602 and a dechlorinated compound of DP (anti-Cl11-DP) varied in the range of 2.01-291, 0.650-179, 0.260-12.4, and not detected (nd)-8.67 ng/g lipid weight, respectively. No difference of tissue distribution was found for syn-DP, Mirex and Dec 602 between the liver and muscle tissue (liver/muscle concentration ratio close to 1, p > 0.05). However, higher retention was observed for anti-DP and anti-Cl11-DP in the frog muscle relative to the liver tissue (liver/muscle concentration ratio < 1, p < 0.05). Additionally, the blood-brain barrier was found to work efficiently to suppress these compounds entering brain tissues in this species (liver/brain concentration ratio > 1, p < 0.05), and the molecular weight was a key factor impacting the extent of the blood-brain barrier. Compared to levels in the muscle and brain tissue, a preferential enrichment of syn-DP was observed in the liver tissue, suggesting the occurrence of stereo-selective bioaccumulation in the wild frog. Copyright © 2014 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

PXR (NR1I2): splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators.

PubMed

Lamba, Vishal; Yasuda, Kazuto; Lamba, Jatinder K; Assem, Mahfoud; Davila, Julio; Strom, Stephen; Schuetz, Erin G

2004-09-15

To gain insight on the expression of pregnane X receptor (PXR), we analyzed PXR.1 and PXR alternatively spliced transcripts in a panel of 36 human tissues. PXR.1 was expressed in many more tissues than previously determined, including human bone marrow and select regions of the human brain. In each of these tissues, we observed alternative splicing of various exons of PXR that generated multiple distinct PXR isoforms. The most abundant PXR alternative mRNA transcripts lacked 111 nucleotides, deleting 37 amino acids from the PXR LBD (PXR.2), or lacked 123 nt, deleting 41 amino acids from the PXR LBD (PXR.3). CYP3A4, a gene transcriptionally regulated by PXR, showed incomplete overlap with PXR in its tissue distribution. Quantitation of PXR mRNAs in human liver demonstrated that PXR.2 and PXR.3 represented 6.7% and 0.32% of total PXR mRNA transcripts. Brain expression of PXR prompted analysis of whether some brain acting chemicals were PXR ligands. The neurosteroids allopregnanolone and pregnanolone activated PXR and induced transcription of a CYP3A4-luciferase reporter. Nicotine, the psychoactive and addictive chemical in cigarettes, and a known inducer of brain CYP2B6, was an efficacious activator of PXR and inducer of CYP3A4 transcription. Because nicotine activation of PXR will enhance metabolism of nicotine to the non-psychoactive cotinine, these results provide one molecular mechanism for the development of tolerance to nicotine. Moreover, the identification of PXR in many human tissues, such as brain, and activation by tissue specific ligands (such as neurosteroids) suggests additional biological roles for this receptor in these tissues.

A combination of experimental measurement, constitutive damage model, and diffusion tensor imaging to characterize the mechanical properties of the human brain.

PubMed

Karimi, Alireza; Rahmati, Seyed Mohammadali; Razaghi, Reza

2017-09-01

Understanding the mechanical properties of the human brain is deemed important as it may subject to various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the frontal lobe of the human brain. The constrained nonlinear minimization method was employed to identify the brain coefficients according to the axial and transversal compressive data. The pseudo-elastic damage model data was also well compared with that of the experimental data and it not only up to the primary loading but also the discontinuous softening could well address the mechanical behavior of the brain tissue.

Syringomyelia

MedlinePlus

... which brain tissue protrudes into your spinal canal (Chiari malformation). Other causes of syringomyelia include spinal cord tumors, ... protrusion of brain tissue into your spinal canal (Chiari malformation), symptoms generally may begin between ages 25 and ...

Regionally Impaired Redox Homeostasis in the Brain of Rats Subjected to Global Perinatal Asphyxia: Sustained Effect up to 14 Postnatal Days.

PubMed

Lespay-Rebolledo, Carolyne; Perez-Lobos, Ronald; Tapia-Bustos, Andrea; Vio, Valentina; Morales, Paola; Herrera-Marschitz, Mario

2018-06-29

The present report evaluates the effect of global perinatal asphyxia on several parameters of oxidative stress and cell viability in rat brain tissue sampled at an extended neonatal period up to 14 days, a period characterised by intensive neuritogenesis, synaptogenesis, synaptic consolidation, pruning and delayed cell death. Perinatal asphyxia was induced by immersing foetus-containing uterine horns removed by a caesarean section from on term rat dams into a water bath at 37 °C for 21 min. Asphyxia-exposed and sibling caesarean-delivered foetuses were manually resucitated and nurtured by surrogate dams for 1 to 14 postnatal (P) days. Brain samples (mesencephalon, telencephalon and hippocampus) were assayed for glutathione (reduced and oxidated levels; spectrophotometry), tissue reducing capacity (potassium ferricyanide reducing assay, FRAP), catalase (the key enzyme protecting against oxidative stress and reactive oxygen species, Western blots and ELISA) and cleaved caspase-3 (the key executioner of apoptosis, Western blots) levels. It was found that global PA produced a regionally specific and sustained increase in GSSG/GSH ratio, a regionally specific decrease in tissue reducing capacity and a regionally and time specific decrease of catalase activity and increase of cleaved caspase-3 levels. The present study provides evidence for regionally impaired redox homeostasis in the brain of rats subjected to global PA, an effect observed up to P14, mainly affecting mesencephalon and hippocampus, suggesting a sustained oxidative stress after the posthypoxia period. The oxidative stress observed postnatally can in part be associated to a respiratory apneic-like deficit, since there was a statistically significant decrease in respiration frequency in AS compared to CS neonates, also up to P14, together with the signs of a decreased peripheral blood perfusion (pink-blue skin colour in AS, compared to the pink colour observed in all CS neonates). It is proposed that PA implies a long-term metabolic insult, triggered by the length of hypoxia, the resuscitation/reoxigenation manoevres, but also by the developmental stage of the affected brain regions, and the integrity of cardiovascular and respiratory physiological functions, which are fundamental for warrantying a proper development.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Emin, David, E-mail: emin@unm.edu; Akhtari, Massoud; Ellingson, B. M.

We analyze the transient-dc and frequency-dependent electrical conductivities between blocking electrodes. We extend this analysis to measurements of ions’ transport in freshly excised bulk samples of human brain tissue whose complex cellular structure produces blockages. The associated ionic charge-carrier density and diffusivity are consistent with local values for sodium cations determined non-invasively in brain tissue by MRI (NMR) and diffusion-MRI (spin-echo NMR). The characteristic separation between blockages, about 450 microns, is very much shorter than that found for sodium-doped gel proxies for brain tissue, >1 cm.

Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1.

PubMed

Henninger, Nils; Bouley, James; Sikoglu, Elif M; An, Jiyan; Moore, Constance M; King, Jean A; Bowser, Robert; Freeman, Marc R; Brown, Robert H

2016-04-01

Axonal degeneration is a critical, early event in many acute and chronic neurological disorders. It has been consistently observed after traumatic brain injury, but whether axon degeneration is a driver of traumatic brain injury remains unclear. Molecular pathways underlying the pathology of traumatic brain injury have not been defined, and there is no efficacious treatment for traumatic brain injury. Here we show that mice lacking the mouse Toll receptor adaptor Sarm1 (sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) gene, a key mediator of Wallerian degeneration, demonstrate multiple improved traumatic brain injury-associated phenotypes after injury in a closed-head mild traumatic brain injury model. Sarm1(-/-) mice developed fewer β-amyloid precursor protein aggregates in axons of the corpus callosum after traumatic brain injury as compared to Sarm1(+/+) mice. Furthermore, mice lacking Sarm1 had reduced plasma concentrations of the phophorylated axonal neurofilament subunit H, indicating that axonal integrity is maintained after traumatic brain injury. Strikingly, whereas wild-type mice exibited a number of behavioural deficits after traumatic brain injury, we observed a strong, early preservation of neurological function in Sarm1(-/-) animals. Finally, using in vivo proton magnetic resonance spectroscopy we found tissue signatures consistent with substantially preserved neuronal energy metabolism in Sarm1(-/-) mice compared to controls immediately following traumatic brain injury. Our results indicate that the SARM1-mediated prodegenerative pathway promotes pathogenesis in traumatic brain injury and suggest that anti-SARM1 therapeutics are a viable approach for preserving neurological function after traumatic brain injury. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

POWER DENSITY, FIELD INTENSITY, AND CARRIER FREQUENCY DETERMINANTS OF RF-ENERGY-INDUCED CALCIUM-ION EFFLUX FROM BRAIN TISSUE

EPA Science Inventory

To explain a carrier frequency dependence reported for radiofrequency (RF)-induced calcium-ion efflux from brain tissue, a chick-brain hemisphere bathed in buffer solution is modeled as a sphere within the uniform field of the incident electromagnetic wave. Calculations on a sphe...

The Meninges: New Therapeutic Targets For Multiple Sclerosis

PubMed Central

Russi, Abigail E.; Brown, Melissa A.

2014-01-01

The CNS is largely comprised of non-regenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an “immune specialized” status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data has established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood barrier integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting of the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the blood brain barrier. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments. PMID:25241937

Optical imaging characterizing brain response to thermal insult in injured rodent

NASA Astrophysics Data System (ADS)

Abookasis, David; Shaul, Oren; Meitav, Omri; Pinhasi, Gadi A.

2018-02-01

We used spatially modulated optical imaging system to assess the effect of temperature elevation on intact brain tissue in a mouse heatstress model. Heatstress or heatstroke is a medical emergency defined by abnormally elevated body temperature that causes biochemical, physiological and hematological changes. During experiments, brain temperature was measured concurrently with a thermal camera while core body temperature was monitored with rectal thermocouple probe. Changes in a battery of macroscopic brain physiological parameters, such as hemoglobin oxygen saturation level, cerebral water content, as well as intrinsic tissue optical properties were monitored during temperature elevation. These concurrent changes reflect the pathophysiology of the brain during heatstress and demonstrate successful monitoring of thermoregulation mechanisms. In addition, the variation of tissue refractive index was calculated showing a monotonous decrease with increasing wavelength. We found increased temperature to greatly affect both the scattering properties and refractive index which represent cellular and subcellular swelling indicative of neuronal damage. The overall trends detected in brain tissue parameters were consistent with previous observations using conventional medical devices and optical modalities.

Fluorescence laminar optical tomography for brain imaging: system implementation and performance evaluation.

PubMed

Azimipour, Mehdi; Sheikhzadeh, Mahya; Baumgartner, Ryan; Cullen, Patrick K; Helmstetter, Fred J; Chang, Woo-Jin; Pashaie, Ramin

2017-01-01

We present our effort in implementing a fluorescence laminar optical tomography scanner which is specifically designed for noninvasive three-dimensional imaging of fluorescence proteins in the brains of small rodents. A laser beam, after passing through a cylindrical lens, scans the brain tissue from the surface while the emission signal is captured by the epi-fluorescence optics and is recorded using an electron multiplication CCD sensor. Image reconstruction algorithms are developed based on Monte Carlo simulation to model light–tissue interaction and generate the sensitivity matrices. To solve the inverse problem, we used the iterative simultaneous algebraic reconstruction technique. The performance of the developed system was evaluated by imaging microfabricated silicon microchannels embedded inside a substrate with optical properties close to the brain as a tissue phantom and ultimately by scanning brain tissue in vivo. Details of the hardware design and reconstruction algorithms are discussed and several experimental results are presented. The developed system can specifically facilitate neuroscience experiments where fluorescence imaging and molecular genetic methods are used to study the dynamics of the brain circuitries.

Proton MRS of the peritumoral brain.

PubMed

Chernov, Mikhail F; Kubo, Osami; Hayashi, Motohiro; Izawa, Masahiro; Maruyama, Takashi; Usukura, Masao; Ono, Yuko; Hori, Tomokatsu; Takakura, Kintomo

2005-02-15

Long-echo (TR: 2000 ms, TE: 136 ms) proton MRS of the cerebral tissue in the vicinity to intracranial lesion was done in 15 patients, mainly with parenchymal brain tumors. Significant decrease of N-acetylaspartate (NAA) (P<0.001) and more frequent presence of lactate (P<0.01) comparing with distant normal white matter were found in the perilesional brain tissue. The level of NAA in the perilesional brain tissue had negative associations with presence of lactate in the lesion (P<0.05), excess of lactate in the lesion compared to perilesional brain (P<0.01), grade of the perilesional edema (P<0.01) and patient's age (P<0.05). Multivariate analysis disclosed that identification of lactate in the lesion is associated with lower relative NAA content in the perilesional brain tissue, independently on the presence or absence of any other factor, including brain edema (P<0.001). In patients with lobar lesions who had at least one epileptic seizure during course of their disease the relative NAA content in the perilesional brain was significantly lower, comparing with those who were seizure-free (P<0.05). Therefore, lactate diffused from the tumor, or other metabolites secreted by lactate-producing neoplasm, should be considered as important contributors to the neuronal dysfunction in the surrounding brain. Decrease of NAA in the vicinity to intracranial lesions may reflect neuronal alteration responsible for associated epilepsy.

Ganoderma Lucidum Protects Rat Brain Tissue Against Trauma-Induced Oxidative Stress.

PubMed

Özevren, Hüseyin; İrtegün, Sevgi; Deveci, Engin; Aşır, Fırat; Pektanç, Gülsüm; Deveci, Şenay

2017-10-01

Traumatic brain injury causes tissue damage, breakdown of cerebral blood flow and metabolic regulation. This study aims to investigate the protective influence of antioxidant Ganoderma lucidum ( G. lucidum ) polysaccharides (GLPs) on brain injury in brain-traumatized rats. Sprague-Dawley conducted a head-traumatized method on rats by dropping off 300 g weight from 1 m height. Groups were categorized as control, G. lucidum , trauma, trauma+ G. lucidum (20 mL/kg per day via gastric gavage). Brain tissues were dissected from anesthetized rats 7 days after injury. For biochemical analysis, malondialdehyde, glutathione and myeloperoxidase values were measured. In histopathological examination, neuronal damage in brain cortex and changes in blood brain barrier were observed. In the analysis of immunohistochemical and western blot, p38 mitogen-activated protein kinase, vascular endothelial growth factor and cluster of differentiation 68 expression levels were shown. These analyzes demonstrated the beneficial effects of GLPs on brain injury. We propose that GLPs treatment after brain injury could be an alternative treatment to decraseing inflammation and edema, preventing neuronal and glial cells degeneration if given in appropriate dosage and in particular time intervals.

75 FR 76994 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-10

... Committee: Brain Disorders and Clinical Neuroscience Integrated Review Group Developmental Brain Disorders....gov . Name of Committee: Brain Disorders and Clinical Neuroscience Integrated Review Group, Cell [email protected] . Name of Committee: Brain Disorders and Clinical Neuroscience Integrated Review Group...

Evaluating Temperature Changes of Brain Tissue Due to Induced Heating of Cell Phone Waves.

PubMed

Forouharmajd, Farhad; Pourabdian, Siamak; Ebrahimi, Hossein

2018-01-01

Worries have recently been increased in the absorption of radiofrequency waves and their destructing effects on human health by increasing use of cell phones (mobile phones). This study performed to determine the thermal changes due to mobile phone radio frequency waves in gray and white brain tissue. This study is an empirical study, where the thermal changes of electromagnetic waves resulted from cell phones (900 MHZ, specific absorption rate for head 1.18 w/kg) on the 15 brain tissue of a cow were analyzed in a compartment with three different thickness of 2 mm, 12 mm, and 22 mm, for 15 min. The Lutron thermometer (model: MT-917) with 0.01°C precision was used for measuring the tissue temperature. For each thickness was measured three times. Data analysis is done by Lutron and MATLAB software packages. In confronting of the tissue with the cell phone, the temperature was increased by 0.53°C in the 2 mm thickness that is the gray matter of the brain, increased by 0.99°C in the 12 mm thickness, and also increased by 0.92°C in the 22 mm thickness. Brain temperature showed higher rates than the base temperature after 15 min of confrontation with cell phone waves in all the three thicknesses. Cell phone radiated radio frequency waves were effective on increasing brain tissue temperature, and this temperature increase has cumulative effect on the tissue, being higher, for some time after the confrontation than the time with no confrontation.

Evaluating Temperature Changes of Brain Tissue Due to Induced Heating of Cell Phone Waves

PubMed Central

Forouharmajd, Farhad; Pourabdian, Siamak; Ebrahimi, Hossein

2018-01-01

Background: Worries have recently been increased in the absorption of radiofrequency waves and their destructing effects on human health by increasing use of cell phones (mobile phones). This study performed to determine the thermal changes due to mobile phone radio frequency waves in gray and white brain tissue. Methods: This study is an empirical study, where the thermal changes of electromagnetic waves resulted from cell phones (900 MHZ, specific absorption rate for head 1.18 w/kg) on the 15 brain tissue of a cow were analyzed in a compartment with three different thickness of 2 mm, 12 mm, and 22 mm, for 15 min. The Lutron thermometer (model: MT-917) with 0.01°C precision was used for measuring the tissue temperature. For each thickness was measured three times. Data analysis is done by Lutron and MATLAB software packages. Results: In confronting of the tissue with the cell phone, the temperature was increased by 0.53°C in the 2 mm thickness that is the gray matter of the brain, increased by 0.99°C in the 12 mm thickness, and also increased by 0.92°C in the 22 mm thickness. Brain temperature showed higher rates than the base temperature after 15 min of confrontation with cell phone waves in all the three thicknesses. Conclusions: Cell phone radiated radio frequency waves were effective on increasing brain tissue temperature, and this temperature increase has cumulative effect on the tissue, being higher, for some time after the confrontation than the time with no confrontation. PMID:29861880

The sensitivity of normal brain and intracranially implanted VX2 tumour to interstitial photodynamic therapy.

PubMed Central

Lilge, L.; Olivo, M. C.; Schatz, S. W.; MaGuire, J. A.; Patterson, M. S.; Wilson, B. C.

1996-01-01

The applicability and limitations of a photodynamic threshold model, used to describe quantitatively the in vivo response of tissues to photodynamic therapy, are currently being investigated in a variety of normal and malignant tumour tissues. The model states that tissue necrosis occurs when the number of photons absorbed by the photosensitiser per unit tissue volume exceeds a threshold. New Zealand White rabbits were sensitised with porphyrin-based photosensitisers. Normal brain or intracranially implanted VX2 tumours were illuminated via an optical fibre placed into the tissue at craniotomy. The light fluence distribution in the tissue was measured by multiple interstitial optical fibre detectors. The tissue concentration of the photosensitiser was determined post mortem by absorption spectroscopy. The derived photodynamic threshold values for normal brain are significantly lower than for VX2 tumour for all photosensitisers examined. Neuronal damage is evident beyond the zone of frank necrosis. For Photofrin the threshold decreases with time delay between photosensitiser administration and light treatment. No significant difference in threshold is found between Photofrin and haematoporphyrin derivative. The threshold in normal brain (grey matter) is lowest for sensitisation by 5 delta-aminolaevulinic acid. The results confirm the very high sensitivity of normal brain to porphyrin photodynamic therapy and show the importance of in situ light fluence monitoring during photodynamic irradiation. Images Figure 1 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8562339

Aluminium in brain tissue in familial Alzheimer's disease.

PubMed

Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

2017-03-01

The genetic predispositions which describe a diagnosis of familial Alzheimer's disease can be considered as cornerstones of the amyloid cascade hypothesis. Essentially they place the expression and metabolism of the amyloid precursor protein as the main tenet of disease aetiology. However, we do not know the cause of Alzheimer's disease and environmental factors may yet be shown to contribute towards its onset and progression. One such environmental factor is human exposure to aluminium and aluminium has been shown to be present in brain tissue in sporadic Alzheimer's disease. We have made the first ever measurements of aluminium in brain tissue from 12 donors diagnosed with familial Alzheimer's disease. The concentrations of aluminium were extremely high, for example, there were values in excess of 10μg/g tissue dry wt. in 5 of the 12 individuals. Overall, the concentrations were higher than all previous measurements of brain aluminium except cases of known aluminium-induced encephalopathy. We have supported our quantitative analyses using a novel method of aluminium-selective fluorescence microscopy to visualise aluminium in all lobes of every brain investigated. The unique quantitative data and the stunning images of aluminium in familial Alzheimer's disease brain tissue raise the spectre of aluminium's role in this devastating disease. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

Effects of acupuncture on tissue-oxygenation of the rat brain.

PubMed

Chen, G S; Erdmann, W

1977-01-01

Acupuncture has been claimed to be effective in restoring consciousness in some comatose patients. Possible mechanisms to explain alleged acupuncture-induced arousal may include vasodilatory effects caused by sympathetic stimulation which leads to an augmentation of cerebral microcirculation and thereby improves oxygen supply to the brain tissue. Experiments were performed in ten albino rats (Wistar) employing PO2 microelectrodes which were inserted into the cortex of the animals through small burholes. Brain tissue PO2 was continuously recorded before, during, and after acupuncture. Stimulation of certain acupuncture loci (Go-26) resulted in immediate increase of PO2 in the frontal cortex of the rat brain. This effect was reproducible. The effect was comparable to that obtained with increase of inspiratory CO2 known to induce arterial vasodilatation and thus capillary perfusion pressure. The effect was more significant as compared to tissue PO2 increases obtained after increase of inspiratory oxygen concentration from 21% to 100%. It appears that acupuncture causes an increase of brain tissue perfusion which may be, at least in part, responsible for arousal of unconscious patients. Dilatation of cerebral vascular vessels and improvement of autoregulation in the brain by acupuncture stimulation may also explain the effectiveness of acupuncture in the treatment of migraine headache.

SU-E-T-587: Optimal Volumetric Modulated Arc Radiotherapy Treatment Planning Technique for Multiple Brain Metastases with Increasing Number of Arcs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keeling, V; Hossain, S; Hildebrand, K

Purpose: To show improvements in dose conformity and normal brain tissue sparing using an optimal planning technique (OPT) against clinically acceptable planning technique (CAP) in the treatment of multiple brain metastases. Methods: A standardized international benchmark case with12 intracranial tumors was planned using two different VMAT optimization methods. Plans were split into four groups with 3, 6, 9, and 12 targets each planned with 3, 5, and 7 arcs using Eclipse TPS. The beam geometries were 1 full coplanar and half non-coplanar arcs. A prescription dose of 20Gy was used for all targets. The following optimization criteria was used (OPTmore » vs. CAP): (No upper limit vs.108% upper limit for target volume), (priority 140–150 vs. 75–85 for normal-brain-tissue), and (selection of automatic sparing Normal-Tissue-Objective (NTO) vs. Manual NTO). Both had priority 50 to critical structures such as brainstem and optic-chiasm, and both had an NTO priority 150. Normal-brain-tissue doses along with Paddick Conformity Index (PCI) were evaluated. Results: In all cases PCI was higher for OPT plans. The average PCI (OPT,CAP) for all targets was (0.81,0.64), (0.81,0.63), (0.79,0.57), and (0.72,0.55) for 3, 6, 9, and 12 target plans respectively. The percent decrease in normal brain tissue volume (OPT/CAP*100) achieved by OPT plans was (reported as follows: V4, V8, V12, V16, V20) (184, 343, 350, 294, 371%), (192, 417, 380, 299, 360%), and (235, 390, 299, 281, 502%) for the 3, 5, 7 arc 12 target plans, respectively. The maximum brainstem dose decreased for the OPT plan by 4.93, 4.89, and 5.30 Gy for 3, 5, 7 arc 12 target plans, respectively. Conclusion: Substantial increases in PCI, critical structure sparing, and decreases in normal brain tissue dose were achieved by eliminating upper limits from optimization, using automatic sparing of normal tissue function with high priority, and a high priority to normal brain tissue.« less

Protection of cortex by overlying meninges tissue during dynamic indentation of the adolescent brain.

PubMed

MacManus, David B; Pierrat, Baptiste; Murphy, Jeremiah G; Gilchrist, Michael D

2017-07-15

Traumatic brain injury (TBI) has become a recent focus of biomedical research with a growing international effort targeting material characterization of brain tissue and simulations of trauma using computer models of the head and brain to try to elucidate the mechanisms and pathogenesis of TBI. The meninges, a collagenous protective tri-layer, which encloses the entire brain and spinal cord has been largely overlooked in these material characterization studies. This has resulted in a lack of accurate constitutive data for the cranial meninges, particularly under dynamic conditions such as those experienced during head impacts. The work presented here addresses this lack of data by providing for the first time, in situ large deformation material properties of the porcine dura-arachnoid mater composite under dynamic indentation. It is demonstrated that this tissue is substantially stiffer (shear modulus, μ=19.10±8.55kPa) and relaxes at a slower rate (τ 1 =0.034±0.008s, τ 2 =0.336±0.077s) than the underlying brain tissue (μ=6.97±2.26kPa, τ 1 =0.021±0.007s, τ 2 =0.199±0.036s), reducing the magnitudes of stress by 250% and 65% for strains that arise during indentation-type deformations in adolescent brains. We present the first mechanical analysis of the protective capacity of the cranial meninges using in situ micro-indentation techniques. Force-relaxation tests are performed on in situ meninges and cortex tissue, under large strain dynamic micro-indentation. A quasi-linear viscoelastic model is used subsequently, providing time-dependent mechanical properties of these neural tissues under loading conditions comparable to what is experienced in TBI. The reported data highlights the large differences in mechanical properties between these two tissues. Finite element simulations of the indentation experiments are also performed to investigate the protective capacity of the meninges. These simulations show that the meninges protect the underlying brain tissue by reducing the overall magnitude of stress by 250% and up to 65% for strains. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Reference genes for reverse transcription quantitative PCR in canine brain tissue.

PubMed

Stassen, Quirine E M; Riemers, Frank M; Reijmerink, Hannah; Leegwater, Peter A J; Penning, Louis C

2015-12-09

In the last decade canine models have been used extensively to study genetic causes of neurological disorders such as epilepsy and Alzheimer's disease and unravel their pathophysiological pathways. Reverse transcription quantitative polymerase chain reaction is a sensitive and inexpensive method to study expression levels of genes involved in disease processes. Accurate normalisation with stably expressed so-called reference genes is crucial for reliable expression analysis. Following the minimum information for publication of quantitative real-time PCR experiments precise guidelines, the expression of ten frequently used reference genes, namely YWHAZ, HMBS, B2M, SDHA, GAPDH, HPRT, RPL13A, RPS5, RPS19 and GUSB was evaluated in seven brain regions (frontal lobe, parietal lobe, occipital lobe, temporal lobe, thalamus, hippocampus and cerebellum) and whole brain of healthy dogs. The stability of expression varied between different brain areas. Using the GeNorm and Normfinder software HMBS, GAPDH and HPRT were the most reliable reference genes for whole brain. Furthermore based on GeNorm calculations it was concluded that as little as two to three reference genes are sufficient to obtain reliable normalisation, irrespective the brain area. Our results amend/extend the limited previously published data on canine brain reference genes. Despite the excellent expression stability of HMBS, GAPDH and HRPT, the evaluation of expression stability of reference genes must be a standard and integral part of experimental design and subsequent data analysis.

Re-emergence of modular brain networks in stroke recovery.

PubMed

Siegel, Joshua S; Seitzman, Benjamin A; Ramsey, Lenny E; Ortega, Mario; Gordon, Evan M; Dosenbach, Nico U F; Petersen, Steven E; Shulman, Gordon L; Corbetta, Maurizio

2018-04-01

Studies of stroke have identified local reorganization in perilesional tissue. However, because the brain is highly networked, strokes also broadly alter the brain's global network organization. Here, we assess brain network structure longitudinally in adult stroke patients using resting state fMRI. The topology and boundaries of cortical regions remain grossly unchanged across recovery. In contrast, the modularity of brain systems i.e. the degree of integration within and segregation between networks, was significantly reduced sub-acutely (n = 107), but partially recovered by 3 months (n = 85), and 1 year (n = 67). Importantly, network recovery correlated with recovery from language, spatial memory, and attention deficits, but not motor or visual deficits. Finally, in-depth single subject analyses were conducted using tools for visualization of changes in brain networks over time. This exploration indicated that changes in modularity during successful recovery reflect specific alterations in the relationships between different networks. For example, in a patient with left temporo-parietal stroke and severe aphasia, sub-acute loss of modularity reflected loss of association between frontal and temporo-parietal regions bi-hemispherically across multiple modules. These long-distance connections then returned over time, paralleling aphasia recovery. This work establishes the potential importance of normalization of large-scale modular brain systems in stroke recovery. Copyright © 2017. Published by Elsevier Ltd.

String Vessel Formation is Increased in the Brain of Parkinson Disease.

PubMed

Yang, Panzao; Pavlovic, Darja; Waldvogel, Henry; Dragunow, Mike; Synek, Beth; Turner, Clinton; Faull, Richard; Guan, Jian

2015-01-01

String vessels are collapsed basement membrane without endothelium and have no function in circulation. String vessel formation contributes to vascular degeneration in Alzheimer disease. By comparing to age-matched control cases we have recently reported endothelial degeneration in brain capillaries of human Parkinson disease (PD). Current study evaluated changes of basement membrane of capillaries, string vessel formation and their association with astrocytes, blood-brain-barrier integrity and neuronal degeneration in PD. Brain tissue from human cases of PD and age-matched controls was used. Immunohistochemical staining for collagen IV, GFAP, NeuN, tyrosine hydroxylase, fibrinogen and Factor VIII was evaluated by image analysis in the substantia nigra, caudate nucleus and middle frontal gyrus. While the basement-membrane-associated vessel density was similar between the two groups, the density of string vessels was significantly increased in the PD cases, particularly in the substantia nigra. Neuronal degeneration was found in all brain regions. Astrocytes and fibrinogen were increased in the caudate nuclei of PD cases compared with control cases. Endothelial degeneration and preservation of basement membrane result in an increase of string vessel formation in PD. The data may suggest a possible role for cerebral hypoperfusion in the neuronal degeneration characteristic of PD, which needs further investigation. Elevated astrocytosis in the caudate nucleus of PD cases could be associated with disruption of the blood-brain barrier in this brain region.

Chlorella diet alters mitochondrial cardiolipin contents differentially in organs of Danio rerio analyzed by a lipidomics approach

PubMed Central

Chao, Yu-Jen; Wu, Wen-Hsin; Balazova, Maria; Wu, Ting-Yuan; Lin, Jamie; Liu, Yi-Wen

2018-01-01

The zebrafish (Danio rerio) is an important and widely used vertebrate model organism for the study of human diseases which include disorders caused by dysfunctional mitochondria. Mitochondria play an essential role in both energy metabolism and apoptosis, which are mediated through a mitochondrial phospholipid cardiolipin (CL). In order to examine the cardiolipin profile in the zebrafish model, we developed a CL analysis platform by using liquid chromatography-mass spectrometry (LC-MS). Meanwhile, we tested whether chlorella diet would alter the CL profile in the larval fish, and in various organs of the adult fish. The results showed that chlorella diet increased the chain length of CL in larval fish. In the adult zebrafish, the distribution patterns of CL species were similar between the adult brain and eye tissues, and between the heart and muscles. Interestingly, monolyso-cardiolipin (MLCL) was not detected in brain and eyes but found in other examined tissues, indicating a different remodeling mechanism to maintain the CL integrity. While the adult zebrafish were fed with chlorella for four weeks, the CL distribution showed an increase of the species of saturated acyl chains in the brain and eyes, but a decrease in the other organs. Moreover, chlorella diet led to a decrease of MLCL percentage in organs except the non-MLCL-containing brain and eyes. The CL analysis in the zebrafish provides an important tool for studying the mechanism of mitochondria diseases, and may also be useful for testing medical regimens targeting against the Barth Syndrome. PMID:29494608

Brain herniation

MedlinePlus

... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hou, P; Park, P; Li, H

Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated withmore » PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.« less

Neurodegenerative dementias: From MR Physics lab to assessment room

NASA Astrophysics Data System (ADS)

Bruno, S. D.; Cercignani, M.; Wheeler-Kingshott, C. A. M.

2012-11-01

Theimpact of neuroimaging on the study and understanding of dementing illnesses has been enormous. Here we review the main MR structural technical developments applied to Alzheimer's disease and fronto-temporal dementia, two forms of neurodegenerative disorders that have a number of similarities but also several differences. The possibility of detecting increasingly subtle brain changes, together with the need of handling larger and larger data sets, keeping up with the ever expanding aging population, are perhaps the main driving forces behind recent MR technique developments in the field of dementia. The measurement of atrophy is now integrated by more advanced approaches, investigating the alterations of the architecture of brain tissues beyond pure volumetric loss. Brain connectivity is now studied in vivo with techniques such as diffusion tensor imaging and tractography. Also, automated methods of subject classification open up new possibilities of rapid and cost-effective diagnosis. The inter-disciplinary efforts are changing the clinical scenario of dementia care from one of helpless defeat to one of promising innovation.

Proteomic approaches in brain research and neuropharmacology.

PubMed

Vercauteren, Freya G G; Bergeron, John J M; Vandesande, Frans; Arckens, Lut; Quirion, Rémi

2004-10-01

Numerous applications of genomic technologies have enabled the assembly of unprecedented inventories of genes, expressed in cells under specific physiological and pathophysiological conditions. Complementing the valuable information generated through functional genomics with the integrative knowledge of protein expression and function should enable the development of more efficient diagnostic tools and therapeutic agents. Proteomic analyses are particularly suitable to elucidate posttranslational modifications, expression levels and protein-protein interactions of thousands of proteins at a time. In this review, two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) investigations of brain tissues in neurodegenerative diseases such as Alzheimer's disease, Down syndrome and schizophrenia, and the construction of 2D-PAGE proteome maps of the brain are discussed. The role of the Human Proteome Organization (HUPO) as an international coordinating organization for proteomic efforts, as well as challenges for proteomic technologies and data analysis are also addressed. It is expected that the use of proteomic strategies will have significant impact in neuropharmacology over the coming decade.

Effect of dietary docosahexaenoic acid (DHA) in phospholipids or triglycerides on brain DHA uptake and accretion.

PubMed

Kitson, Alex P; Metherel, Adam H; Chen, Chuck T; Domenichiello, Anthony F; Trépanier, Marc-Olivier; Berger, Alvin; Bazinet, Richard P

2016-07-01

Tracer studies suggest that phospholipid DHA (PL-DHA) more effectively targets the brain than triglyceride DHA (TAG-DHA), although the mechanism and whether this translates into higher brain DHA concentrations are not clear. Rats were gavaged with [U-(3)H]PL-DHA and [U-(3)H]TAG-DHA and blood sampled over 6h prior to collection of brain regions and other tissues. In another experiment, rats were supplemented for 4weeks with TAG-DHA (fish oil), PL-DHA (roe PL) or a mixture of both for comparison to a low-omega-3 diet. Brain regions and other tissues were collected, and blood was sampled weekly. DHA accretion rates were estimated using the balance method. [U-(3)H]PL-DHA rats had higher radioactivity in cerebellum, hippocampus and remainder of brain, with no differences in other tissues despite higher serum lipid radioactivity in [U-(3)H]TAG-DHA rats. TAG-DHA, PL-DHA or a mixture were equally effective at increasing brain DHA. There were no differences between DHA-supplemented groups in brain region, whole-body, or tissue DHA accretion rates except heart and serum TAG where the PL-DHA/TAG-DHA blend was higher than TAG-DHA. Apparent DHA β-oxidation was not different between DHA-supplemented groups. This indicates that more labeled DHA enters the brain when consumed as PL; however, this may not translate into higher brain DHA concentrations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The Effects of Changing Water Content, Relaxation Times, and Tissue Contrast on Tissue Segmentation and Measures of Cortical Anatomy in MR Images

PubMed Central

Bansal, Ravi; Hao, Xuejun; Liu, Feng; Xu, Dongrong; Liu, Jun; Peterson, Bradley S.

2013-01-01

Water content is the dominant chemical compound in the brain and it is the primary determinant of tissue contrast in magnetic resonance (MR) images. Water content varies greatly between individuals, and it changes dramatically over time from birth through senescence of the human life span. We hypothesize that the effects that individual- and age-related variations in water content have on contrast of the brain in MR images also has important, systematic effects on in vivo, MRI-based measures of regional brain volumes. We also hypothesize that changes in water content and tissue contrast across time may account for age-related changes in regional volumes, and that differences in water content or tissue contrast across differing neuropsychiatric diagnoses may account for differences in regional volumes across diagnostic groups. We demonstrate in several complementary ways that subtle variations in water content across age and tissue compartments alter tissue contrast, and that changing tissue contrast in turn alters measures of the thickness and volume of the cortical mantle: (1) We derive analytic relations describing how age-related changes in tissue relaxation times produce age-related changes in tissue gray-scale intensity values and tissue contrast; (2) We vary tissue contrast in computer-generated images to assess its effects on tissue segmentation and volumes of gray matter and white matter; and (3) We use real-world imaging data from adults with either Schizophrenia or Bipolar Disorder and age- and sex-matched healthy adults to assess the ways in which variations in tissue contrast across diagnoses affects group differences in tissue segmentation and associated volumes. We conclude that in vivo MRI-based morphological measures of the brain, including regional volumes and measures of cortical thickness, are a product of, or at least are confounded by, differences in tissue contrast across individuals, ages, and diagnostic groups, and that differences in tissue contrast in turn likely derive from corresponding differences in water content of the brain across individuals, ages, and diagnostic groups. PMID:24055410

Clinical efficacy of positron emission tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heiss, W.D.; Pawlick, G.; Herholz, K.

1987-01-01

The contents of this book are: Brain: Cerebral Vascular Disease; Brain: Movement Disorders; Brain: Epilepsy and Pediatric Neurology; Brain: Dementias; Brain: Schizophrenia; Heart: Angina Pectoris; Heart: Infarction; Lungs; Soft Tissue Tumors; and Brain Tumors.

Over-hydration detection in brain by magnetic induction spectroscopy

NASA Astrophysics Data System (ADS)

González, César A.; Pérez, María; Hevia, Nidiyare; Arámbula, Fernándo; Flores, Omar; Aguilar, Eliot; Hinojosa, Ivonne; Joskowicz, Leo; Rubinsky, Boris

2010-04-01

Detection and continuous monitoring of edema in the brain in early stages is useful for assessment of medical condition and treatment. We have proposed a solution in which the bulk measurements of the tissue electrical properties to detect edema or in general accumulation of fluids are made through measurement of the magnetic induction phase shift between applied and measured currents at different frequencies (Magnetic Induction Spectroscopy; MIS). Magnetic Resonant Imaging (MRI) has been characterized because its capability to detect different levels of brain tissue hydration by differences in diffusion-weighted (DW) sequences and it's involve apparent diffusion coefficient (ADC). The objective of this study was to explore the viability to use measurements of the bulk tissue electrical properties to detect edema or in general accumulation of fluids by MIS. We have induced a transitory and generalized tissue over-hydration condition in ten volunteers ingesting 1.5 to 2 liters of water in ten minutes. Basal and over-hydration conditions were monitored by MIS and MRI. Changes in the inductive phase shift at certain frequencies were consistent with changes in the brain tissue hydration level observed by DW-ADC. The results suggest that MIS has the potential to detect pathologies associated to changes in the content of fluids in brain tissue such as edema and hematomas.

Integrin suppresses neurogenesis and regulates brain tissue assembly in planarian regeneration.

PubMed

Bonar, Nicolle A; Petersen, Christian P

2017-03-01

Animals capable of adult regeneration require specific signaling to control injury-induced cell proliferation, specification and patterning, but comparatively little is known about how the regeneration blastema assembles differentiating cells into well-structured functional tissues. Using the planarian Schmidtea mediterranea as a model, we identify β1-integrin as a crucial regulator of blastema architecture. β1-integrin(RNAi) animals formed small head blastemas with severe tissue disorganization, including ectopic neural spheroids containing differentiated neurons normally found in distinct organs. By mimicking aspects of normal brain architecture but without normal cell-type regionalization, these spheroids bore a resemblance to mammalian tissue organoids synthesized in vitro We identified one of four planarian integrin-alpha subunits inhibition of which phenocopied these effects, suggesting that a specific receptor controls brain organization through regeneration. Neoblast stem cells and progenitor cells were mislocalized in β1-integrin(RNAi) animals without significantly altered body-wide patterning. Furthermore, tissue disorganization phenotypes were most pronounced in animals undergoing brain regeneration and not homeostatic maintenance or regeneration-induced remodeling of the brain. These results suggest that integrin signaling ensures proper progenitor recruitment after injury, enabling the generation of large-scale tissue organization within the regeneration blastema. © 2017. Published by The Company of Biologists Ltd.

Extracting morphologies from third harmonic generation images of structurally normal human brain tissue.

PubMed

Zhang, Zhiqing; Kuzmin, Nikolay V; Groot, Marie Louise; de Munck, Jan C

2017-06-01

The morphologies contained in 3D third harmonic generation (THG) images of human brain tissue can report on the pathological state of the tissue. However, the complexity of THG brain images makes the usage of modern image processing tools, especially those of image filtering, segmentation and validation, to extract this information challenging. We developed a salient edge-enhancing model of anisotropic diffusion for image filtering, based on higher order statistics. We split the intrinsic 3-phase segmentation problem into two 2-phase segmentation problems, each of which we solved with a dedicated model, active contour weighted by prior extreme. We applied the novel proposed algorithms to THG images of structurally normal ex-vivo human brain tissue, revealing key tissue components-brain cells, microvessels and neuropil, enabling statistical characterization of these components. Comprehensive comparison to manually delineated ground truth validated the proposed algorithms. Quantitative comparison to second harmonic generation/auto-fluorescence images, acquired simultaneously from the same tissue area, confirmed the correctness of the main THG features detected. The software and test datasets are available from the authors. z.zhang@vu.nl. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Multimodality stereotactic brain tissue identification: the NASA smart probe project

NASA Technical Reports Server (NTRS)

Andrews, R.; Mah, R.; Aghevli, A.; Freitas, K.; Galvagni, A.; Guerrero, M.; Papsin, R.; Reed, C.; Stassinopoulos, D.

1999-01-01

Real-time tissue identification can benefit procedures such as stereotactic brain biopsy, functional neurosurgery and brain tumor excision. Optical scattering spectroscopy has been shown to be effective at discriminating cancer from noncancerous conditions in the colon, bladder and breast. The NASA Smart Probe extends the concept of 'optical biopsy' by using neural network techniques to combine the output from 3 microsensors contained within a cannula 2. 7 mm in diameter (i.e. the diameter of a stereotactic brain biopsy needle). Experimental data from 5 rats show the clear differentiation between tissues such as brain, nerve, fat, artery and muscle that can be achieved with optical scattering spectroscopy alone. These data and previous findings with other modalities such as (1) analysis of the image from a fiberoptic neuroendoscope and (2) the output from a microstrain gauge suggest the Smart Probe multiple microsensor technique shows promise for real-time tissue identification in neurosurgical procedures. Copyright 2000 S. Karger AG, Basel.

Adoptive transfer of T regulatory cells inhibits lipopolysaccharide-induced inflammation in fetal brain tissue in a late-pregnancy preterm birth mouse model.

PubMed

Wang, Fan; Xiao, Mi; Chen, Ru-Juan; Lin, Xiao-Jie; Siddiq, Muhammad; Liu, Li

2017-02-01

To evaluate the effect of regulatory T cells (Tregs) on the inflammation resulting from lipopolysaccharide (LPS) challenge in prenatal brain tissue, Tregs isolated from pregnant mice were transferred into model mice, and the expression levels of fork head family transcription factor (Foxp3), interleukin-6 (IL-6), CD68 (a marker of microglia), and toll-like receptor 4 (TLR-4) were assessed in the fetal brain tissue. Foxp3, IL-6, and TLR-4 expression were detected by polymerase chain reaction and Western blot; CD68 expression level was detected using immunochemical analysis. Foxp3, IL-6, TLR-4, and CD68 expressions in fetal brain were significantly induced by maternal LPS administration, and the increased expression levels were markedly reduced by adoptive transfer of Tregs. Maternal LPS exposure significantly induced inflammation in perinatal brain tissue, and Tregs negatively regulated this LPS-induced inflammation. © 2016 International Federation for Cell Biology.

Delivery of Nano-Tethered Therapies to Brain Metastases of Primary Breast Cancer Using a Cellular Trojan Horse

DTIC Science & Technology

2015-10-01

tomography images. The CT image densities in Hounsfield units (HU) of the brain were translated into corresponding optical properties (absorption...derived the Hounsfield units and optical properties of brain tissues such as white/gray matter. 13-15 The segmentation software generated an optical map...treatment protocol. Head CT image densities (in Hounsfield Units /HU) are segmented and translated into optical properties of the brain tissue

Enzymatic Digestion of Eye and Brain Tissues of Sockeye and Coho Salmon, and Dusky Rockfish Commercially Harvested in Alaska

USDA-ARS?s Scientific Manuscript database

Potential feed ingredients with high lipid content were made by enzymatic digestion followed by centrifugation of eye tissue from dusky rockfish (Sebastes ciliatos), coho salmon (Oncorhynchus kisutch), and sockeye salmon (Oncorhynchus nerka) and brain tissue from sockeye salmon. Materials with high ...

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use

PubMed Central

2013-01-01

Background A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Methods/Design Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. Discussion We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding variable of early adolescent onset of regular cannabis use. PMID:24131511

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use.

PubMed

Bernier, Denise; Cookey, Jacob; McAllindon, David; Bartha, Robert; Hanstock, Christopher C; Newman, Aaron J; Stewart, Sherry H; Tibbo, Philip G

2013-10-17

A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding variable of early adolescent onset of regular cannabis use.

Use of a rapid brain-sampling technique in a physiologic preparation: effects of morphine, ketamine, and halothane on tissue energy intermediates.

PubMed

Dedrick, D F; Sherer, Y D; Biebuyck, J F

1975-06-01

A new method of rapid sampling of brain tissue, "freeze-blowing," has been used to compare the neurochemistry of the brain during anesthesia with that in the awake state. The method avoids anoxia associated with the sampling process. Physiologic variables, including body temperature, blood-gas tensions and blood pressure, were carefully monitored and controlled in the experimental animals. None of the agents tested (halothane, morphine, and ketamine) reduced the brain tissue high-energy phosphate reserved. All three drugs doubled glucose levels. Morphine lowered both lactate and the lactate/pyruvate ratio. Uniformly, the three anesthetic agents led to twofold increases of brain cyclic 3'-5' adenosine monophosphate concentrations. These changes suggest a possible role for cyclic nucleotides in central neurotransmission.

Spectroscopic magnetic resonance imaging of the brain: voxel localisation and tissue segmentation in the follow up of brain tumour.

PubMed

Poloni, Guy; Bastianello, S; Vultaggio, Angela; Pozzi, S; Maccabelli, Gloria; Germani, Giancarlo; Chiarati, Patrizia; Pichiecchio, Anna

2008-01-01

The field of application of magnetic resonance spectroscopy (MRS) in biomedical research is expanding all the time and providing opportunities to investigate tissue metabolism and function. The data derived can be integrated with the information on tissue structure gained from conventional and non-conventional magnetic resonance imaging (MRI) techniques. Clinical MRS is also strongly expected to play an important role as a diagnostic tool. Essential for the future success of MRS as a clinical and research tool in biomedical sciences, both in vivo and in vitro, is the development of an accurate, biochemically relevant and physically consistent and reliable data analysis standard. Stable and well established analysis algorithms, in both the time and the frequency domain, are already available, as is free commercial software for implementing them. In this study, we propose an automatic algorithm that takes into account anatomical localisation, relative concentrations of white matter, grey matter, cerebrospinal fluid and signal abnormalities and inter-scan patient movement. The endpoint is the collection of a series of covariates that could be implemented in a multivariate analysis of covariance (MANCOVA) of the MRS data, as a tool for dealing with differences that may be ascribed to the anatomical variability of the subjects, to inaccuracies in the localisation of the voxel or slab, or to movement, rather than to the pathology under investigation. The aim was to develop an analysis procedure that can be consistently and reliably applied in the follow up of brain tumour. In this study, we demonstrate that the inclusion of such variables in the data analysis of quantitative MRS is fundamentally important (especially in view of the reduced accuracy typical of MRS measures compared to other MRI techniques), reducing the occurrence of false positives.

Integrating artificial intelligence with real-time intracranial EEG monitoring to automate interictal identification of seizure onset zones in focal epilepsy.

PubMed

Varatharajah, Yogatheesan; Berry, Brent; Cimbalnik, Jan; Kremen, Vaclav; Van Gompel, Jamie; Stead, Matt; Brinkmann, Benjamin; Iyer, Ravishankar; Worrell, Gregory

2018-08-01

An ability to map seizure-generating brain tissue, i.e. the seizure onset zone (SOZ), without recording actual seizures could reduce the duration of invasive EEG monitoring for patients with drug-resistant epilepsy. A widely-adopted practice in the literature is to compare the incidence (events/time) of putative pathological electrophysiological biomarkers associated with epileptic brain tissue with the SOZ determined from spontaneous seizures recorded with intracranial EEG, primarily using a single biomarker. Clinical translation of the previous efforts suffers from their inability to generalize across multiple patients because of (a) the inter-patient variability and (b) the temporal variability in the epileptogenic activity. Here, we report an artificial intelligence-based approach for combining multiple interictal electrophysiological biomarkers and their temporal characteristics as a way of accounting for the above barriers and show that it can reliably identify seizure onset zones in a study cohort of 82 patients who underwent evaluation for drug-resistant epilepsy. Our investigation provides evidence that utilizing the complementary information provided by multiple electrophysiological biomarkers and their temporal characteristics can significantly improve the localization potential compared to previously published single-biomarker incidence-based approaches, resulting in an average area under ROC curve (AUC) value of 0.73 in a cohort of 82 patients. Our results also suggest that recording durations between 90 min and 2 h are sufficient to localize SOZs with accuracies that may prove clinically relevant. The successful validation of our approach on a large cohort of 82 patients warrants future investigation on the feasibility of utilizing intra-operative EEG monitoring and artificial intelligence to localize epileptogenic brain tissue. Broadly, our study demonstrates the use of artificial intelligence coupled with careful feature engineering in augmenting clinical decision making.

Autism BrainNet: A network of postmortem brain banks established to facilitate autism research.

PubMed

Amaral, David G; Anderson, Matthew P; Ansorge, Olaf; Chance, Steven; Hare, Carolyn; Hof, Patrick R; Miller, Melissa; Nagakura, Ikue; Pickett, Jane; Schumann, Cynthia; Tamminga, Carol

2018-01-01

Autism spectrum disorder (ASD or autism) is a neurodevelopmental condition that affects over 1% of the population worldwide. Developing effective preventions and treatments for autism will depend on understanding the genetic perturbations and underlying neuropathology of the disorder. While evidence from magnetic resonance imaging and other noninvasive techniques points to altered development and organization of the autistic brain, these tools lack the resolution for identifying the cellular and molecular underpinnings of the disorder. Postmortem studies of high-quality human brain tissue currently represent the only viable option to pursuing these types of studies. However, the availability of high-quality ASD brain tissue has been extremely limited. Here we describe the establishment of a privately funded tissue bank, Autism BrainNet, a network of brain collection sites that work in a coordinated fashion to develop an adequate library of human postmortem brain tissues. Autism BrainNet was initiated as a collaboration between the Simons Foundation and Autism Speaks, and is currently funded by the Simons Foundation Autism Research Initiative. Autism BrainNet has collection sites (nodes) in California, Texas, New York, and Massachusetts; an affiliated, international node is located in Oxford, England. All donations to this network become part of a consolidated pool of tissue that is distributed to qualified investigators worldwide to carry out autism research. An essential component of this program is a widespread outreach program that highlights the need for postmortem brain donations to families affected by autism, led by the Autism Science Foundation. Challenges include an outreach campaign that deals with a disorder beginning in early childhood, collecting an adequate number of donations to deal with the high level of biologic heterogeneity of autism, and preparing this limited resource for optimal distribution to the greatest number of investigators. Copyright © 2018 Elsevier B.V. All rights reserved.