Estrogen synthesis and signaling pathways during ageing: from periphery to brain

PubMed Central

Cui, Jie; Shen, Yong; Li, Rena

2012-01-01

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 tissue as liver, heart, muscle, bone and brain. The tissue-specific estrogen synthesis is consistent with a diversity of estrogen actions. Here, we will focus on tissue and cell-specific estrogen synthesis and estrogen receptor signaling. This review will include three parts: (I) tissue and cell-specific estrogen synthesis and metabolism, (II) tissue and cell-specific distribution of estrogen receptors and signaling and (III) tissue-specific estrogen function and related disorders, including cardiovascular diseases, osteoporosis, Alzheimer's disease and Parkinson disease. This comprehensive review provides new insights into estrogens by giving a better understanding of the tissue-specific estrogen effects and their roles in various diseases. PMID:23348042

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.

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.

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.

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

Alzheimer's Disease. LC Science Tracer Bullet 87-2.

ERIC Educational Resources Information Center

Sammons, Vivian O., Comp.

Alzheimer's disease is characterized by a degeneration and shrinkage of brain tissue; the symptoms include progressive memory loss, bizarre behavior, difficulty in speaking and walking, incontinence, and confusion. Positive diagnosis is possible only upon examination of brain tissue at autopsy. The disease affects not only the patient but also the…

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.

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

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.

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.

Characterization of a Raman spectroscopy probe system for intraoperative brain tissue classification

PubMed Central

Desroches, Joannie; Jermyn, Michael; Mok, Kelvin; Lemieux-Leduc, Cédric; Mercier, Jeanne; St-Arnaud, Karl; Urmey, Kirk; Guiot, Marie-Christine; Marple, Eric; Petrecca, Kevin; Leblond, Frédéric

2015-01-01

A detailed characterization study is presented of a Raman spectroscopy system designed to maximize the volume of resected cancer tissue in glioma surgery based on in vivo molecular tissue characterization. It consists of a hand-held probe system measuring spectrally resolved inelastically scattered light interacting with tissue, designed and optimized for in vivo measurements. Factors such as linearity of the signal with integration time and laser power, and their impact on signal to noise ratio, are studied leading to optimal data acquisition parameters. The impact of ambient light sources in the operating room is assessed and recommendations made for optimal operating conditions. In vivo Raman spectra of normal brain, cancer and necrotic tissue were measured in 10 patients, demonstrating that real-time inelastic scattering measurements can distinguish necrosis from vital tissue (including tumor and normal brain tissue) with an accuracy of 87%, a sensitivity of 84% and a specificity of 89%. PMID:26203368

Effect of neuromonitor-guided titrated care on brain tissue hypoxia after opioid overdose cardiac arrest.

PubMed

Elmer, Jonathan; Flickinger, Katharyn L; Anderson, Maighdlin W; Koller, Allison C; Sundermann, Matthew L; Dezfulian, Cameron; Okonkwo, David O; Shutter, Lori A; Salcido, David D; Callaway, Clifton W; Menegazzi, James J

2018-04-18

Brain tissue hypoxia may contribute to preventable secondary brain injury after cardiac arrest. We developed a porcine model of opioid overdose cardiac arrest and post-arrest care including invasive, multimodal neurological monitoring of regional brain physiology. We hypothesized brain tissue hypoxia is common with usual post-arrest care and can be prevented by modifying mean arterial pressure (MAP) and arterial oxygen concentration (PaO 2 ). We induced opioid overdose and cardiac arrest in sixteen swine, attempted resuscitation after 9 min of apnea, and randomized resuscitated animals to three alternating 6-h blocks of standard or titrated care. We invasively monitored physiological parameters including brain tissue oxygen (PbtO 2 ). During standard care blocks, we maintained MAP > 65 mmHg and oxygen saturation 94-98%. During titrated care, we targeted PbtO2 > 20 mmHg. Overall, 10 animals (63%) achieved ROSC after a median of 12.4 min (range 10.8-21.5 min). PbtO 2 was higher during titrated care than standard care blocks (unadjusted β = 0.60, 95% confidence interval (CI) 0.42-0.78, P < 0.001). In an adjusted model controlling for MAP, vasopressors, sedation, and block sequence, PbtO 2 remained higher during titrated care (adjusted β = 0.75, 95%CI 0.43-1.06, P < 0.001). At three predetermined thresholds, brain tissue hypoxia was significantly less common during titrated care blocks (44 vs 2% of the block duration spent below 20 mmHg, P < 0.001; 21 vs 0% below 15 mmHg, P < 0.001; and, 7 vs 0% below 10 mmHg, P = .01). In this model of opioid overdose cardiac arrest, brain tissue hypoxia is common and treatable. Further work will elucidate best strategies and impact of titrated care on functional outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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.

Reflection imaging of China ink-perfused brain vasculature using confocal laser-scanning microscopy after clarification of brain tissue by the Spalteholz method.

PubMed

Gutierre, R C; Vannucci Campos, D; Mortara, R A; Coppi, A A; Arida, R M

2017-04-01

Confocal laser-scanning microscopy is a useful tool for visualizing neurons and glia in transparent preparations of brain tissue from laboratory animals. Currently, imaging capillaries and venules in transparent brain tissues requires the use of fluorescent proteins. Here, we show that vessels can be imaged by confocal laser-scanning microscopy in transparent cortical, hippocampal and cerebellar preparations after clarification of China ink-injected specimens by the Spalteholz method. This method may be suitable for global, three-dimensional, quantitative analyses of vessels, including stereological estimations of total volume and length and of surface area of vessels, which constitute indirect approaches to investigate angiogenesis. © 2017 Anatomical Society.

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.

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

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.

Brain tissues atrophy is not always the best structural biomarker of physiological aging: A multimodal cross-sectional study.

PubMed

Cherubini, Andrea; Caligiuri, Maria Eugenia; Péran, Patrice; Sabatini, Umberto; Cosentino, Carlo; Amato, Francesco

2015-01-01

This study presents a voxel-based multiple regression analysis of different magnetic resonance image modalities, including anatomical T1-weighted, T2* relaxometry, and diffusion tensor imaging. Quantitative parameters sensitive to complementary brain tissue alterations, including morphometric atrophy, mineralization, microstructural damage, and anisotropy loss, were compared in a linear physiological aging model in 140 healthy subjects (range 20-74 years). The performance of different predictors and the identification of the best biomarker of age-induced structural variation were compared without a priori anatomical knowledge. The best quantitative predictors in several brain regions were iron deposition and microstructural damage, rather than macroscopic tissue atrophy. Age variations were best resolved with a combination of markers, suggesting that multiple predictors better capture age-induced tissue alterations. These findings highlight the importance of a combined evaluation of multimodal biomarkers for the study of aging and point to a number of novel applications for the method described.

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.

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

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.

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

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.

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.

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.

Shear wave propagation in anisotropic soft tissues and gels

PubMed Central

Namani, Ravi; Bayly, Philip V.

2013-01-01

The propagation of shear waves in soft tissue can be visualized by magnetic resonance elastography (MRE) [1] to characterize tissue mechanical properties. Dynamic deformation of brain tissue arising from shear wave propagation may underlie the pathology of blast-induced traumatic brain injury. White matter in the brain, like other biological materials, exhibits a transversely isotropic structure, due to the arrangement of parallel fibers. Appropriate mathematical models and well-characterized experimental systems are needed to understand wave propagation in these structures. In this paper we review the theory behind waves in anisotropic, soft materials, including small-amplitude waves superimposed on finite deformation of a nonlinear hyperelastic material. Some predictions of this theory are confirmed in experimental studies of a soft material with controlled anisotropy: magnetically-aligned fibrin gel. PMID:19963987

Preparation of Purified Gram-positive Bacterial Cell Wall and Detection in Placenta and Fetal Tissues

PubMed Central

Mann, Beth; Loh, Lip Nam; Gao, Geli; Tuomanen, Elaine

2017-01-01

Cell wall is a complex biopolymer on the surface of all Gram-positive bacteria. During infection, cell wall is recognized by the innate immune receptor Toll-like receptor 2 causing intense inflammation and tissue damage. In animal models, cell wall traffics from the blood stream to many organs in the body, including brain, heart, placenta and fetus. This protocol describes how to prepare purified cell wall from Streptococcus pneumoniae, detect its distribution in animal tissues, and study the tissue response using the placenta and fetal brain as examples. PMID:28573167

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.

Plasticity of Nonneuronal Brain Tissue: Roles in Developmental Disorders

ERIC Educational Resources Information Center

Dong, Willie K.; Greenough, William T.

2004-01-01

Neuronal and nonneuronal plasticity are both affected by environmental and experiential factors. Remodeling of existing neurons induced by such factors has been observed throughout the brain, and includes alterations in dendritic field dimensions, synaptogenesis, and synaptic morphology. The brain loci affected by these plastic neuronal changes…

Crystals in brain and meninges in primary hyperoxaluria and oxalosis.

PubMed Central

Haqqani, M T

1977-01-01

A case of primary hyperoxaluria and oxalosis with chronic renal failure, crystalline myocarditis, and disseminated calcium oxalate crystal deposition in various tissues including the brain and meninges is described. Deposition of crystals in brain and meninges is exceptionally rare in primary oxalosis. Images PMID:838867

Genetics Home Reference: acrocallosal syndrome

MedlinePlus

... callosum occurs when the tissue that connects the left and right halves of the brain (the corpus callosum ) fails to form normally during the early stages of development before birth. Other brain abnormalities, including the growth ...

Influence of gravity for optimal head positions in the treatment of head injury patients.

PubMed

Li, Xiaogai; von Holst, Hans; Kleiven, Svein

2011-10-01

Brain edema is a major neurological complication of traumatic brain injury (TBI), commonly including a pathologically increased intracranial pressure (ICP) associated with poor outcome. In this study, gravitational force is suggested to have a significant impact on the pressure of the edema zone in the brain tissue and the objective of the study was to investigate the significance of head position on edema at the posterior part of the brain using a finite element (FE) model. A detailed FE model including the meninges, brain tissue and a fully connected cerebrospinal fluid (CSF) system was used in this study. Brain tissue was modelled as a poroelastic material consisting of an elastic solid skeleton composed of neurons and neuroglia, permeated by interstitial fluid. The effect of head positions (supine and prone position) due to gravity was investigated for a localized brain edema at the posterior part of the brain. The water content increment at the edema zone remained nearly identical for both positions. However, the interstitial fluid pressure (IFP) inside the edema zone decreased around 15% by having the head in a prone position compared with a supine position. The decrease of IFP inside the edema zone by changing patient position from supine to prone has the potential to alleviate the damage to central nervous system nerves. These observations indicate that considering the patient's head position during intensive care and at rehabilitation might be of importance to the treatment of edematous regions in TBI patients.

The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication

PubMed Central

Ouzzine, Mohamed; Gulberti, Sandrine; Ramalanjaona, Nick; Magdalou, Jacques; Fournel-Gigleux, Sylvie

2014-01-01

UDP-glucuronosyltransferases (UGTs) form a multigenic family of membrane-bound enzymes expressed in various tissues, including brain. They catalyze the formation of β-D-glucuronides from structurally unrelated substances (drugs, other xenobiotics, as well as endogenous compounds) by the linkage of glucuronic acid from the high energy donor, UDP-α-D-glucuronic acid. In brain, UGTs actively participate to the overall protection of the tissue against the intrusion of potentially harmful lipophilic substances that are metabolized as hydrophilic glucuronides. These metabolites are generally inactive, except for important pharmacologically glucuronides such as morphine-6-glucuronide. UGTs are mainly expressed in endothelial cells and astrocytes of the blood brain barrier (BBB). They are also associated to brain interfaces devoid of BBB, such as circumventricular organ, pineal gland, pituitary gland and neuro-olfactory tissues. Beside their key-role as a detoxication barrier, UGTs play a role in the steady-state of endogenous compounds, like steroids or dopamine (DA) that participate to the function of the brain. UGT isoforms of family 1A, 2A, 2B and 3A are expressed in brain tissues to various levels and are known to present distinct but overlapping substrate specificity. The importance of these enzyme species with regard to the formation of toxic, pharmacologically or physiologically relevant glucuronides in the brain will be discussed. PMID:25389387

Imaging Effects of Neurotrophic Factor Genes on Brain Plasticity and Repair in Multiple Sclerosis

DTIC Science & Technology

2012-07-01

sensitive to focal and diffuse changes in brain tissue (including cortical thickness and subcortical volume measures, lesion volumetry , and voxel-based...sensitive to both focal and diffuse effects in gray and white matter, including cortical thickness and subcortical volume measures, lesion volumetry , and

Banking for the future: an Australian experience in brain banking.

PubMed

Sarris, M; Garrick, T M; Sheedy, D; Harper, C G

2002-06-01

The New South Wales (NSW) Tissue Resource Centre (TRC) has been set up to provide Australian and international researchers with fixed and frozen brain tissue from cases that are well characterised, both clinically and pathologically, for projects related to neuropsychiatric and alcohol-related disorders. A daily review of the Department of Forensic Medicine provides initial information regarding a potential collection. If the case adheres to the strict inclusion criteria, the pathologist performing the postmortem examination is approached regarding retention of the brain tissue. The next of kin of the deceased is then contacted requesting permission to retain the brain for medical research. Cases are also obtained through donor programmes, where donors are assessed and consent to donate their brain during life. Once the brain is removed at autopsy, the brain is photographed, weighed and the volume determined, the brainstem and cerebellum are removed. The two hemispheres are divided, one hemisphere is fresh frozen and one fixed (randomised). Prior to freezing, the hemisphere is sliced into 1-cm coronal slices and a set of critical area blocks is taken. All frozen tissues are kept bagged at -80 degrees C. The other hemisphere is fixed in 15% buffered formalin for 2 weeks, embedded in agar and sliced at 3-mm intervals in the coronal plane. Tissue blocks from these slices are used for neuropathological analysis to exclude any other pathology. The TRC currently has 230 cases of both fixed and frozen material that has proven useful in a range of techniques in many research projects. These techniques include quantitative analyses of brain regions using neuropathological, neurochemical, neuropharmacological and gene expression assays.

Effects of pregnancy on the solubility of halogenated volatile anaesthetics in rat blood and tissues.

PubMed

Rao, Y; Wang, Y L; Li, H; Zhang, W; Liu, J

2008-11-01

This study was designed to evaluate the effects of pregnancy on the solubility of halogenated volatile anaesthetics in rat blood and tissues. Tissue samples from 10 pregnant and 10 non-pregnant adult female Sprague Dawley rats, including the heart, liver, kidney and brain, were obtained and made into respective homogenates. Blood/gas and tissue/gas partition coefficients for halothane, sevoflurane and isoflurane were determined by the method of two-stage headspace equilibration by gas chromatography with each of the homogenates. Values were analysed by t-test or one-way analysis of variance. The solubility within blood and brain for halothane in the pregnant group (2.90 +/- 0.44, 5.55 +/- 0.73) was significantly lower than that of the non-pregnant group (3.42 +/- 023, 6.33 +/- 0.64; P < 0.05). However, there were no significant differences between the two groups for liver, kidney or heart solubility. For sevoflurane and isoflurane, there were no significant differences in solubility between the two groups. In conclusion, pregnancy decreased the solubility of halothane within the blood and brain, whereas the solubility of halothane in other tissues including the liver, kidney and heart showed no significant alteration. Pregnancy did not affect the solubility ofsevoflurane or isoflurane within blood or the other tissues studied.

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.

Brain tissue deforms similarly to filled elastomers and follows consolidation theory

NASA Astrophysics Data System (ADS)

Franceschini, G.; Bigoni, D.; Regitnig, P.; Holzapfel, G. A.

2006-12-01

Slow, large deformations of human brain tissue—accompanying cranial vault deformation induced by positional plagiocephaly, occurring during hydrocephalus, and in the convolutional development—has surprisingly received scarce mechanical investigation. Since the effects of these deformations may be important, we performed a systematic series of in vitro experiments on human brain tissue, revealing the following features. (i) Under uniaxial (quasi-static), cyclic loading, brain tissue exhibits a peculiar nonlinear mechanical behaviour, exhibiting hysteresis, Mullins effect and residual strain, qualitatively similar to that observed in filled elastomers. As a consequence, the loading and unloading uniaxial curves have been found to follow the Ogden nonlinear elastic theory of rubber (and its variants to include Mullins effect and permanent strain). (ii) Loaded up to failure, the "shape" of the stress/strain curve qualitatively changes, evidencing softening related to local failure. (iii) Uniaxial (quasi-static) strain experiments under controlled drainage conditions provide the first direct evidence that the tissue obeys consolidation theory involving fluid migration, with properties similar to fine soils, but having much smaller volumetric compressibility. (iv) Our experimental findings also support the existence of a viscous component of the solid phase deformation. Brain tissue should, therefore, be modelled as a porous, fluid-saturated, nonlinear solid with very small volumetric (drained) compressibility.

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.

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.

Expansion of Multipotent Stem Cells from the Adult Human Brain

PubMed Central

Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

2013-01-01

The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

Proteomics analyses for the global proteins in the brain tissues of different human prion diseases.

PubMed

Shi, Qi; Chen, Li-Na; Zhang, Bao-Yun; Xiao, Kang; Zhou, Wei; Chen, Cao; Zhang, Xiao-Mei; Tian, Chan; Gao, Chen; Wang, Jing; Han, Jun; Dong, Xiao-Ping

2015-04-01

Proteomics changes of brain tissues have been described in different neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the brain proteomics of human prion disease remains less understood. In the study, the proteomics patterns of cortex and cerebellum of brain tissues of sporadic Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD were analyzed with isobaric tags for relative and absolute quantitation combined with multidimensional liquid chromatography and MS analysis, with the brains from three normal individuals as controls. Global protein profiling, significant pathway, and functional categories were analyzed. In total, 2287 proteins were identified with quantitative information both in cortex and cerebellum regions. Cerebellum tissues appeared to contain more up- and down-regulated proteins (727 proteins) than cortex regions (312 proteins) of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD. Viral myocarditis, Parkinson's disease, Alzheimer's disease, lysosome, oxidative phosphorylation, protein export, and drug metabolism-cytochrome P450 were the most commonly affected pathways of the three kinds of diseases. Almost coincident biological functions were identified in the brain tissues of the three diseases. In all, data here demonstrate that the brain tissues of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD have obvious proteomics changes at their terminal stages, which show the similarities not only among human prion diseases but also with other neurodegeneration diseases. This is the first study to provide a reference proteome map for human prion diseases and will be helpful for future studies focused on potential biomarkers for the diagnosis and therapy of human prion diseases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

Calculation of Absorbed Dose in Target Tissue and Equivalent Dose in Sensitive Tissues of Patients Treated by BNCT Using MCNP4C

NASA Astrophysics Data System (ADS)

Zamani, M.; Kasesaz, Y.; Khalafi, H.; Pooya, S. M. Hosseini

Boron Neutron Capture Therapy (BNCT) is used for treatment of many diseases, including brain tumors, in many medical centers. In this method, a target area (e.g., head of patient) is irradiated by some optimized and suitable neutron fields such as research nuclear reactors. Aiming at protection of healthy tissues which are located in the vicinity of irradiated tissue, and based on the ALARA principle, it is required to prevent unnecessary exposure of these vital organs. In this study, by using numerical simulation method (MCNP4C Code), the absorbed dose in target tissue and the equiavalent dose in different sensitive tissues of a patiant treated by BNCT, are calculated. For this purpose, we have used the parameters of MIRD Standard Phantom. Equiavelent dose in 11 sensitive organs, located in the vicinity of target, and total equivalent dose in whole body, have been calculated. The results show that the absorbed dose in tumor and normal tissue of brain equal to 30.35 Gy and 0.19 Gy, respectively. Also, total equivalent dose in 11 sensitive organs, other than tumor and normal tissue of brain, is equal to 14 mGy. The maximum equivalent doses in organs, other than brain and tumor, appear to the tissues of lungs and thyroid and are equal to 7.35 mSv and 3.00 mSv, respectively.

Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues.

PubMed

Anafi, Ron C; Pellegrino, Renata; Shockley, Keith R; Romer, Micah; Tufik, Sergio; Pack, Allan I

2013-05-30

Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times. In each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the influence of an artificial deprivation protocol, we identified a subset of these transcripts as specifically sleep-enhanced or sleep-repressed by requiring that their expression also change over the course of unperturbed sleep. 3% and 6% of the assayed transcripts showed "sleep specific" changes in the lung and heart respectively. Sleep specific transcripts in these tissues demonstrated highly significant overlap and shared temporal dynamics. Markers of cellular stress and the unfolded protein response were reduced during sleep in both tissues. These results mirror previous findings in brain. Sleep-enhanced pathways reflected the unique metabolic functions of each tissue. Transcripts related to carbohydrate and sulfur metabolic processes were enhanced by sleep in the lung, and collectively favor buffering from oxidative stress. DNA repair and protein metabolism annotations were significantly enriched among the sleep-enhanced transcripts in the heart. Our results also suggest that sleep may provide a Zeitgeber, or synchronizing cue, in the lung as a large cluster of transcripts demonstrated systematic changes in inter-animal variability as a function of both sleep duration and circadian time. Our data support the notion that the molecular consequences of sleep/wake behavioral state extend beyond the brain to include peripheral tissues. Sleep state induces a highly overlapping response in both heart and lung. We conclude that sleep enhances organ specific molecular functions and that it has a ubiquitous role in reducing cellular metabolic stress in both brain and peripheral tissues. Finally, our data suggest a novel role for sleep in synchronizing transcription in peripheral tissues.

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.

White Matter Glial Pathology in Autism

DTIC Science & Technology

2014-09-01

Autism 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0302 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Gregory A. Ordway...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Methods used to directly study the autism brain include brain imaging in living patients and...pathology studies using postmortem brain tissues from deceased autism spectrum disorder (ASD) donors. These methods typically focus on brain regions

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

Effect of intravenous gadolinium-DTPA on diffusion-weighted imaging of brain tumors: a short temporal interval assessment.

PubMed

Li, Xiang; Qu, Jin-Rong; Luo, Jun-Peng; Li, Jing; Zhang, Hong-Kai; Shao, Nan-Nan; Kwok, Keith; Zhang, Shou-Ning; Li, Yan-le; Liu, Cui-Cui; Zee, Chi-Shing; Li, Hai-Liang

2014-09-01

To determine the effect of intravenous administration of gadolinium (Gd) contrast medium (Gd-DTPA) on diffusion-weighted imaging (DWI) for the evaluation of normal brain parenchyma vs. brain tumor following a short temporal interval. Forty-four DWI studies using b values of 0 and 1000 s/mm(2) were performed before, immediately after, 1 min after, 3 min after, and 5 min after the administration of Gd-DTPA on 62 separate lesions including 15 meningioma, 17 glioma and 30 metastatic lesions. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and apparent diffusion coefficient (ADC) values of the brain tumor lesions and normal brain tissues were measured on pre- and postcontrast images. Statistical analysis using paired t-test between precontrast and postcontrast data were obtained on three brain tumors and normal brain tissue. The SNR and CNR of brain tumors and the SNR of normal brain tissue showed no statistical differences between pre- and postcontrast (P > 0.05). The ADC values on the three cases of brain tumors demonstrated significant initial increase on the immediate time point (P < 0.01) and decrease on following the 1 min time point (P < 0.01) after contrast. Significant decrease of ADC value was still found at 3min and 5min time point in the meningioma group (P < 0.01) with gradual normalization over time. The ADC values of normal brain tissues demonstrated significant initial elevation on the immediately postcontrast DWI sequence (P < 0.01). Contrast medium can cause a slight but statistically significant change on the ADC value within a short temporal interval after the contrast administration. The effect is both time and lesion-type dependent. © 2013 Wiley Periodicals, Inc.

Improving the modelling of irradiation-induced brain activation for in vivo PET verification of proton therapy.

PubMed

Bauer, Julia; Chen, Wenjing; Nischwitz, Sebastian; Liebl, Jakob; Rieken, Stefan; Welzel, Thomas; Debus, Juergen; Parodi, Katia

2018-04-24

A reliable Monte Carlo prediction of proton-induced brain tissue activation used for comparison to particle therapy positron-emission-tomography (PT-PET) measurements is crucial for in vivo treatment verification. Major limitations of current approaches to overcome include the CT-based patient model and the description of activity washout due to tissue perfusion. Two approaches were studied to improve the activity prediction for brain irradiation: (i) a refined patient model using tissue classification based on MR information and (ii) a PT-PET data-driven refinement of washout model parameters. Improvements of the activity predictions compared to post-treatment PT-PET measurements were assessed in terms of activity profile similarity for six patients treated with a single or two almost parallel fields delivered by active proton beam scanning. The refined patient model yields a generally higher similarity for most of the patients, except in highly pathological areas leading to tissue misclassification. Using washout model parameters deduced from clinical patient data could considerably improve the activity profile similarity for all patients. Current methods used to predict proton-induced brain tissue activation can be improved with MR-based tissue classification and data-driven washout parameters, thus providing a more reliable basis for PT-PET verification. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification of Insulin Receptor Splice Variant B in Neurons by in situ Detection in Human Brain Samples.

PubMed

Spencer, Brian; Rank, Logan; Metcalf, Jeff; Desplats, Paula

2018-03-06

Insulin and its receptor are widely expressed in a variety of tissues throughout the body including liver, adipose tissue, liver and brain. The insulin receptor is expressed as two functionally distinct isoforms, differentiated by a single 12 amino acid exon. The two receptor isoforms, designated IR/A and IR/B, are expressed in a highly tissue and cell specific manner and relative proportions of the different isoforms vary during development, aging and disease states. The high degree of similarity between the two isoforms has prevented detailed studies as differentiation of the two isoforms by traditional immunological methods cannot be achieved. We describe here a new in situ RT-PCR/ FISH assay that allows for the visualization of IR/A and IR/B in tissue along with tissue specific markers. We used this new method to show for the first time that IR/A and IR/B are both expressed in neurons in the adult human brain. Thus, we present a method that enables the investigation of IR/A and IR/B insulin receptor isoform expression in situ in various 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

Breaking ignorance: the case of the brain.

PubMed

Wekerle, H

2006-01-01

Immunological self-tolerance is maintained through diverse mechanisms, including deletion of autoreactive immune cells following confrontation with autoantigen in the thymus or in the periphery and active suppression by regulatory cells. A third way to prevent autoimmunity is by hiding self tissues behind a tissue barrier impermeable for circulating immune cells. The latter mechanism has been held responsible for self-tolerance within the nervous tissue. Indeed, the nervous tissues enjoy a conditionally privileged immune status: they are normally unreachable for self-reactive T and B cells, they lack lymphatic drainage, and they are deficient in local antigen-presenting cells. Yet the immune system is by no means fully ignorant of the nervous structures. An ever-growing number of brain specific autoantigens is expressed within the thymus, which ensures an early confrontation with the unfolding T cell repertoire, and there is evidence that B cells also contact CNS-like structures outside of the brain. Then pathological processes such as neurodegeneration commonly lift the brain's immune privilege, shifting the local milieus from immune-hostile to immune-friendly. Finally, brain-reactive T cells, which abound in the healthy immune repertoire, but remain innocuous throughout life, can be activated and gain access to their target tissues. On their way, they take an ordered migration through peripheral lymphoid tissues and blood circulation, and undergo a profound reprogramming of their gene expression profile, which renders them fit to enter the nervous system and to interact with local cellule elements.

Real time analysis of brain tissue by direct combination of ultrasonic surgical aspiration and sonic spray mass spectrometry.

PubMed

Schäfer, Karl-Christian; Balog, Júlia; Szaniszló, Tamás; Szalay, Dániel; Mezey, Géza; Dénes, Júlia; Bognár, László; Oertel, Matthias; Takáts, Zoltán

2011-10-15

Direct combination of cavitron ultrasonic surgical aspirator (CUSA) and sonic spray ionization mass spectrometry is presented. A commercially available ultrasonic surgical device was coupled to a Venturi easy ambient sonic-spray ionization (V-EASI) source by directly introducing liquified tissue debris into the Venturi air jet pump. The Venturi air jet pump was found to efficiently nebulize the suspended tissue material for gas phase ion production. The ionization mechanism involving solely pneumatic spraying was associated with that of sonic spray ionization. Positive and negative ionization spectra were obtained from brain and liver samples reflecting the primary application areas of the surgical device. Mass spectra were found to feature predominantly complex lipid-type constituents of tissues in both ion polarity modes. Multiply charged peptide anions were also detected. The influence of instrumental settings was characterized in detail. Venturi pump geometry and flow parameters were found to be critically important in ionization efficiency. Standard solutions of phospholipids and peptides were analyzed in order to test the dynamic range, sensitivity, and suppression effects. The spectra of the intact tissue specimens were found to be highly specific to the histological tissue type. The principal component analysis (PCA) and linear discriminant analysis (LDA) based data analysis method was developed for real-time tissue identification in a surgical environment. The method has been successfully tested on post-mortem and ex vivo human samples including astrocytomas, meningeomas, metastatic brain tumors, and healthy brain tissue. © 2011 American Chemical Society

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

Mesh Nanoelectronics: Seamless Integration of Electronics with Tissues.

PubMed

Dai, Xiaochuan; Hong, Guosong; Gao, Teng; Lieber, Charles M

2018-02-20

Nanobioelectronics represents a rapidly developing field with broad-ranging opportunities in fundamental biological sciences, biotechnology, and medicine. Despite this potential, seamless integration of electronics has been difficult due to fundamental mismatches, including size and mechanical properties, between the elements of the electronic and living biological systems. In this Account, we discuss the concept, development, key demonstrations, and future opportunities of mesh nanoelectronics as a general paradigm for seamless integration of electronics within synthetic tissues and live animals. We first describe the design and realization of hybrid synthetic tissues that are innervated in three dimensions (3D) with mesh nanoelectronics where the mesh serves as both as a tissue scaffold and as a platform of addressable electronic devices for monitoring and manipulating tissue behavior. Specific examples of tissue/nanoelectronic mesh hybrids highlighted include 3D neural tissue, cardiac patches, and vascular constructs, where the nanoelectronic devices have been used to carry out real-time 3D recording of electrophysiological and chemical signals in the tissues. This novel platform was also exploited for time-dependent 3D spatiotemporal mapping of cardiac tissue action potentials during cell culture and tissue maturation as well as in response to injection of pharmacological agents. The extension to simultaneous real-time monitoring and active control of tissue behavior is further discussed for multifunctional mesh nanoelectronics incorporating both recording and stimulation devices, providing the unique capability of bidirectional interfaces to cardiac tissue. In the case of live animals, new challenges must be addressed, including minimally invasive implantation, absence of deleterious chronic tissue response, and long-term capability for monitoring and modulating tissue activity. We discuss each of these topics in the context of implantation of mesh nanoelectronics into rodent brains. First, we describe the design of ultraflexible mesh nanoelectronics with size features and mechanical properties similar to brain tissue and a novel syringe-injection methodology that allows the mesh nanoelectronics to be precisely delivered to targeted brain regions in a minimally invasive manner. Next, we discuss time-dependent histology studies showing seamless and stable integration of mesh nanoelectronics within brain tissue on at least one year scales without evidence of chronic immune response or glial scarring characteristic of conventional implants. Third, armed with facile input/output interfaces, we describe multiplexed single-unit recordings that demonstrate stable tracking of the same individual neurons and local neural circuits for at least 8 months, long-term monitoring and stimulation of the same groups of neurons, and following changes in individual neuron activity during brain aging. Moving forward, we foresee substantial opportunities for (1) continued development of mesh nanoelectronics through, for example, broadening nanodevice signal detection modalities and taking advantage of tissue-like properties for selective cell targeting and (2) exploiting the unique capabilities of mesh nanoelectronics for tackling critical scientific and medical challenges such as understanding and potentially ameliorating cell and circuit level changes associated with natural and pathological aging, as well as using mesh nanoelectronics as active tissue scaffolds for regenerative medicine and as neuroprosthetics for monitoring and treating neurological diseases.

Histopathological effects, responses of oxidative stress, inflammation, apoptosis biomarkers and alteration of gene expressions related to apoptosis, oxidative stress, and reproductive system in chlorpyrifos-exposed common carp (Cyprinus carpio L.).

PubMed

Altun, Serdar; Özdemir, Selçuk; Arslan, Harun

2017-11-01

In this study, we aimed to identify the toxic effects of chlorpyrifos exposure on the tissues of common carp. For this purpose, we evaluated histopathological changes in the brain, gills, liver, kidney, testis, and ovaries after 21 days of chlorpyrifos exposure. Activation of 8-OHdG, cleaved caspase-3, and iNOS were assesed by immunofluorescence assay in chlorpyrifos-exposed brain and liver tissue. Additionally, we measured the expression levels of caspase-3, caspase-8, iNOS, MT1, CYP1A, and CYP3A genes in chlorpyrifos-exposed brain tissue, as well as the expression levels of FSH and LH genes in chlorpyrifos-exposed ovaries, using qRT-PCR. We observed severe histopathological lesions, including inflammation, degeneration, necrosis, and hemorrhage, in the evaluated tissues of common carp after both high and low levels of exposure to chlorpyrifos. We detected strong and diffuse signs of immunofluorescence reaction for 8-OHdG, iNOS, and cleaved caspase-3 in the chlorpyrifos-exposed brain and liver tissues. Furthermore, we found that chlorpyrifos exposure significantly upregulated the expressions of caspase-3, caspase-8, iNOS, and MT1, and also moderately upregulated CYP1A and CYP3A in the brain tissue of exposed carp. We also noted downregulation of FSH and LH gene expressions in chlorpyrifos-exposed ovary tissues. Based on our results, chlorpyrifos toxication caused crucial histopathological lesions in vital organs, induced oxidative stress, inflammation, and apoptosis in liver and brain tissues, and triggered reproductive sterility in common carp. Therefore, we can propose that chlorpyrifos toxication is highly dangerous to the health of common carp. Moreover, chlorpyrifos pollution in the water could threaten the common carp population. Use of chlorpyrifos should be restricted, and aquatic systems should be monitored for chlorpyrifos pollution. Copyright © 2017 Elsevier Ltd. All rights reserved.

EFFECTS OF IRRADIATION ON BRAIN VASCULATURE USING AN IN SITU TUMOR MODEL

PubMed Central

Zawaski, Janice A.; Gaber, M. Waleed; Sabek, Omaima M.; Wilson, Christy M.; Duntsch, Christopher D.; Merchant, Thomas E.

2013-01-01

Purpose Damage to normal tissue is a limiting factor in clinical radiotherapy (RT). We tested the hypothesis that the presence of tumor alters the response of normal tissues to irradiation using a rat in situ brain tumor model. Methods and Materials Intravital microscopy was used with a rat cranial window to assess the in situ effect of rat C6 glioma on peritumoral tissue with and without RT. The RT regimen included 40 Gy at 8 Gy/day starting Day 5 after tumor implant. Endpoints included blood–brain barrier permeability, clearance index, leukocyte-endothelial interactions and staining for vascular endothelial growth factor (VEGF) glial fibrillary acidic protein, and apoptosis. To characterize the system response to RT, animal survival and tumor surface area and volume were measured. Sham experiments were performed on similar animals implanted with basement membrane matrix absent of tumor cells. Results The presence of tumor alone increases permeability but has little effect on leukocyte–endothelial interactions and astrogliosis. Radiation alone increases tissue permeability, leukocyte-endothelial interactions, and astrogliosis. The highest levels of permeability and cell adhesion were seen in the model that combined tumor and irradiation; however, the presence of tumor appeared to reduce the volume of rolling leukocytes. Unirradiated tumor and peritumoral tissue had poor clearance. Irradiated tumor and peritumoral tissue had a similar clearance index to irradiated and unirradiated sham-implanted animals. Radiation reduces the presence of VEGF in peritumoral normal tissues but did not affect the amount of apoptosis in the normal tissue. Apoptosis was identified in the tumor tissue with and without radiation. Conclusions We developed a novel approach to demonstrate that the presence of the tumor in a rat intracranial model alters the response of normal tissues to irradiation. PMID:22197233

A comparative study of dietary curcumin, nanocurcumin, and other classical amyloid-binding dyes for labeling and imaging of amyloid plaques in brain tissue of 5×-familial Alzheimer's disease mice.

PubMed

Maiti, Panchanan; Hall, Tia C; Paladugu, Leela; Kolli, Nivya; Learman, Cameron; Rossignol, Julien; Dunbar, Gary L

2016-11-01

Deposition of amyloid beta protein (Aβ) is a key component in the pathogenesis of Alzheimer's disease (AD). As an anti-amyloid natural polyphenol, curcumin (Cur) has been used as a therapy for AD. Its fluorescent activity, preferential binding to Aβ, as well as structural similarities with other traditional amyloid-binding dyes, make it a promising candidate for labeling and imaging of Aβ plaques in vivo. The present study was designed to test whether dietary Cur and nanocurcumin (NC) provide more sensitivity for labeling and imaging of Aβ plaques in brain tissues from the 5×-familial AD (5×FAD) mice than the classical Aβ-binding dyes, such as Congo red and Thioflavin-S. These comparisons were made in postmortem brain tissues from the 5×FAD mice. We observed that Cur and NC labeled Aβ plaques to the same degree as Aβ-specific antibody and to a greater extent than those of the classical amyloid-binding dyes. Cur and NC also labeled Aβ plaques in 5×FAD brain tissues when injected intraperitoneally. Nanomolar concentrations of Cur or NC are sufficient for labeling and imaging of Aβ plaques in 5×FAD brain tissue. Cur and NC also labeled different types of Aβ plaques, including core, neuritic, diffuse, and burned-out, to a greater degree than other amyloid-binding dyes. Therefore, Cur and or NC can be used as an alternative to Aβ-specific antibody for labeling and imaging of Aβ plaques ex vivo and in vivo. It can provide an easy and inexpensive means of detecting Aβ-plaque load in postmortem brain tissue of animal models of AD after anti-amyloid therapy.

9 CFR 319.702 - Lard, leaf lard.

Code of Federal Regulations, 2012 CFR

2012-01-01

... lard. (a) Lard is the fat rendered from clean and sound edible tissues from swine. The tissues may be... misbranding of the lard. The tissues shall be reasonably free from blood, and shall not include stomachs, livers, spleens, kidneys, and brains, or settlings and skimmings. “Leaf Lard” is lard prepared from fresh...

9 CFR 319.702 - Lard, leaf lard.

Code of Federal Regulations, 2010 CFR

2010-01-01

... lard. (a) Lard is the fat rendered from clean and sound edible tissues from swine. The tissues may be... misbranding of the lard. The tissues shall be reasonably free from blood, and shall not include stomachs, livers, spleens, kidneys, and brains, or settlings and skimmings. “Leaf Lard” is lard prepared from fresh...

9 CFR 319.702 - Lard, leaf lard.

Code of Federal Regulations, 2014 CFR

2014-01-01

... lard. (a) Lard is the fat rendered from clean and sound edible tissues from swine. The tissues may be... misbranding of the lard. The tissues shall be reasonably free from blood, and shall not include stomachs, livers, spleens, kidneys, and brains, or settlings and skimmings. “Leaf Lard” is lard prepared from fresh...

9 CFR 319.702 - Lard, leaf lard.

Code of Federal Regulations, 2013 CFR

2013-01-01

... lard. (a) Lard is the fat rendered from clean and sound edible tissues from swine. The tissues may be... misbranding of the lard. The tissues shall be reasonably free from blood, and shall not include stomachs, livers, spleens, kidneys, and brains, or settlings and skimmings. “Leaf Lard” is lard prepared from fresh...

9 CFR 319.702 - Lard, leaf lard.

Code of Federal Regulations, 2011 CFR

2011-01-01

... lard. (a) Lard is the fat rendered from clean and sound edible tissues from swine. The tissues may be... misbranding of the lard. The tissues shall be reasonably free from blood, and shall not include stomachs, livers, spleens, kidneys, and brains, or settlings and skimmings. “Leaf Lard” is lard prepared from fresh...

Role of Matricellular Proteins in Disorders of the Central Nervous System.

PubMed

Jayakumar, A R; Apeksha, A; Norenberg, M D

2017-03-01

Matricellular proteins (MCPs) are actively expressed non-structural proteins present in the extracellular matrix, which rapidly turnover and possess regulatory roles, as well as mediate cell-cell interactions. MCPs characteristically contain binding sites for other extracellular proteins, cell surface receptors, growth factors, cytokines and proteases, that provide structural support for surrounding cells. MCPs are present in most organs, including brain, and play a major role in cell-cell interactions and tissue repair. Among the MCPs found in brain include thrombospondin-1/2, secreted protein acidic and rich in cysteine family (SPARC), including Hevin/SC1, Tenascin C and CYR61/Connective Tissue Growth Factor/Nov family of proteins, glypicans, galectins, plasminogen activator inhibitor (PAI-1), autotaxin, fibulin and perisostin. This review summarizes the potential role of MCPs in the pathogenesis of major neurological disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, ischemia, trauma, hepatic encephalopathy, Down's syndrome, autism, multiple sclerosis, brain neoplasms, Parkinson's disease and epilepsy. Potential therapeutic opportunities of MCP's for these disorders are also considered in this review.

Detection of brain tumor margins using optical coherence tomography

NASA Astrophysics Data System (ADS)

Juarez-Chambi, Ronald M.; Kut, Carmen; Rico-Jimenez, Jesus; Campos-Delgado, Daniel U.; Quinones-Hinojosa, Alfredo; Li, Xingde; Jo, Javier

2018-02-01

In brain cancer surgery, it is critical to achieve extensive resection without compromising adjacent healthy, noncancerous regions. Various technological advances have made major contributions in imaging, including intraoperative magnetic imaging (MRI) and computed tomography (CT). However, these technologies have pros and cons in providing quantitative, real-time and three-dimensional (3D) continuous guidance in brain cancer detection. Optical Coherence Tomography (OCT) is a non-invasive, label-free, cost-effective technique capable of imaging tissue in three dimensions and real time. The purpose of this study is to reliably and efficiently discriminate between non-cancer and cancerinfiltrated brain regions using OCT images. To this end, a mathematical model for quantitative evaluation known as the Blind End-Member and Abundances Extraction method (BEAE). This BEAE method is a constrained optimization technique which extracts spatial information from volumetric OCT images. Using this novel method, we are able to discriminate between cancerous and non-cancerous tissues and using logistic regression as a classifier for automatic brain tumor margin detection. Using this technique, we are able to achieve excellent performance using an extensive cross-validation of the training dataset (sensitivity 92.91% and specificity 98.15%) and again using an independent, blinded validation dataset (sensitivity 92.91% and specificity 86.36%). In summary, BEAE is well-suited to differentiate brain tissue which could support the guiding surgery process for tissue resection.

Detection of brain tumor margins using optical coherence tomography

NASA Astrophysics Data System (ADS)

Juarez-Chambi, Ronald M.; Kut, Carmen; Rico-Jimenez, Jesus; Campos-Delgado, Daniel U.; Quinones-Hinojosa, Alfredo; Li, Xingde; Jo, Javier

2018-02-01

In brain cancer surgery, it is critical to achieve extensive resection without compromising adjacent healthy, non-cancerous regions. Various technological advances have made major contributions in imaging, including intraoperative magnetic imaging (MRI) and computed tomography (CT). However, these technologies have pros and cons in providing quantitative, real-time and three-dimensional (3D) continuous guidance in brain cancer detection. Optical Coherence Tomography (OCT) is a non-invasive, label-free, cost-effective technique capable of imaging tissue in three dimensions and real time. The purpose of this study is to reliably and efficiently discriminate between non-cancer and cancer-infiltrated brain regions using OCT images. To this end, a mathematical model for quantitative evaluation known as the Blind End- Member and Abundances Extraction method (BEAE). This BEAE method is a constrained optimization technique which extracts spatial information from volumetric OCT images. Using this novel method, we are able to discriminate between cancerous and non-cancerous tissues and using logistic regression as a classifier for automatic brain tumor margin detection. Using this technique, we are able to achieve excellent performance using an extensive cross-validation of the training dataset (sensitivity 92.91% and specificity 98.15%) and again using an independent, blinded validation dataset (sensitivity 92.91% and specificity 86.36%). In summary, BEAE is well-suited to differentiate brain tissue which could support the guiding surgery process for tissue resection.

Requirement for interleukin-1 to drive brain inflammation reveals tissue-specific mechanisms of innate immunity

PubMed Central

Giles, James A; Greenhalgh, Andrew D; Davies, Claire L; Denes, Adam; Shaw, Tovah; Coutts, Graham; Rothwell, Nancy J; McColl, Barry W; Allan, Stuart M

2015-01-01

The immune system is implicated in a wide range of disorders affecting the brain and is, therefore, an attractive target for therapy. Interleukin-1 (IL-1) is a potent regulator of the innate immune system important for host defense but is also associated with injury and disease in the brain. Here, we show that IL-1 is a key mediator driving an innate immune response to inflammatory challenge in the mouse brain but is dispensable in extracerebral tissues including the lung and peritoneum. We also demonstrate that IL-1α is an important ligand contributing to the CNS dependence on IL-1 and that IL-1 derived from the CNS compartment (most likely microglia) is the major source driving this effect. These data reveal previously unknown tissue-specific requirements for IL-1 in driving innate immunity and suggest that IL-1-mediated inflammation in the brain could be selectively targeted without compromising systemic innate immune responses that are important for resistance to infection. This property could be exploited to mitigate injury- and disease-associated inflammation in the brain without increasing susceptibility to systemic infection, an important complication in several neurological disorders. PMID:25367678

Characterization of cortical neuronal and glial alterations during culture of organotypic whole brain slices from neonatal and mature mice.

PubMed

Staal, Jerome A; Alexander, Samuel R; Liu, Yao; Dickson, Tracey D; Vickers, James C

2011-01-01

Organotypic brain slice culturing techniques are extensively used in a wide range of experimental procedures and are particularly useful in providing mechanistic insights into neurological disorders or injury. The cellular and morphological alterations associated with hippocampal brain slice cultures has been well established, however, the neuronal response of mouse cortical neurons to culture is not well documented. In the current study, we compared the cell viability, as well as phenotypic and protein expression changes in cortical neurons, in whole brain slice cultures from mouse neonates (P4-6), adolescent animals (P25-28) and mature adults (P50+). Cultures were prepared using the membrane interface method. Propidium iodide labeling of nuclei (due to compromised cell membrane) and AlamarBlue™ (cell respiration) analysis demonstrated that neonatal tissue was significantly less vulnerable to long-term culture in comparison to the more mature brain tissues. Cultures from P6 animals showed a significant increase in the expression of synaptic markers and a decrease in growth-associated proteins over the entire culture period. However, morphological analysis of organotypic brain slices cultured from neonatal tissue demonstrated that there were substantial changes to neuronal and glial organization within the neocortex, with a distinct loss of cytoarchitectural stratification and increased GFAP expression (p<0.05). Additionally, cultures from neonatal tissue had no glial limitans and, after 14 DIV, displayed substantial cellular protrusions from slice edges, including cells that expressed both glial and neuronal markers. In summary, we present a substantial evaluation of the viability and morphological changes that occur in the neocortex of whole brain tissue cultures, from different ages, over an extended period of culture.

Feasibility of using diffuse reflectance spectroscopy for the quantification of brain edema

NASA Astrophysics Data System (ADS)

Rodriguez, Juan G.; Sisson, Cynthia; Hendricks, Chad; Pattillo, Chris; McWaters, Megan; Hardjasudarma, Mardjohan; Quarles, Chad; Yaroslavsky, Anna N.; Yaroslavsky, Ilya V.; Battarbee, Harold

2001-05-01

Many diseased states of the brain can result in the displacement of brain tissues and restrict cerebral blood flow, disrupting function in a life-threatening manner. Clinical examples where displacements are observed include venous thromboses, hematomas, strokes, tumors, abscesses, and, particularly, brain edema. For the latter, the brain tissue swells, displacing the cerebral spinal fluid (CSF) layer that surrounds it, eventually pressing itself against the skull. Under such conditions, catheters are often inserted into the brain's ventricles or the subarachnoid space to monitor increased pressure. These are invasive procedures that incur increased risk of infection and consequently are used reluctantly by clinicians. Recent studies in the field of biomedical optics have suggested that the presence or absence of the CSF layer can lead to dramatic changes in NIR signals obtained from diffuse reflectance measurements around the head. In this study, we consider how this sensitivity of NIR signals to CSF might be exploited to non-invasively monitor the onset and resolution of brain edema.

3D virtual histology at the host/parasite interface: visualisation of the master manipulator, Dicrocoelium dendriticum, in the brain of its ant host.

PubMed

Martín-Vega, Daniel; Garbout, Amin; Ahmed, Farah; Wicklein, Martina; Goater, Cameron P; Colwell, Douglas D; Hall, Martin J R

2018-06-05

Some parasites are able to manipulate the behaviour of their hosts to their own advantage. One of the most well-established textbook examples of host manipulation is that of the trematode Dicrocoelium dendriticum on ants, its second intermediate host. Infected ants harbour encysted metacercariae in the gaster and a non-encysted metacercaria in the suboesophageal ganglion (SOG); however, the mechanisms that D. dendriticum uses to manipulate the ant behaviour remain unknown, partly because of a lack of a proper and direct visualisation of the physical interface between the parasite and the ant brain tissue. Here we provide new insights into the potential mechanisms that this iconic manipulator uses to alter its host's behaviour by characterising the interface between D. dendriticum and the ant tissues with the use of non-invasive micro-CT scanning. For the first time, we show that there is a physical contact between the parasite and the ant brain tissue at the anteriormost part of the SOG, including in a case of multiple brain infection where only the parasite lodged in the most anterior part of the SOG was in contact with the ant brain tissue. We demonstrate the potential of micro-CT to further understand other parasite/host systems in parasitological research.

Demeclocycline as a contrast agent for detecting brain neoplasms using confocal microscopy

NASA Astrophysics Data System (ADS)

Wirth, Dennis; Smith, Thomas W.; Moser, Richard; Yaroslavsky, Anna N.

2015-04-01

Complete resection of brain tumors improves life expectancy and quality. Thus, there is a strong need for high-resolution detection and microscopically controlled removal of brain neoplasms. The goal of this study was to test demeclocycline as a contrast enhancer for the intraoperative detection of brain tumors. We have imaged benign and cancerous brain tumors using multimodal confocal microscopy. The tumors investigated included pituitary adenoma, meningiomas, glioblastomas, and metastatic brain cancers. Freshly excised brain tissues were stained in 0.75 mg ml-1 aqueous solution of demeclocyline. Reflectance images were acquired at 402 nm. Fluorescence signals were excited at 402 nm and registered between 500 and 540 nm. After imaging, histological sections were processed from the imaged specimens and compared to the optical images. Fluorescence images highlighted normal and cancerous brain cells, while reflectance images emphasized the morphology of connective tissue. The optical and histological images were in accordance with each other for all types of tumors investigated. Demeclocyline shows promise as a contrast agent for intraoperative detection of brain tumors.

The Epigenetic Link between Prenatal Adverse Environments and Neurodevelopmental Disorders

PubMed Central

Kundakovic, Marija; Jaric, Ivana

2017-01-01

Prenatal adverse environments, such as maternal stress, toxicological exposures, and viral infections, can disrupt normal brain development and contribute to neurodevelopmental disorders, including schizophrenia, depression, and autism. Increasing evidence shows that these short- and long-term effects of prenatal exposures on brain structure and function are mediated by epigenetic mechanisms. Animal studies demonstrate that prenatal exposure to stress, toxins, viral mimetics, and drugs induces lasting epigenetic changes in the brain, including genes encoding glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf). These epigenetic changes have been linked to changes in brain gene expression, stress reactivity, and behavior, and often times, these effects are shown to be dependent on the gestational window of exposure, sex, and exposure level. Although evidence from human studies is more limited, gestational exposure to environmental risks in humans is associated with epigenetic changes in peripheral tissues, and future studies are required to understand whether we can use peripheral biomarkers to predict neurobehavioral outcomes. An extensive research effort combining well-designed human and animal studies, with comprehensive epigenomic analyses of peripheral and brain tissues over time, will be necessary to improve our understanding of the epigenetic basis of neurodevelopmental disorders. PMID:28335457

Shorter sleep duration and better sleep quality are associated with greater tissue density in the brain.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Yokoyama, Ryoichi; Kotozaki, Yuka; Nakagawa, Seishu; Sekiguchi, Atsushi; Iizuka, Kunio; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Miyauchi, Carlos Makoto; Shinada, Takamitsu; Sakaki, Kohei; Nozawa, Takayuki; Ikeda, Shigeyuki; Yokota, Susumu; Daniele, Magistro; Sassa, Yuko; Kawashima, Ryuta

2018-04-11

Poor sleep quality is associated with unfavorable psychological measurements, whereas sleep duration has complex relationships with such measurements. The aim of this study was to identify the associations between microstructural properties of the brain and sleep duration/sleep quality in a young adult. The associations between mean diffusivity (MD), a measure of diffusion tensor imaging (DTI), and sleep duration/sleep quality were investigated in a study cohort of 1201 normal young adults. Positive correlations between sleep duration and MD of widespread areas of the brain, including the prefrontal cortex (PFC) and the dopaminergic systems, were identified. Negative correlations between sleep quality and MD of the widespread areas of the brain, including the PFC and the right hippocampus, were also detected. Lower MD has been previously associated with more neural tissues in the brain. Further, shorter sleep duration was associated with greater persistence and executive functioning (lower Stroop interference), whereas good sleep quality was associated with states and traits relevant to positive affects. These results suggest that bad sleep quality and longer sleep duration were associated with aberrant neurocognitive measurements in the brain in healthy young adults.

Tissue classification and diagnostics using a fiber probe for combined Raman and fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Cicchi, Riccardo; Anand, Suresh; Rossari, Susanna; Sturiale, Alessandro; Giordano, Flavio; De Giorgi, Vincenzo; Maio, Vincenza; Massi, Daniela; Nesi, Gabriella; Buccoliero, Anna Maria; Tonelli, Francesco; Guerrini, Renzo; Pimpinelli, Nicola; Pavone, Francesco S.

2015-03-01

Two different optical fiber probes for combined Raman and fluorescence spectroscopic measurements were designed, developed and used for tissue diagnostics. Two visible laser diodes were used for fluorescence spectroscopy, whereas a laser diode emitting in the NIR was used for Raman spectroscopy. The two probes were based on fiber bundles with a central multimode optical fiber, used for delivering light to the tissue, and 24 surrounding optical fibers for signal collection. Both fluorescence and Raman spectra were acquired using the same detection unit, based on a cooled CCD camera, connected to a spectrograph. The two probes were successfully employed for diagnostic purposes on various tissues in a good agreement with common routine histology. This study included skin, brain and bladder tissues and in particular the classification of: malignant melanoma against melanocytic lesions and healthy skin; urothelial carcinoma against healthy bladder mucosa; brain tumor against dysplastic brain tissue. The diagnostic capabilities were determined using a cross-validation method with a leave-one-out approach, finding very high sensitivity and specificity for all the examined tissues. The obtained results demonstrated that the multimodal approach is crucial for improving diagnostic capabilities. The system presented here can improve diagnostic capabilities on a broad range of tissues and has the potential of being used for endoscopic inspections in the near future.

Tissue classification and diagnostics using a fiber probe for combined Raman and fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Cicchi, Riccardo; Anand, Suresh; Crisci, Alfonso; Giordano, Flavio; Rossari, Susanna; De Giorgi, Vincenzo; Maio, Vincenza; Massi, Daniela; Nesi, Gabriella; Buccoliero, Anna Maria; Guerrini, Renzo; Pimpinelli, Nicola; Pavone, Francesco S.

2015-07-01

Two different optical fiber probes for combined Raman and fluorescence spectroscopic measurements were designed, developed and used for tissue diagnostics. Two visible laser diodes were used for fluorescence spectroscopy, whereas a laser diode emitting in the NIR was used for Raman spectroscopy. The two probes were based on fiber bundles with a central multimode optical fiber, used for delivering light to the tissue, and 24 surrounding optical fibers for signal collection. Both fluorescence and Raman spectra were acquired using the same detection unit, based on a cooled CCD camera, connected to a spectrograph. The two probes were successfully employed for diagnostic purposes on various tissues in a good agreement with common routine histology. This study included skin, brain and bladder tissues and in particular the classification of: malignant melanoma against melanocytic lesions and healthy skin; urothelial carcinoma against healthy bladder mucosa; brain tumor against dysplastic brain tissue. The diagnostic capabilities were determined using a cross-validation method with a leave-one-out approach, finding very high sensitivity and specificity for all the examined tissues. The obtained results demonstrated that the multimodal approach is crucial for improving diagnostic capabilities. The system presented here can improve diagnostic capabilities on a broad range of tissues and has the potential of being used for endoscopic inspections in the near future.

Review of MR Elastography Applications and Recent Developments

PubMed Central

Glaser, Kevin J.; Manduca, Armando; Ehman, Richard L.

2012-01-01

The technique of MR elastography (MRE) has emerged as a useful modality for quantitatively imaging the mechanical properties of soft tissues in vivo. Recently, MRE has been introduced as a clinical tool for evaluating chronic liver disease, but many other potential applications are being explored. These applications include measuring tissue changes associated with diseases of the liver, breast, brain, heart, and skeletal muscle including both focal lesions (e.g., hepatic, breast, and brain tumors) and diffuse diseases (e.g., fibrosis and multiple sclerosis). The purpose of this review article is to summarize some of the recent developments of MRE and to highlight some emerging applications. PMID:22987755

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.

Protective effects of some creatine derivatives in brain tissue anoxia.

PubMed

Perasso, Luisa; Lunardi, Gian Luigi; Risso, Federica; Pohvozcheva, Anna V; Leko, Maria V; Gandolfo, Carlo; Florio, Tullio; Cupello, Aroldo; Burov, Sergey V; Balestrino, Maurizio

2008-05-01

Some derivatives more lipophylic than creatine, thus theoretically being capable to better cross the blood-brain barrier, were studied for their protective effect in mouse hippocampal slices. We found that N-amidino-piperidine is harmful to brain tissue, and that phosphocreatine is ineffective. Creatine, creatine-Mg-complex (acetate) and phosphocreatine-Mg-complex (acetate) increased the latency to population spike disappearance during anoxia. Creatine and creatine-Mg-complex (acetate) also increased the latency of anoxic depolarization, while the delay induced by phosphocreatine-Mg-complex (acetate) was of borderline significance (P = 0.056). Phosphocreatine-Mg-complex (acetate) significantly reduced neuronal hyperexcitability during anoxia, an effect that no other compound (including creatine itself) showed. For all parameters except reduced hyperexcitability the effects statistically correlated with tissue levels of creatine or phosphocreatine. Summing up, exogenous phosphocreatine and N-amidino piperidine are not useful for brain protection, while chelates of both creatine and phosphocreatine do replicate some of the known protective effects of creatine. In addition, phosphocreatine-Mg-complex (acetate) also reduced neuronal hyperexcitability during anoxia.

Brain mesenchymal stem cells: The other stem cells of the brain?

PubMed

Appaix, Florence; Nissou, Marie-France; van der Sanden, Boudewijn; Dreyfus, Matthieu; Berger, François; Issartel, Jean-Paul; Wion, Didier

2014-04-26

Multipotent mesenchymal stromal cells (MSC), have the potential to differentiate into cells of the mesenchymal lineage and have non-progenitor functions including immunomodulation. The demonstration that MSCs are perivascular cells found in almost all adult tissues raises fascinating perspectives on their role in tissue maintenance and repair. However, some controversies about the physiological role of the perivascular MSCs residing outside the bone marrow and on their therapeutic potential in regenerative medicine exist. In brain, perivascular MSCs like pericytes and adventitial cells, could constitute another stem cell population distinct to the neural stem cell pool. The demonstration of the neuronal potential of MSCs requires stringent criteria including morphological changes, the demonstration of neural biomarkers expression, electrophysiological recordings, and the absence of cell fusion. The recent finding that brain cancer stem cells can transdifferentiate into pericytes is another facet of the plasticity of these cells. It suggests that the perversion of the stem cell potential of pericytes might play an even unsuspected role in cancer formation and tumor progression.

Brain mesenchymal stem cells: The other stem cells of the brain?

PubMed Central

Appaix, Florence; Nissou, Marie-France; van der Sanden, Boudewijn; Dreyfus, Matthieu; Berger, François; Issartel, Jean-Paul; Wion, Didier

2014-01-01

Multipotent mesenchymal stromal cells (MSC), have the potential to differentiate into cells of the mesenchymal lineage and have non-progenitor functions including immunomodulation. The demonstration that MSCs are perivascular cells found in almost all adult tissues raises fascinating perspectives on their role in tissue maintenance and repair. However, some controversies about the physiological role of the perivascular MSCs residing outside the bone marrow and on their therapeutic potential in regenerative medicine exist. In brain, perivascular MSCs like pericytes and adventitial cells, could constitute another stem cell population distinct to the neural stem cell pool. The demonstration of the neuronal potential of MSCs requires stringent criteria including morphological changes, the demonstration of neural biomarkers expression, electrophysiological recordings, and the absence of cell fusion. The recent finding that brain cancer stem cells can transdifferentiate into pericytes is another facet of the plasticity of these cells. It suggests that the perversion of the stem cell potential of pericytes might play an even unsuspected role in cancer formation and tumor progression. PMID:24772240

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.

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.

Hyperpolarized xenon magnetic resonance of the lung and the brain

NASA Astrophysics Data System (ADS)

Venkatesh, Arvind Krishnamachari

2001-04-01

Hyperpolarized noble gas Magnetic Resonance Imaging (MRI) is a new diagnostic modality that has been used successfully for lung imaging. Xenon is soluble in blood and inhaled xenon is transported to the brain via circulating blood. Xenon also accumulates in the lipid rich white matter of the brain. Hyperpolarized xenon can hence be used as a tissue- sensitive probe of brain function. The goals of this study were to identify the NMR resonances of xenon in the rat brain and evaluate the role of hyperpolarized xenon for brain MRI. We have developed systems to produce sufficient volumes of hyperpolarized xenon for in vivo brain experiments. The specialized instrumentation developed include an apparatus for optical pump-cell manufacture and high purity gas manifolds for filling cells. A hyperpolarized gas delivery system was designed to ventilate small animals with hyperpolarized xenon for transport to the brain. The T1 of xenon dissolved in blood indicates that the lifetime of xenon in the blood is sufficient for significant magnetization to be transferred to distal tissues. A variety of carrier agents for intravenous delivery of hyperpolarized xenon were tested for transport to distal tissues. Using our new gas delivery system, high SNR 129Xe images of rat lungs were obtained. Spectroscopy with hyperpolarized xenon indicated that xenon was transported from the lungs to the blood and tissues with intact magnetization. After preliminary studies that indicated the feasibility for in vivo rat brain studies, experiments were performed with adult rats and young rats with different stages of white matter development. Both in vivo and in vitro experiments showed the prominence of one peak from xenon in the rat brain, which was assigned to brain lipids. Cerebral brain perfusion was calculated from the wash-out of the hyperpolarized xenon signal in the brain. An increase in brain perfusion during maturation was observed. These experiments showed that hyperpolarized xenon MRI can be used to develop unique approaches to studying white matter and gray matter in the brain. Some of the possible applications of hyperpolarized xenon MRI in the brain are clinical diagnosis of white matter diseases, functional MRI (fMRI) and measurement of cerebral blood perfusion.

Impact of wavefront distortion and scattering on 2-photon microscopy in mammalian brain tissue

PubMed Central

Chaigneau, Emmanuelle; Wright, Amanda J.; Poland, Simon P.; Girkin, John M.; Silver, R. Angus

2011-01-01

Two-photon (2P) microscopy is widely used in neuroscience, but the optical properties of brain tissue are poorly understood. We have investigated the effect of brain tissue on the 2P point spread function (PSF2P) by imaging fluorescent beads through living cortical slices. By combining this with measurements of the mean free path of the excitation light, adaptive optics and vector-based modeling that includes phase modulation and scattering, we show that tissue-induced wavefront distortions are the main determinant of enlargement and distortion of the PSF2P at intermediate imaging depths. Furthermore, they generate surrounding lobes that contain more than half of the 2P excitation. These effects reduce the resolution of fine structures and contrast and they, together with scattering, limit 2P excitation. Our results disentangle the contributions of scattering and wavefront distortion in shaping the cortical PSF2P, thereby providing a basis for improved 2P microscopy. PMID:22109156

Isolation of viable Neospora caninum from brains of wild gray wolves (Canis lupus).

PubMed

Dubey, J P; Jenkins, M C; Ferreira, L R; Choudhary, S; Verma, S K; Kwok, O C H; Fetterer, R; Butler, E; Carstensen, M

2014-03-17

Neospora caninum is a common cause of abortion in cattle worldwide. Canids, including the dog and the dingo (Canis familiaris), the coyote (Canis latrans), and the gray wolf (Canis lupus) are its definitive hosts that can excrete environmentally resistant oocysts in the environment, but also can act as intermediate hosts, harboring tissue stages of the parasite. In an attempt to isolate viable N. caninum from tissues of naturally infected wolves, brain and heart tissue from 109 wolves from Minnesota were bioassayed in mice. Viable N. caninum (NcWolfMn1, NcWolfMn2) was isolated from the brains of two wolves by bioassays in interferon gamma gene knockout mice. DNA obtained from culture-derived N. caninum tachyzoites of the two isolates were analyzed by N. caninum-specific Nc5 polymerase chain reaction and confirmed diagnosis. This is the first report of isolation of N. caninum from tissues of any wild canid host. Published by Elsevier B.V.

On the characterization of the heterogeneous mechanical response of human brain tissue.

PubMed

Forte, Antonio E; Gentleman, Stephen M; Dini, Daniele

2017-06-01

The mechanical characterization of brain tissue is a complex task that scientists have tried to accomplish for over 50 years. The results in the literature often differ by orders of magnitude because of the lack of a standard testing protocol. Different testing conditions (including humidity, temperature, strain rate), the methodology adopted, and the variety of the species analysed are all potential sources of discrepancies in the measurements. In this work, we present a rigorous experimental investigation on the mechanical properties of human brain, covering both grey and white matter. The influence of testing conditions is also shown and thoroughly discussed. The material characterization performed is finally adopted to provide inputs to a mathematical formulation suitable for numerical simulations of brain deformation during surgical procedures.

Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues

PubMed Central

2013-01-01

Background Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times. Results In each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the influence of an artificial deprivation protocol, we identified a subset of these transcripts as specifically sleep-enhanced or sleep-repressed by requiring that their expression also change over the course of unperturbed sleep. 3% and 6% of the assayed transcripts showed “sleep specific” changes in the lung and heart respectively. Sleep specific transcripts in these tissues demonstrated highly significant overlap and shared temporal dynamics. Markers of cellular stress and the unfolded protein response were reduced during sleep in both tissues. These results mirror previous findings in brain. Sleep-enhanced pathways reflected the unique metabolic functions of each tissue. Transcripts related to carbohydrate and sulfur metabolic processes were enhanced by sleep in the lung, and collectively favor buffering from oxidative stress. DNA repair and protein metabolism annotations were significantly enriched among the sleep-enhanced transcripts in the heart. Our results also suggest that sleep may provide a Zeitgeber, or synchronizing cue, in the lung as a large cluster of transcripts demonstrated systematic changes in inter-animal variability as a function of both sleep duration and circadian time. Conclusion Our data support the notion that the molecular consequences of sleep/wake behavioral state extend beyond the brain to include peripheral tissues. Sleep state induces a highly overlapping response in both heart and lung. We conclude that sleep enhances organ specific molecular functions and that it has a ubiquitous role in reducing cellular metabolic stress in both brain and peripheral tissues. Finally, our data suggest a novel role for sleep in synchronizing transcription in peripheral tissues. PMID:23721503

Fetal brain extracellular matrix boosts neuronal network formation in 3D bioengineered model of cortical brain tissue.

PubMed

Sood, Disha; Chwalek, Karolina; Stuntz, Emily; Pouli, Dimitra; Du, Chuang; Tang-Schomer, Min; Georgakoudi, Irene; Black, Lauren D; Kaplan, David L

2016-01-01

The extracellular matrix (ECM) constituting up to 20% of the organ volume is a significant component of the brain due to its instructive role in the compartmentalization of functional microdomains in every brain structure. The composition, quantity and structure of ECM changes dramatically during the development of an organism greatly contributing to the remarkably sophisticated architecture and function of the brain. Since fetal brain is highly plastic, we hypothesize that the fetal brain ECM may contain cues promoting neural growth and differentiation, highly desired in regenerative medicine. Thus, we studied the effect of brain-derived fetal and adult ECM complemented with matricellular proteins on cortical neurons using in vitro 3D bioengineered model of cortical brain tissue. The tested parameters included neuronal network density, cell viability, calcium signaling and electrophysiology. Both, adult and fetal brain ECM as well as matricellular proteins significantly improved neural network formation as compared to single component, collagen I matrix. Additionally, the brain ECM improved cell viability and lowered glutamate release. The fetal brain ECM induced superior neural network formation, calcium signaling and spontaneous spiking activity over adult brain ECM. This study highlights the difference in the neuroinductive properties of fetal and adult brain ECM and suggests that delineating the basis for this divergence may have implications for regenerative medicine.

Research on terahertz properties of rat brain tissue sections during dehydration

NASA Astrophysics Data System (ADS)

Cui, Gangqiang; Liang, Jianfeng; Zhao, Hongwei; Zhao, Xianghui; Chang, Chao

2018-01-01

Biological tissue sections are always kept in a system purged with dry nitrogen for the measurement of terahertz spectrum. However, the injected nitrogen will cause dehydration of tissue sections, which will affect the accuracy of spectrum measurement. In this paper, terahertz time-domain spectrometer is used to measure the terahertz spectra of rat brain tissue sections during dehydration. The changes of terahertz properties, including terahertz transmittance, refractive index and extinction coefficient during dehydration are also analyzed. The amplitudes of terahertz time-domain spectra increase gradually during the dehydration process. Besides, the terahertz properties show obvious changes during the dehydration process. All the results indicate that the injected dry nitrogen has a significant effect on the terahertz spectra and properties of tissue sections. This study contributes to further research and application of terahertz technology in biomedical field.

Hypothalamic vitamin D improves glucose homeostasis and reduces weight

USDA-ARS?s Scientific Manuscript database

Despite clear associations between vitamin D deficiency and obesity and/or type 2 diabetes, a causal relationship is not established. Vitamin D receptors (VDRs) are found within multiple tissues, including the brain. Given the importance of the brain in controlling both glucose levels and body weigh...

Cobalt-55 positron emission tomography in traumatic brain injury: a pilot study.

PubMed Central

Jansen, H M; van der Naalt, J; van Zomeren, A H; Paans, A M; Veenma-van der Duin, L; Hew, J M; Pruim, J; Minderhoud, J M; Korf, J

1996-01-01

Traumatic brain injury is usually assessed with the Glasgow coma scale (GCS), CT, or MRI. After such injury, the injured brain tissue is characterised by calcium mediated neuronal damage and inflammation. Positron emission tomography with the isotope cobalt-55 (Co-PET) as a calcium tracer enables imaging of affected tissue in traumatic brain injury. The aim was to determine whether additional information can be gained by Co-PET in the diagnosis of moderate traumatic brain injury and to assess any prognostic value of Co-PET. Five patients with recent moderately severe traumatic brain injury were studied. CT was performed on the day of admission, EEG within one week, and MRI and Co-PET within four weeks of injury. Clinical assessment included neurological examination, GCS, neuropsychological testing, and Glasgow outcome scale (GOS) after one year. Co-PET showed focal uptake that extended beyond the morphological abnormalities shown by MRI and CT, in brain regions that were actually diagnosed with EEG. Thus Co-PET is potentially useful for diagnostic localisation of both structural and functional abnormalities in moderate traumatic brain injury. Images PMID:8708661

Label-free imaging of brain and brain tumor specimens with combined two-photon excited fluorescence and second harmonic generation microscopy

NASA Astrophysics Data System (ADS)

Jiang, Liwei; Wang, Xingfu; Wu, Zanyi; Du, Huiping; Wang, Shu; Li, Lianhuang; Fang, Na; Lin, Peihua; Chen, Jianxin; Kang, Dezhi; Zhuo, Shuangmu

2017-10-01

Label-free imaging techniques are gaining acceptance within the medical imaging field, including brain imaging, because they have the potential to be applied to intraoperative in situ identifications of pathological conditions. In this paper, we describe the use of two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) microscopy in combination for the label-free detection of brain and brain tumor specimens; gliomas. Two independently detecting channels were chosen to subsequently collect TPEF/SHG signals from the specimen to increase TPEF/SHG image contrasts. Our results indicate that the combined TPEF/SHG microscopic techniques can provide similar rat brain structural information and produce a similar resolution like conventional H&E staining in neuropathology; including meninges, cerebral cortex, white-matter structure corpus callosum, choroid plexus, hippocampus, striatum, and cerebellar cortex. It can simultaneously detect infiltrating human brain tumor cells, the extracellular matrix collagen fiber of connective stroma within brain vessels and collagen depostion in tumor microenvironments. The nuclear-to-cytoplasmic ratio and collagen content can be extracted as quantitative indicators for differentiating brain gliomas from healthy brain tissues. With the development of two-photon fiberscopes and microendoscope probes and their clinical applications, the combined TPEF and SHG microcopy may become an important multimodal, nonlinear optical imaging approach for real-time intraoperative histological diagnostics of residual brain tumors. These occur in various brain regions during ongoing surgeries through the method of simultaneously identifying tumor cells, and the change of tumor microenvironments, without the need for the removal biopsies and without the need for tissue labelling or fluorescent markers.

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.

Large-scale Scanning Transmission Electron Microscopy (Nanotomy) of Healthy and Injured Zebrafish Brain.

PubMed

Kuipers, Jeroen; Kalicharan, Ruby D; Wolters, Anouk H G; van Ham, Tjakko J; Giepmans, Ben N G

2016-05-25

Large-scale 2D electron microscopy (EM), or nanotomy, is the tissue-wide application of nanoscale resolution electron microscopy. Others and we previously applied large scale EM to human skin pancreatic islets, tissue culture and whole zebrafish larvae(1-7). Here we describe a universally applicable method for tissue-scale scanning EM for unbiased detection of sub-cellular and molecular features. Nanotomy was applied to investigate the healthy and a neurodegenerative zebrafish brain. Our method is based on standardized EM sample preparation protocols: Fixation with glutaraldehyde and osmium, followed by epoxy-resin embedding, ultrathin sectioning and mounting of ultrathin-sections on one-hole grids, followed by post staining with uranyl and lead. Large-scale 2D EM mosaic images are acquired using a scanning EM connected to an external large area scan generator using scanning transmission EM (STEM). Large scale EM images are typically ~ 5 - 50 G pixels in size, and best viewed using zoomable HTML files, which can be opened in any web browser, similar to online geographical HTML maps. This method can be applied to (human) tissue, cross sections of whole animals as well as tissue culture(1-5). Here, zebrafish brains were analyzed in a non-invasive neuronal ablation model. We visualize within a single dataset tissue, cellular and subcellular changes which can be quantified in various cell types including neurons and microglia, the brain's macrophages. In addition, nanotomy facilitates the correlation of EM with light microscopy (CLEM)(8) on the same tissue, as large surface areas previously imaged using fluorescent microscopy, can subsequently be subjected to large area EM, resulting in the nano-anatomy (nanotomy) of tissues. In all, nanotomy allows unbiased detection of features at EM level in a tissue-wide quantifiable manner.

Large-scale Scanning Transmission Electron Microscopy (Nanotomy) of Healthy and Injured Zebrafish Brain

PubMed Central

Kuipers, Jeroen; Kalicharan, Ruby D.; Wolters, Anouk H. G.

2016-01-01

Large-scale 2D electron microscopy (EM), or nanotomy, is the tissue-wide application of nanoscale resolution electron microscopy. Others and we previously applied large scale EM to human skin pancreatic islets, tissue culture and whole zebrafish larvae1-7. Here we describe a universally applicable method for tissue-scale scanning EM for unbiased detection of sub-cellular and molecular features. Nanotomy was applied to investigate the healthy and a neurodegenerative zebrafish brain. Our method is based on standardized EM sample preparation protocols: Fixation with glutaraldehyde and osmium, followed by epoxy-resin embedding, ultrathin sectioning and mounting of ultrathin-sections on one-hole grids, followed by post staining with uranyl and lead. Large-scale 2D EM mosaic images are acquired using a scanning EM connected to an external large area scan generator using scanning transmission EM (STEM). Large scale EM images are typically ~ 5 - 50 G pixels in size, and best viewed using zoomable HTML files, which can be opened in any web browser, similar to online geographical HTML maps. This method can be applied to (human) tissue, cross sections of whole animals as well as tissue culture1-5. Here, zebrafish brains were analyzed in a non-invasive neuronal ablation model. We visualize within a single dataset tissue, cellular and subcellular changes which can be quantified in various cell types including neurons and microglia, the brain's macrophages. In addition, nanotomy facilitates the correlation of EM with light microscopy (CLEM)8 on the same tissue, as large surface areas previously imaged using fluorescent microscopy, can subsequently be subjected to large area EM, resulting in the nano-anatomy (nanotomy) of tissues. In all, nanotomy allows unbiased detection of features at EM level in a tissue-wide quantifiable manner. PMID:27285162

MR elastography of hydrocephalus

NASA Astrophysics Data System (ADS)

Pattison, Adam J.; Lollis, S. Scott; Perrinez, Phillip R.; Weaver, John B.; Paulsen, Keith D.

2009-02-01

Hydrocephalus occurs due to a blockage in the transmission of cerebrospinal fluid (CSF) in either the ventricles or subarachnoid space. Characteristics of this condition include increased intracranial pressure, which can result in neurologic deterioration [1]. Magnetic resonance elastography (MRE) is an imaging technique that estimates the mechanical properties of tissue in vivo. While some investigations of brain tissue have been performed using MRE [2,3,4,5], the effects due to changes in interstitial pressure and fluid content on the mechanical properties of the brain remain unknown. The purpose of this work is to assess the potential of MRE to differentiate between the reconstructed properties of normal and hydrocephalic brains. MRE data was acquired in 18 female feline subjects, 12 of which received kaolin injections resulting in an acute form of hydrocephalus. In each animal, four MRE scans were performed during the process including one pre-injection and three post-injection scans. The elastic parameters were obtained using a subzone-based reconstruction algorithm that solves Navier's equations for linearly elastic materials [6]. The remaining cats were used as controls, injected with saline instead of kaolin. To determine the state of hydrocephalus, ventricular volume was estimated from segmenting anatomical images. The mean ventricular volume of hydrocephalic cats significantly increased (P <~ 0.0001) between the first and second scans. The mean volume was not observed to increase (P >~ 0.5) for the control cats. Also, there was an observable increase in the recorded elastic shear modulus of brain tissue in the normal and hydrocephalic acquisitions. Results suggest that MRE is able to detect changes in the mechanical properties of brain tissue resulting from kaolin-induced hydrocephalus, indicating the need for further study.

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.

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

Role of Monocarboxylate Transporters in Drug Delivery to the Brain

PubMed Central

Vijay, Nisha; Morris, Marilyn E.

2014-01-01

Monocarboxylate transporters (MCTs) are known to mediate the transport of short chain monocarboxylates such as lactate, pyruvate and butyrate. Currently, fourteen members of this transporter family have been identified by sequence homology, of which only the first four members (MCT1- MCT4) have been shown to mediate the proton-linked transport of monocarboxylates. Another transporter family involved in the transport of endogenous monocarboxylates is the sodium coupled MCTs (SMCTs). These act as a symporter and are dependent on a sodium gradient for their functional activity. MCT1 is the predominant transporter among the MCT isoforms and is present in almost all tissues including kidney, intestine, liver, heart, skeletal muscle and brain. The various isoforms differ in terms of their substrate specificity and tissue localization. Due to the expression of these transporters in the kidney, intestine, and brain, they may play an important role in influencing drug disposition. Apart from endogenous short chain monocarboxylates, they also mediate the transport of exogenous drugs such as salicylic acid, valproic acid, and simvastatin acid. The influence of MCTs on drug pharmacokinetics has been extensively studied for γ-hydroxybutyrate (GHB) including distribution of this drug of abuse into the brain and the results will be summarized in this review. The physiological role of these transporters in the brain and their specific cellular localization within the brain will also be discussed. This review will also focus on utilization of MCTs as potential targets for drug delivery into the brain including their role in the treatment of malignant brain tumors. PMID:23789956

Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia

USDA-ARS?s Scientific Manuscript database

Cerebral ischemia is caused by an interruption of blood flow to the brain which generally leads to irreversible brain damage. Ischemic injury is associated with vascular leakage, inflammation, tissue injury, and cell death. Cellular changes associated with ischemia include impairment of metabolism, ...

Mapping pharmaceuticals in rat brain sections using MALDI imaging mass spectrometry.

PubMed

Hsieh, Yunsheng; Li, Fangbiao; Korfmacher, Walter A

2010-01-01

Matrix-assisted laser desorption/ionization-tandem mass spectrometric method (MALDI-MS/MS) has proven to be a reliable tool for direct measurement of the disposition of small molecules in animal tissue sections. As example, MALDI-MS/MS imaging system was employed for visualizing the spatial distribution of astemizole and its primary metabolite in rat brain tissues. Astemizole is a second-generation antihistamine, a block peripheral H1 receptor, which was introduced to provide comparable therapeutic benefit but was withdrawn in most countries due to toxicity risks. Astemizole was observed to be heterogeneously distributed to most parts of brain tissue slices including cortex, hippocampus, hypothalamic, thalamus, and ventricle regions while its major metabolite, desmethylastemizole, was only found around ventricle sites. We have shown that astemizole alone is likely to be responsible for the central nervous system (CNS) side effects when its exposures became elevated.

Bio-heat transfer model of deep brain stimulation-induced temperature changes

NASA Astrophysics Data System (ADS)

Elwassif, Maged M.; Kong, Qingjun; Vazquez, Maribel; Bikson, Marom

2006-12-01

There is a growing interest in the use of chronic deep brain stimulation (DBS) for the treatment of medically refractory movement disorders and other neurological and psychiatric conditions. Fundamental questions remain about the physiologic effects of DBS. Previous basic research studies have focused on the direct polarization of neuronal membranes by electrical stimulation. The goal of this paper is to provide information on the thermal effects of DBS using finite element models to investigate the magnitude and spatial distribution of DBS-induced temperature changes. The parameters investigated include stimulation waveform, lead selection, brain tissue electrical and thermal conductivities, blood perfusion, metabolic heat generation during the stimulation and lead thermal conductivity/heat dissipation through the electrode. Our results show that clinical DBS protocols will increase the temperature of surrounding tissue by up to 0.8 °C depending on stimulation/tissue parameters.

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.

Requirement for interleukin-1 to drive brain inflammation reveals tissue-specific mechanisms of innate immunity.

PubMed

Giles, James A; Greenhalgh, Andrew D; Davies, Claire L; Denes, Adam; Shaw, Tovah; Coutts, Graham; Rothwell, Nancy J; McColl, Barry W; Allan, Stuart M

2015-02-01

The immune system is implicated in a wide range of disorders affecting the brain and is, therefore, an attractive target for therapy. Interleukin-1 (IL-1) is a potent regulator of the innate immune system important for host defense but is also associated with injury and disease in the brain. Here, we show that IL-1 is a key mediator driving an innate immune response to inflammatory challenge in the mouse brain but is dispensable in extracerebral tissues including the lung and peritoneum. We also demonstrate that IL-1α is an important ligand contributing to the CNS dependence on IL-1 and that IL-1 derived from the CNS compartment (most likely microglia) is the major source driving this effect. These data reveal previously unknown tissue-specific requirements for IL-1 in driving innate immunity and suggest that IL-1-mediated inflammation in the brain could be selectively targeted without compromising systemic innate immune responses that are important for resistance to infection. This property could be exploited to mitigate injury- and disease-associated inflammation in the brain without increasing susceptibility to systemic infection, an important complication in several neurological disorders. © 2014 The Authors. European Journal of Immunology published by Wiley-VCH Verlag GmbH & Co. KGaA Weinheim.

Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment

PubMed Central

Irimia, Andrei; Goh, S.-Y. Matthew; Torgerson, Carinna M.; Stein, Nathan R.; Chambers, Micah C.; Vespa, Paul M.; Van Horn, John D.

2013-01-01

Objective To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Methods Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. Results We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Conclusion Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. PMID:24011495

Electroencephalographic inverse localization of brain activity in acute traumatic brain injury as a guide to surgery, monitoring and treatment.

PubMed

Irimia, Andrei; Goh, S-Y Matthew; Torgerson, Carinna M; Stein, Nathan R; Chambers, Micah C; Vespa, Paul M; Van Horn, John D

2013-10-01

To inverse-localize epileptiform cortical electrical activity recorded from severe traumatic brain injury (TBI) patients using electroencephalography (EEG). Three acute TBI cases were imaged using computed tomography (CT) and multimodal magnetic resonance imaging (MRI). Semi-automatic segmentation was performed to partition the complete TBI head into 25 distinct tissue types, including 6 tissue types accounting for pathology. Segmentations were employed to generate a finite element method model of the head, and EEG activity generators were modeled as dipolar currents distributed over the cortical surface. We demonstrate anatomically faithful localization of EEG generators responsible for epileptiform discharges in severe TBI. By accounting for injury-related tissue conductivity changes, our work offers the most realistic implementation currently available for the inverse estimation of cortical activity in TBI. Whereas standard localization techniques are available for electrical activity mapping in uninjured brains, they are rarely applied to acute TBI. Modern models of TBI-induced pathology can inform the localization of epileptogenic foci, improve surgical efficacy, contribute to the improvement of critical care monitoring and provide guidance for patient-tailored treatment. With approaches such as this, neurosurgeons and neurologists can study brain activity in acute TBI and obtain insights regarding injury effects upon brain metabolism and clinical outcome. Published by Elsevier B.V.

Soft-tissue reactions following irradiation of primary brain and pituitary tumors

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

Baglan, R.J.; Marks, J.E.

1981-04-01

One hundred and ninety-nine patients who received radiation therapy for a primary brain or pituitary tumor were studied for radiation-induced soft-tissue reactions of the cranium, scalp, ears and jaw. The frequency of these reactions was studied as a function of: the radiation dose 5 mm below the skin surface, dose distribution, field size and fraction size. Forty percent of patients had complete and permanent epilation, while 21% had some other soft-tissue complication, including: scalp swelling-6%, external otitis-6%, otitis media-5%, ear swelling-4%, etc. The frequency of soft-tissue reactions correlates directly with the radiation dose at 5 mm below the skin surface.more » Patients treated with small portals (<70 cm/sup 2/) had few soft-tissue reactions. The dose to superficial tissues, and hence the frequency of soft-tissue reactions can be reduced by: (1) using high-energy megavoltage beams; (2) using equal loading of beams; and (3) possibly avoiding the use of electron beams.« less

Assessing Metabolism and Injury in Acute Human Traumatic Brain Injury with Magnetic Resonance Spectroscopy: Current and Future Applications

PubMed Central

Stovell, Matthew G.; Yan, Jiun-Lin; Sleigh, Alison; Mada, Marius O.; Carpenter, T. Adrian; Hutchinson, Peter J. A.; Carpenter, Keri L. H.

2017-01-01

Traumatic brain injury (TBI) triggers a series of complex pathophysiological processes. These include abnormalities in brain energy metabolism; consequent to reduced tissue pO2 arising from ischemia or abnormal tissue oxygen diffusion, or due to a failure of mitochondrial function. In vivo magnetic resonance spectroscopy (MRS) allows non-invasive interrogation of brain tissue metabolism in patients with acute brain injury. Nuclei with “spin,” e.g., 1H, 31P, and 13C, are detectable using MRS and are found in metabolites at various stages of energy metabolism, possessing unique signatures due to their chemical shift or spin–spin interactions (J-coupling). The most commonly used clinical MRS technique, 1H MRS, uses the great abundance of hydrogen atoms within molecules in brain tissue. Spectra acquired with longer echo-times include N-acetylaspartate (NAA), creatine, and choline. NAA, a marker of neuronal mitochondrial activity related to adenosine triphosphate (ATP), is reported to be lower in patients with TBI than healthy controls, and the ratio of NAA/creatine at early time points may correlate with clinical outcome. 1H MRS acquired with shorter echo times produces a more complex spectrum, allowing detection of a wider range of metabolites.31 P MRS detects high-energy phosphate species, which are the end products of cellular respiration: ATP and phosphocreatine (PCr). ATP is the principal form of chemical energy in living organisms, and PCr is regarded as a readily mobilized reserve for its replenishment during periods of high utilization. The ratios of high-energy phosphates are thought to represent a balance between energy generation, reserve and use in the brain. In addition, the chemical shift difference between inorganic phosphate and PCr enables calculation of intracellular pH.13 C MRS detects the 13C isotope of carbon in brain metabolites. As the natural abundance of 13C is low (1.1%), 13C MRS is typically performed following administration of 13C-enriched substrates, which permits tracking of the metabolic fate of the infused 13C in the brain over time, and calculation of metabolic rates in a range of biochemical pathways, including glycolysis, the tricarboxylic acid cycle, and glutamate–glutamine cycling. The advent of new hyperpolarization techniques to transiently boost signal in 13C-enriched MRS in vivo studies shows promise in this field, and further developments are expected. PMID:28955291

Biochemical changes related to hypoxia during cerebral aneurysm surgery: combined microdialysis and tissue oxygen monitoring: case report.

PubMed

Hutchinson, P J; Al-Rawi, P G; O'Connell, M T; Gupta, A K; Pickard, J D; Kirkpatrick, P J

2000-01-01

The objective of this study was to monitor brain metabolism on-line during aneurysm surgery, by combining the use of a multiparameter (brain tissue oxygen, brain carbon dioxide, pH, and temperature) sensor with microdialysis (extracellular glucose, lactate, pyruvate, and glutamate). The case illustrates the potential value of these techniques by demonstrating the effects of adverse physiological events on brain metabolism and the ability to assist in both intraoperative and postoperative decision-making. A 41-year-old woman presented with a World Federation of Neurological Surgeons Grade I subarachnoid hemorrhage. Angiography revealed a basilar artery aneurysm that was not amenable to coiling, so the aneurysm was clipped. Before the craniotomy was performed, a multiparameter sensor and a microdialysis catheter were inserted to monitor brain metabolism. During the operation, the brain oxygen level decreased, in relation to biochemical changes, including the reduction of extracellular glucose and pyruvate and the elevation of lactate and glutamate. These changes were reversible. However, when the craniotomy was closed, a second decrease in brain oxygen occurred in association with brain swelling, which immediately prompted a postoperative computed tomographic scan. The scan demonstrated acute hydrocephalus, requiring external ventricular drainage. The patient made a full recovery. The monitoring techniques influenced clinical decision-making in the treatment of this patient. On-line measurement of brain tissue gases and extracellular chemistry has the potential to assist in the perioperative and postoperative management of patients undergoing complex cerebrovascular surgery and to establish the effects of intervention on brain homeostasis.

Military blast exposure, ageing and white matter integrity

PubMed Central

Trotter, Benjamin B.; Robinson, Meghan E.; Milberg, William P.; McGlinchey, Regina E.

2015-01-01

Mild traumatic brain injury, or concussion, is associated with a range of neural changes including altered white matter structure. There is emerging evidence that blast exposure—one of the most pervasive causes of casualties in the recent overseas conflicts in Iraq and Afghanistan—is accompanied by a range of neurobiological events that may result in pathological changes to brain structure and function that occur independently of overt concussion symptoms. The potential effects of brain injury due to blast exposure are of great concern as a history of mild traumatic brain injury has been identified as a risk factor for age-associated neurodegenerative disease. The present study used diffusion tensor imaging to investigate whether military-associated blast exposure influences the association between age and white matter tissue structure integrity in a large sample of veterans of the recent conflicts (n = 190 blast-exposed; 59 without exposure) between the ages of 19 and 62 years. Tract-based spatial statistics revealed a significant blast exposure × age interaction on diffusion parameters with blast-exposed individuals exhibiting a more rapid cross-sectional age trajectory towards reduced tissue integrity. Both distinct and overlapping voxel clusters demonstrating the interaction were observed among the examined diffusion contrast measures (e.g. fractional anisotropy and radial diffusivity). The regions showing the effect on fractional anisotropy included voxels both within and beyond the boundaries of the regions exhibiting a significant negative association between fractional anisotropy and age in the entire cohort. The regional effect was sensitive to the degree of blast exposure, suggesting a ‘dose-response’ relationship between the number of blast exposures and white matter integrity. Additionally, there was an age-independent negative association between fractional anisotropy and years since most severe blast exposure in a subset of the blast-exposed group, suggesting a specific influence of time since exposure on tissue structure, and this effect was also independent of post-traumatic stress symptoms. Overall, these data suggest that blast exposure may negatively affect brain-ageing trajectories at the microstructural tissue level. Additional work examining longitudinal changes in brain tissue integrity in individuals exposed to military blast forces will be an important future direction to the initial findings presented here. PMID:26033970

Comparison of seven optical clearing methods for mouse brain

NASA Astrophysics Data System (ADS)

Wan, Peng; Zhu, Jingtan; Yu, Tingting; Zhu, Dan

2018-02-01

Recently, a variety of tissue optical clearing techniques have been developed to reduce light scattering for imaging deeper and three-dimensional reconstruction of tissue structures. Combined with optical imaging techniques and diverse labeling methods, these clearing methods have significantly promoted the development of neuroscience. However, most of the protocols were proposed aiming for specific tissue type. Though there are some comparison results, the clearing methods covered are limited and the evaluation indices are lack of uniformity, which made it difficult to select a best-fit protocol for clearing in practical applications. Hence, it is necessary to systematically assess and compare these clearing methods. In this work, we evaluated the performance of seven typical clearing methods, including 3DISCO, uDISCO, SeeDB, ScaleS, ClearT2, CUBIC and PACT, on mouse brain samples. First, we compared the clearing capability on both brain slices and whole-brains by observing brain transparency. Further, we evaluated the fluorescence preservation and the increase of imaging depth. The results showed that 3DISCO, uDISCO and PACT posed excellent clearing capability on mouse brains, ScaleS and SeeDB rendered moderate transparency, while ClearT2 was the worst. Among those methods, ScaleS was the best on fluorescence preservation, and PACT achieved the highest increase of imaging depth. This study is expected to provide important reference for users in choosing most suitable brain optical clearing method.

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.

Quantitative analysis of transcranial and intraparenchymal light penetration in human cadaver brain tissue.

PubMed

Tedford, Clark E; DeLapp, Scott; Jacques, Steven; Anders, Juanita

2015-04-01

Photobiomodulation (PBM) also known as low-level light therapy has been used successfully for the treatment of injury and disease of the nervous system. The use of PBM to treat injury and diseases of the brain requires an in-depth understanding of light propagation through tissues including scalp, skull, meninges, and brain. This study investigated the light penetration gradients in the human cadaver brain using a Transcranial Laser System with a 30 mm diameter beam of 808 nm wavelength light. In addition, the wavelength-dependence of light scatter and absorbance in intraparenchymal brain tissue using 660, 808, and 940 nm wavelengths was investigated. Intact human cadaver heads (n = 8) were obtained for measurement of light propagation through the scalp/skull/meninges and into brain tissue. The cadaver heads were sectioned in either the transverse or mid-sagittal. The sectioned head was mounted into a cranial fixture with an 808 nm wavelength laser system illuminating the head from beneath with either pulsed-wave (PW) or continuous-wave (CW) laser light. A linear array of nine isotropic optical fibers on a 5 mm pitch was inserted into the brain tissue along the optical axis of the beam. Light collected from each fiber was delivered to a multichannel power meter. As the array was lowered into the tissue, the power from each probe was recorded at 5 mm increments until the inner aspect of the dura mater was reached. Intraparenchymal light penetration measurements were made by delivering a series of wavelengths (660, 808, and 940 nm) through a separate optical fiber within the array, which was offset from the array line by 5 mm. Local light penetration was determined and compared across the selected wavelengths. Unfixed cadaver brains provide good anatomical localization and reliable measurements of light scatter and penetration in the CNS tissues. Transcranial application of 808 nm wavelength light penetrated the scalp, skull, meninges, and brain to a depth of approximately 40 mm with an effective attenuation coefficient for the system of 2.22 cm(-1) . No differences were observed in the results between the PW and CW laser light. The intraparenchymal studies demonstrated less absorption and scattering for the 808 nm wavelength light compared to the 660 or 940 nm wavelengths. Transcranial light measurements of unfixed human cadaver brains allowed for determinations of light penetration variables. While unfixed human cadaver studies do not reflect all the conditions seen in the living condition, comparisons of light scatter and penetration and estimates of fluence levels can be used to establish further clinical dosing. The 808 nm wavelength light demonstrated superior CNS tissue penetration. © 2015 Wiley Periodicals, Inc.

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.

Iron biomineralization of brain tissue and neurodegenerative disorders

NASA Astrophysics Data System (ADS)

Mikhaylova (Mikhailova), Albina

The brain is an organ with a high concentration of iron in specific areas, particularly in the globus pallidus, the substantia nigra, and the red nucleus. In certain pathological states, such as iron overload disease and neurodegenerative disorders, a disturbed iron metabolism can lead to increased accumulation of iron not only in these areas, but also in the brain regions that are typically low in iron content. Recent studies of the physical and magnetic properties of metalloproteins, and in particular the discovery of biogenic magnetite in human brain tissue, have raised new questions about the role of biogenic iron formations in living organisms. Further investigations revealed the presence of magnetite-like crystalline structures in human ferritin, and indicated that released ferritin iron might act as promoter of oxidative damage to tissue, therefore contributing to pathogenesis of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. The purpose of this work was to examine the elemental composition and structure of iron deposits in normal brain tissue as well as tissue affected by neurodegenerative disorders. Employing the methods of X-ray microfocus fluorescence mapping, X-ray Absorption Near Edge Structure (XANES), X-ray Absorption Fine Structure spectroscopy (XAFS), and light and electron microscopic examinations allows one to obtain qualitative as well as quantitative data with respect to the cellular distribution and chemical state of iron at levels not detected previously. The described tissue preparation technique allows not only satisfactory XAS iron elemental imaging in situ but also multimodal examination with light and electron microscopes of the same samples. The developed protocol has assured consistent and reproducible results on relatively large sections of flat-embedded tissue. The resulting tissue samples were adequate for XAS examination as well as sufficiently well-preserved for future microscopy studies. The continued development of this technique should lead to major advances in mapping iron anomalies and the related chemical and structural information directly to cells and tissue structures in human brain tissue. At present this is done primarily by iron staining methods and any information on the relationship between iron distribution and cellular structures obtained this way is limited. Iron staining also offers no information on the specific compounds of iron that are present. This can be vitally important as the form of iron [including its oxidation state] in the human body can determine whether it plays a detrimental or beneficial role in neurophysiological processes.

A correlative optical microscopy and scanning electron microscopy approach to locating nanoparticles in brain tumors.

PubMed

Kempen, Paul J; Kircher, Moritz F; de la Zerda, Adam; Zavaleta, Cristina L; Jokerst, Jesse V; Mellinghoff, Ingo K; Gambhir, Sanjiv S; Sinclair, Robert

2015-01-01

The growing use of nanoparticles in biomedical applications, including cancer diagnosis and treatment, demands the capability to exactly locate them within complex biological systems. In this work a correlative optical and scanning electron microscopy technique was developed to locate and observe multi-modal gold core nanoparticle accumulation in brain tumor models. Entire brain sections from mice containing orthotopic brain tumors injected intravenously with nanoparticles were imaged using both optical microscopy to identify the brain tumor, and scanning electron microscopy to identify the individual nanoparticles. Gold-based nanoparticles were readily identified in the scanning electron microscope using backscattered electron imaging as bright spots against a darker background. This information was then correlated to determine the exact location of the nanoparticles within the brain tissue. The nanoparticles were located only in areas that contained tumor cells, and not in the surrounding healthy brain tissue. This correlative technique provides a powerful method to relate the macro- and micro-scale features visible in light microscopy with the nanoscale features resolvable in scanning electron microscopy. Copyright © 2014 Elsevier Ltd. All rights reserved.

ALE Meta-Analysis of Schizophrenics Performing the N-Back Task

NASA Astrophysics Data System (ADS)

Harrell, Zachary

2010-10-01

MRI/fMRI has already proven itself as a valuable tool in the diagnosis and treatment of many illnesses of the brain, including cognitive problems. By exploiting the differences in magnetic susceptibility between oxygenated and deoxygenated hemoglobin, fMRI can measure blood flow in various regions of interest within the brain. This can determine the level of brain activity in relation to motor or cognitive functions and provide a metric for tissue damage or illness symptoms. Structural imaging techniques have shown lesions or deficiencies in tissue volumes in schizophrenics corresponding to areas primarily in the frontal and temporal lobes. These areas are currently known to be involved in working memory and attention, which many schizophrenics have trouble with. The ALE (Activation Likelihood Estimation) Meta-Analysis is able to statistically determine the significance of brain area activations based on the post-hoc combination of multiple studies. This process is useful for giving a general model of brain function in relation to a particular task designed to engage the affected areas (such as working memory for the n-back task). The advantages of the ALE Meta-Analysis include elimination of single subject anomalies, elimination of false/extremely weak activations, and verification of function/location hypotheses.

Targeted delivery of growth factors in ischemic stroke animal models.

PubMed

Rhim, Taiyoun; Lee, Minhyung

2016-01-01

Ischemic stroke is caused by reduced blood supply and leads to loss of brain function. The reduced oxygen and nutrient supply stimulates various physiological responses, including induction of growth factors. Growth factors prevent neuronal cell death, promote neovascularization, and induce cell growth. However, the concentration of growth factors is not sufficient to recover brain function after the ischemic damage, suggesting that delivery of growth factors into the ischemic brain may be a useful treatment for ischemic stroke. In this review, various approaches for the delivery of growth factors to ischemic brain tissue are discussed, including local and targeting delivery systems. To develop growth factor therapy for ischemic stroke, important considerations should be taken into account. First, growth factors may have possible side effects. Thus, concentration of growth factors should be restricted to the ischemic tissues by local administration or targeted delivery. Second, the duration of growth factor therapy should be optimized. Growth factor proteins may be degraded too fast to have a high enough therapeutic effect. Therefore, delivery systems for controlled release or gene delivery may be useful. Third, the delivery systems to the brain should be optimized according to the delivery route.

Apparent isotropic electrical property for electrical brain stimulation (EBS) using magnetic resonance diffusion weighted imaging (MR-DWI)

NASA Astrophysics Data System (ADS)

Lee, Mun Bae; Kwon, Oh-In

2018-04-01

Electrical brain stimulation (EBS) is an invasive electrotherapy and technique used in brain neurological disorders through direct or indirect stimulation using a small electric current. EBS has relied on computational modeling to achieve optimal stimulation effects and investigate the internal activations. Magnetic resonance diffusion weighted imaging (DWI) is commonly useful for diagnosis and investigation of tissue functions in various organs. The apparent diffusion coefficient (ADC) measures the intensity of water diffusion within biological tissues using DWI. By measuring trace ADC and magnetic flux density induced by the EBS, we propose a method to extract electrical properties including the effective extracellular ion-concentration (EEIC) and the apparent isotropic conductivity without any auxiliary additional current injection. First, the internal current density due to EBS is recovered using the measured one component of magnetic flux density. We update the EEIC by introducing a repetitive scheme called the diffusion weighting J-substitution algorithm using the recovered current density and the trace ADC. To verify the proposed method, we study an anesthetized canine brain to visualize electrical properties including electrical current density, effective extracellular ion-concentration, and effective isotropic conductivity by applying electrical stimulation of the brain.

Selection of internal reference genes for normalization of quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis in the canine brain and other organs.

PubMed

Park, Sang-Je; Huh, Jae-Won; Kim, Young-Hyun; Lee, Sang-Rae; Kim, Sang-Hyun; Kim, Sun-Uk; Kim, Heui-Soo; Kim, Min Kyu; Chang, Kyu-Tae

2013-05-01

Quantitative reverse transcription polymerase chain reaction (qRT-PCR) is a specific and sensitive technique for quantifying gene expression. To analyze qRT-PCR data accurately, suitable reference genes that show consistent expression patterns across different tissues and experimental conditions should be selected. The objective of this study was to obtain the most stable reference genes in dogs, using samples from 13 different brain tissues and 10 other organs. 16 well-known candidate reference genes were analyzed by the geNorm, NormFinder, and BestKeeper programs. Brain tissues were derived from several different anatomical regions, including the forebrain, cerebrum, diencephalon, hindbrain, and metencephalon, and grouped accordingly. Combination of the three different analyses clearly indicated that the ideal reference genes are ribosomal protien S5 (RPS5) in whole brain, RPL8 and RPS5 in whole body tissues, RPS5 and RPS19 in the forebrain and cerebrum, RPL32 and RPS19 in the diencephalon, GAPDH and RPS19 in the hindbrain, and MRPS7 and RPL13A in the metencephalon. These genes were identified as ideal for the normalization of qRT-PCR results in the respective tissues. These findings indicate more suitable and stable reference genes for future studies of canine gene expression.

Congenital toxoplasmosis: continued parasite proliferation in the fetal brain despite maternal immunological control in other tissues.

PubMed

Ferguson, David J P; Bowker, Colene; Jeffery, Katie J M; Chamberlain, Paul; Squier, Waney

2013-01-01

Congenital toxoplasmosis is a serious condition but little is known of the natural history of parasite development and associated fetal tissue destruction. Two cases identified by ultrasound underwent induced abortion at 21 and 30 weeks' gestation. At autopsy, the placenta and fetal organs were examined by histology and immunocytochemistry employing anti-Toxoplasma stage-specific antibodies to confirm diagnosis and also provide information on the stage of parasite development. In both cases, maternal serology prior to termination showed both specific immunoglobulin M (IgM) and immunoglobulin G (IgG), whereas retrospective analysis of an earlier sample (12-14 weeks' gestation) showed only IgM reactivity consistent with infection occurring in the first trimester. The finding of a number of tissue cysts but few or no tachyzoites within the placenta and fetal adrenal and heart is characteristic of a chronic infection. However, in contrast, there were still areas of the fetal brain with large numbers of actively dividing, tissue-destructive tachyzoites. These observations show that continued parasite proliferation and tissue destruction can occur within the fetal brain even when there is a marked maternal immune response including maternal IgG. This finding strongly suggests that there may be benefits from treating cases of recently acquired congenital infection to destroy any remaining proliferating parasites located in immunologically protected sites such as the fetal brain.

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.

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

The effect of saponification on the mucopolysaccharides of the ground substance of the human brain: the relation to focal edema and multiple sclerosis.

PubMed

Feigin, I

1981-03-01

The acid mucopolysaccharides of brain tissues are disclosed by their metachromatic staining with toluidine blue following saponification with potassium hydroxide, presumably as a result of the liberation of acid groups previously esterified. Earlier histochemical studies had disclosed the presence of neutral mucopolysaccharides by staining with the periodic acid-Schiff technique, and such staining is intensified by prior saponification. Many biochemical studies have reported the presence of both acid and neutral mucopolysaccharides in brain tissues. Within the white matter following brain edema, the quantity of stained mucopolysaccharides is decreased in the plaques of multiple sclerosis and pontine myelinolysis, and in the lesions of diffuse sclerosis. All of these are characterized by myelin loss with relative preservation of axons. The known physiological effects of the mucopolysaccharides on the water content of normal tissues, and on the properties and diffusability of the increments of fluid that constitute edema, lead to the suggestion that edema may play a major role in the pathogenesis of the demyelinating diseases, including multiple sclerosis.

The Influence of Adipose Tissue on Brain Development, Cognition, and Risk of Neurodegenerative Disorders.

PubMed

Letra, Liliana; Santana, Isabel

2017-01-01

The brain is a highly metabolic organ and thus especially vulnerable to changes in peripheral metabolism, including those induced by obesity-associated adipose tissue dysfunction. In this context, it is likely that the development and maturation of neurocognitive circuits may also be affected and modulated by metabolic environmental factors, beginning in utero. It is currently recognized that maternal obesity, either pre-gestational or gestational, negatively influences fetal brain development and elevates the risk of cognitive impairment and neuropsychiatric disorders in the offspring. During infancy and adolescence, obesity remains a limiting factor for healthy neurodevelopment, especially affecting executive functions but also attention, visuospatial ability, and motor skills. In middle age, obesity seems to induce an accelerated brain aging and thus may increase the risk of age-related neurodegenerative diseases such as Alzheimer's disease. In this chapter we review and discuss experimental and clinical evidence focusing on the influence of adipose tissue dysfunction on neurodevelopment and cognition across lifespan, as well as some possible mechanistic links, namely the role of the most well studied adipokines.

Evaluation of a deep learning approach for the segmentation of brain tissues and white matter hyperintensities of presumed vascular origin in MRI.

PubMed

Moeskops, Pim; de Bresser, Jeroen; Kuijf, Hugo J; Mendrik, Adriënne M; Biessels, Geert Jan; Pluim, Josien P W; Išgum, Ivana

2018-01-01

Automatic segmentation of brain tissues and white matter hyperintensities of presumed vascular origin (WMH) in MRI of older patients is widely described in the literature. Although brain abnormalities and motion artefacts are common in this age group, most segmentation methods are not evaluated in a setting that includes these items. In the present study, our tissue segmentation method for brain MRI was extended and evaluated for additional WMH segmentation. Furthermore, our method was evaluated in two large cohorts with a realistic variation in brain abnormalities and motion artefacts. The method uses a multi-scale convolutional neural network with a T 1 -weighted image, a T 2 -weighted fluid attenuated inversion recovery (FLAIR) image and a T 1 -weighted inversion recovery (IR) image as input. The method automatically segments white matter (WM), cortical grey matter (cGM), basal ganglia and thalami (BGT), cerebellum (CB), brain stem (BS), lateral ventricular cerebrospinal fluid (lvCSF), peripheral cerebrospinal fluid (pCSF), and WMH. Our method was evaluated quantitatively with images publicly available from the MRBrainS13 challenge ( n  = 20), quantitatively and qualitatively in relatively healthy older subjects ( n  = 96), and qualitatively in patients from a memory clinic ( n  = 110). The method can accurately segment WMH (Overall Dice coefficient in the MRBrainS13 data of 0.67) without compromising performance for tissue segmentations (Overall Dice coefficients in the MRBrainS13 data of 0.87 for WM, 0.85 for cGM, 0.82 for BGT, 0.93 for CB, 0.92 for BS, 0.93 for lvCSF, 0.76 for pCSF). Furthermore, the automatic WMH volumes showed a high correlation with manual WMH volumes (Spearman's ρ  = 0.83 for relatively healthy older subjects). In both cohorts, our method produced reliable segmentations (as determined by a human observer) in most images (relatively healthy/memory clinic: tissues 88%/77% reliable, WMH 85%/84% reliable) despite various degrees of brain abnormalities and motion artefacts. In conclusion, this study shows that a convolutional neural network-based segmentation method can accurately segment brain tissues and WMH in MR images of older patients with varying degrees of brain abnormalities and motion artefacts.

GCR Transport in the Brain: Assessment of Self-Shielding, Columnar Damage, and Nuclear Reactions on Cell Inactivation Rates

NASA Technical Reports Server (NTRS)

Shavers, M. R.; Atwell, W.; Cucinotta, F. A.; Badhwar, G. D. (Technical Monitor)

1999-01-01

Radiation shield design is driven by the need to limit radiation risks while optimizing risk reduction with launch mass/expense penalties. Both limitation and optimization objectives require the development of accurate and complete means for evaluating the effectiveness of various shield materials and body-self shielding. For galactic cosmic rays (GCR), biophysical response models indicate that track structure effects lead to substantially different assessments of shielding effectiveness relative to assessments based on LET-dependent quality factors. Methods for assessing risk to the central nervous system (CNS) from heavy ions are poorly understood at this time. High-energy and charge (HZE) ion can produce tissue events resulting in damage to clusters of cells in a columnar fashion, especially for stopping heavy ions. Grahn (1973) and Todd (1986) have discussed a microlesion concept or model of stochastic tissue events in analyzing damage from HZE's. Some tissues, including the CNS, maybe sensitive to microlesion's or stochastic tissue events in a manner not illuminated by either conventional dosimetry or fluence-based risk factors. HZE ions may also produce important lateral damage to adjacent cells. Fluences of high-energy proton and alpha particles in the GCR are many times higher than HZE ions. Behind spacecraft and body self-shielding the ratio of protons, alpha particles, and neutrons to HZE ions increases several-fold from free-space values. Models of GCR damage behind shielding have placed large concern on the role of target fragments produced from tissue atoms. The self-shielding of the brain reduces the number of heavy ions reaching the interior regions by a large amount and the remaining light particle environment (protons, neutrons, deuterons. and alpha particles) may be the greatest concern. Tracks of high-energy proton produce nuclear reactions in tissue, which can deposit doses of more than 1 Gv within 5 - 10 cell layers. Information on rates of cell killing from GCR, including patterns of cell killing from single particle tracks. can provide useful information on expected differences between proton and HZE tracks and clinical experiences with photon irradiation. To model effects on cells in the brain, it is important that transport models accurately describe changes in the GCR due to interactions in the cranium and proximate tissues. We describe calculations of the attenuated GCR particle fluxes at three dose-points in the brain and associated patterns of cell killing using biophysical models. The effects of the brain self-shielding and bone-tissue interface of the skull in modulating the GCR environment are considered. For each brain dose-point, the mass distribution in the surrounding 4(pi) solid angle is characterized using the CAM model to trace 512 rays. The CAM model describes the self-shielding by converting the tissue distribution to mass-equivalent aluminum, and nominal values of spacecraft shielding is considered. Particle transport is performed with the proton, neutron, and heavy-ion transport code HZETRN with the nuclear fragmentation model QMSFRG. The distribution of cells killed along the path of individual GCR ions is modeled using in vitro cell inactivation data for cells with varying sensitivity. Monte Carlo simulations of arrays of inactivated cells are considered for protons and heavy ions and used to describe the absolute number of cell killing events of various magnitude in the brain from the GCR. Included are simulations of positions of inactivated cells from stopping heavy ions and nuclear stars produced by high-energy ions most importantly, protons and neutrons.

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

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.

Parenteral diclofenac infusion significantly decreases brain-tissue oxygen tension in patients with poor-grade aneurysmal subarachnoid hemorrhage

PubMed Central

2013-01-01

Introduction Diclofenac, a nonsteroidal antiinflammatory drug, is commonly used as antipyretic therapy in intensive care. The purpose of this study was to investigate the effects of parenteral diclofenac infusion on brain homeostasis, including brain-tissue oxygen tension (PbtO2) and brain metabolism after aneurysmal subarachnoid hemorrhage (aSAH). Methods We conducted a prospective, observational study with retrospective analysis of 21 consecutive aSAH patients with multimodal neuromonitoring. Cerebral perfusion pressure (CPP), mean arterial pressure (MAP), intracranial pressure (ICP), body temperature, and PbtO2 were analyzed after parenteral diclofenac infusion administered over a 34-minute period (20 to 45 IQR). Data are given as mean ± standard error of mean and median with interquartile range (IQR), as appropriate. Time-series data were analyzed by using a general linear model extended by generalized estimation equations (GEEs). Results One-hundred twenty-three interventions were analyzed. Body temperature decreased from 38.3°C ± 0.05°C by 0.8°C ± 0.06°C (P < 0.001). A 10% decrease in MAP and CPP (P < 0.001) necessitated an increase of vasopressors in 26% (n = 32), colloids in 33% (n = 41), and crystalloids in 5% (n = 7) of interventions. PbtO2 decreased by 13% from a baseline value of 28.1 ± 2.2 mm Hg, resulting in brain-tissue hypoxia (PbtO2 <20 mm Hg) in 38% (n = 8) of patients and 35% (n = 43) of interventions. PbtO2 <30 mm Hg before intervention was associated with brain-tissue hypoxia after parenteral diclofenac infusion (likelihood ratio, 40; AUC, 93%; 95% confidence interval (CI), 87% to 99%; P < 0.001). Cerebral metabolism showed no significant changes after parenteral diclofenac infusion. Conclusions Parenteral diclofenac infusion after aSAH effectively reduces body temperature, but may lead to CPP decrease and brain-tissue hypoxia, which were both associated with poor outcome after aSAH. PMID:23663770

Fiber-probe optical spectroscopy discriminates normal brain from focal cortical dysplasia in pediatric subjects

NASA Astrophysics Data System (ADS)

Anand, Suresh; Cicchi, Riccardo; Giordano, Flavio; Conti, Valerio; Buccoliero, Anna Maria; Guerrini, Renzo; Pavone, Francesco S.

2017-02-01

Focal cortical dysplasia (FCD) is an abnormality in the cerebral cortex that is caused by malformations during cortical development. Currently, magnetic resonance imaging (MRI) and electro-corticography (ECoG) are used for detecting FCD. On the downside, MRI is very much insensitive to small malformations in the brain, while ECoG is an invasive and time consuming procedure. Recently, optical techniques were widely exploited as a minimally invasive and quantitative approaches for disease diagnosis. These techniques include fluorescence and Raman spectroscopy. The aim of this investigation is to study the diagnostic performances of optical spectroscopy incorporating fluorescence (at 378 nm and 445 nm excitation wavelengths) and Raman spectroscopy (at 785 nm excitation) for the discrimination of FCD from normal brain in pediatric subjects. The study included 10 normal and 17 FCD tissue sites from 3 normal and 7 FCD samples. The emission spectra of FCD at 378 nm excitation wavelength presented a blue-shifted peak with respect to normal tissue. Prominent spectral differences between normal and FCD tissue were observed at 1298 cm-1, 1302 cm-1, 1445 cm-1 and 1660 cm-1 using Raman spectroscopy. Tissue classification models were developed using a multivariate statistical method, principal component analysis. This study demonstrates that a combined spectroscopic approach can provide a better diagnostic capability for classifying normal and FCD tissues. Further, the implementation of the technology within a fiber probe could open the way for in vivo diagnostics and intra-operative surgical guidance.

In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

PubMed Central

Weaver, John; Yang, Yirong; Purvis, Rebecca; Weatherwax, Theodore; Rosen, Gerald M.; Liu, Ke Jian

2014-01-01

Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O2 may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O2 is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO2 in vivo remains largely uncharacterized. This study investigated striatal tissue pO2 changes in male C57BL/6 mice (16–20g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO2 in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO2 was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO2 to 64%. More importantly, pO2 did not recover fully to control levels even 24 hrs after administration of a single dose of METH. and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO2 indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO2, which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults. PMID:24412707

Central insulin action in energy and glucose homeostasis.

PubMed

Plum, Leona; Belgardt, Bengt F; Brüning, Jens C

2006-07-01

Insulin has pleiotropic biological effects in virtually all tissues. However, the relevance of insulin signaling in peripheral tissues has been studied far more extensively than its role in the brain. An evolving body of evidence indicates that in the brain, insulin is involved in multiple regulatory mechanisms including neuronal survival, learning, and memory, as well as in regulation of energy homeostasis and reproductive endocrinology. Here we review insulin's role as a central homeostatic signal with regard to energy and glucose homeostasis and discuss the mechanisms by which insulin communicates information about the body's energy status to the brain. Particular emphasis is placed on the controversial current debate about the similarities and differences between hypothalamic insulin and leptin signaling at the molecular level.

In vivo imaging of spontaneous low-frequency oscillations in cerebral hemodynamics with a digital red-green-blue camera

NASA Astrophysics Data System (ADS)

Mustari, Afrina; Nakamura, Naoki; Nishidate, Izumi; Kawauchi, Satoko; Sato, Shunichi; Sato, Manabu; Kokobo, Yasuaki

2017-04-01

Nervous system relies on a continuous and adequate supply of blood flow, bringing the nutrients that it needs and removing the waste products of metabolism. Failure of these mechanisms is found in a number of devastating cerebral diseases, including stroke, vascular dementia, brain injury and trauma. Vasomotion which is the spontaneous low-frequency oscillation derived by the contraction and relaxation of arterioles and appears to be an intrinsic property of the cerebral vasculature, is important for monitoring the cerebral flow, tissue metabolism and health status of brain tissue. In the present study, we investigated a method to visualize the spontaneous low-frequency oscillation of cerebral blood volume based on the sequential RGB images of exposed brain.

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.

Mercury and selenium levels, and selenium:mercury molar ratios of brain, muscle and other tissues in bluefish (Pomatomus saltatrix) from New Jersey, USA

PubMed Central

Burger, Joanna; Jeitner, Christian; Donio, Mark; Pittfield, Taryn; Gochfeld, Michael

2015-01-01

A number of contaminants affect fish health, including mercury and selenium, and the selenium: mercury molar ratio. Recently the protective effects of selenium on methylmercury toxicity have been publicized, particularly for consumption of saltwater fish. Yet the relative ameliorating effects of selenium on toxicity within fish have not been examined, nor has the molar ratio in different tissues, (i.e. brain). We examined mercury and selenium levels in brain, kidney, liver, red and white muscle, and skin and scales in bluefish (Pomatomus saltatrix) from New Jersey to determine whether there were toxic levels of either metal, and we computed the selenium: mercury molar ratios by tissues. Total mercury averaged 0.32 ± 0.02 ppm wet weight in edible muscle and 0.09 ± 0.01 ppm in brain. Selenium concentration averaged 0.37 ± 0.03 in muscle and 0.36 ± 0.03 ppm in brain. There were significant differences in levels of mercury, selenium, and selenium: mercury molar ratios, among tissues. Mercury and selenium levels were correlated in kidney and skin/scales. Mercury levels were highest in kidney, intermediate in muscle and liver, and lowest in brain and skin/scales; selenium levels were also highest in kidney, intermediate in liver, and were an order of magnitude lower in the white muscle and brain. Mercury levels in muscle, kidney and skin/scales were positively correlated with fish size (length). Selenium levels in muscle, kidney and liver were positively correlated with fish length, but in brain; selenium levels were negatively correlated with fish length. The selenium: mercury molar ratio was negatively correlated with fish length for white muscle, liver, kidney, and brain, particularly for fish over 50 cm in length, suggesting that older fish experience less protective advantages of selenium against mercury toxicity than smaller fish, and that consumers of bluefish similarly receive less advantage from eating larger fish. PMID:23202378

Structural and molecular interrogation of intact biological systems

PubMed Central

Chung, Kwanghun; Wallace, Jenelle; Kim, Sung-Yon; Kalyanasundaram, Sandhiya; Andalman, Aaron S.; Davidson, Thomas J.; Mirzabekov, Julie J.; Zalocusky, Kelly A.; Mattis, Joanna; Denisin, Aleksandra K.; Pak, Sally; Bernstein, Hannah; Ramakrishnan, Charu; Grosenick, Logan; Gradinaru, Viviana; Deisseroth, Karl

2014-01-01

Obtaining high-resolution information from a complex system, while maintaining the global perspective needed to understand system function, represents a key challenge in biology. Here we address this challenge with a method (termed CLARITY) for the transformation of intact tissue into a nanoporous hydrogel-hybridized form (crosslinked to a three-dimensional network of hydrophilic polymers) that is fully assembled but optically transparent and macromolecule-permeable. Using mouse brains, we show intact-tissue imaging of long-range projections, local circuit wiring, cellular relationships, subcellular structures, protein complexes, nucleic acids and neurotransmitters. CLARITY also enables intact-tissue in situ hybridization, immunohistochemistry with multiple rounds of staining and de-staining in non-sectioned tissue, and antibody labelling throughout the intact adult mouse brain. Finally, we show that CLARITY enables fine structural analysis of clinical samples, including non-sectioned human tissue from a neuropsychiatric-disease setting, establishing a path for the transmutation of human tissue into a stable, intact and accessible form suitable for probing structural and molecular underpinnings of physiological function and disease. PMID:23575631

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.

Specific regions of the brain are capable of fructose metabolism.

PubMed

Oppelt, Sarah A; Zhang, Wanming; Tolan, Dean R

2017-02-15

High fructose consumption in the Western diet correlates with disease states such as obesity and metabolic syndrome complications, including type II diabetes, chronic kidney disease, and non-alcoholic fatty acid liver disease. Liver and kidneys are responsible for metabolism of 40-60% of ingested fructose, while the physiological fate of the remaining fructose remains poorly understood. The primary metabolic pathway for fructose includes the fructose-transporting solute-like carrier transport proteins 2a (SLC2a or GLUT), including GLUT5 and GLUT9, ketohexokinase (KHK), and aldolase. Bioinformatic analysis of gene expression encoding these proteins (glut5, glut9, khk, and aldoC, respectively) identifies other organs capable of this fructose metabolism. This analysis predicts brain, lymphoreticular tissue, placenta, and reproductive tissues as possible additional organs for fructose metabolism. While expression of these genes is highest in liver, the brain is predicted to have expression levels of these genes similar to kidney. RNA in situ hybridization of coronal slices of adult mouse brains validate the in silico expression of glut5, glut9, khk, and aldoC, and show expression across many regions of the brain, with the most notable expression in the cerebellum, hippocampus, cortex, and olfactory bulb. Dissected samples of these brain regions show KHK and aldolase enzyme activity 5-10 times the concentration of that in liver. Furthermore, rates of fructose oxidation in these brain regions are 15-150 times that of liver slices, confirming the bioinformatics prediction and in situ hybridization data. This suggests that previously unappreciated regions across the brain can use fructose, in addition to glucose, for energy production. Copyright © 2016 Elsevier B.V. All rights reserved.

Specific regions of the brain are capable of fructose metabolism

PubMed Central

Oppelt, Sarah A.; Zhang, Wanming; Tolan, Dean R.

2017-01-01

High fructose consumption in the Western diet correlates with disease states such as obesity and metabolic syndrome complications, including type II diabetes, chronic kidney disease, and nonalcoholic fatty acid liver disease. Liver and kidneys are responsible for metabolism of 40–60% of ingested fructose, while the physiological fate of the remaining fructose remains poorly understood. The primary metabolic pathway for fructose includes the fructose-transporting solute-like carrier transport proteins 2a (SLC2a or GLUT), including GLUT5 and GLUT9, ketohexokinase (KHK), and aldolase. Bioinformatic analysis of gene expression encoding these proteins (glut5, glut9, khk, and aldoC, respectively) identifies other organs capable of this fructose metabolism. This analysis predicts brain, lymphoreticular tissue, placenta, and reproductive tissues as possible additional organs for fructose metabolism. While expression of these genes is highest in liver, the brain is predicted to have expression levels of these genes similar to kidney. RNA in situ hybridization of coronal slices of adult mouse brains validate the in silico expression of glut5, glut9, khk, and aldoC, and show expression across many regions of the brain, with the most notable expression in the cerebellum, hippocampus, cortex, and olfactory bulb. Dissected samples of these brain regions show KHK and aldolase enzyme activity 5–10 times the concentration of that in liver. Furthermore, rates of fructose oxidation in these brain regions are 15–150 times that of liver slices, confirming the bioinformatics prediction and in situ hybridization data. This suggests that previously unappreciated regions across the brain can use fructose, in addition to glucose, for energy production. PMID:28034722

Neurosteroids in hepatic encephalopathy: Novel insights and new therapeutic opportunities.

PubMed

Butterworth, Roger F

2016-06-01

Hepatic encephalopathy (HE) is a serious neuropsychiatric disorder resulting from liver failure. Symptoms of HE include mild cognitive impairment, stupor and coma. Morphological changes to neuroglia (both astrocytes and microglia) occur in HE consisting of cytotoxic brain edema (astrocyte swelling) in acute liver failure and Alzheimer type-2 astrocytosis in cirrhosis. Visual-evoked responses in animals with liver failure and HE manifest striking similarities to those in animals treated with agonists of the GABA-A receptor complex. Neurosteroids are synthesized in brain following activation of translocator protein (TSPO), a mitochondrial neuroglial cholesterol-transporter protein. TSPO sites are activated in both animal models of HE as well as in autopsied brain tissue from HE patients. Activation of TSPO sites results in increased cholesterol transport into the mitochondrion followed by stimulation of a metabolic pathway culminating in the synthesis of allopregnanolone (ALLO) and tetrahydrodeoxycorticosterone (THDOC), neurosteroids with potent positive allosteric modulatory action on the GABA-A receptor complex. Concentrations of ALLO and THDOC in brain tissue from mice with HE resulting from toxic liver injury are sufficient to induce sedation in animals of the same species and significant increases in concentrations of ALLO have been reported in autopsied brain tissue from cirrhotic patients with HE leading to the proposal that "increased GABAergic tone" in HE results from that increased brain concentrations of this neurosteroid. Agents with the potential to decrease neurosteroid synthesis and/or prevent their modulatory actions on the GABA-A receptor complex may provide novel approaches to the management and treatment of HE. Such agents include indomethacin, benzodiazepine receptor inverse agonists and a novel series of compounds known as GABA-A receptor-modulating steroid antagonists (GAMSA). Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

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.

A new viewpoint: running a nonprofit brain bank as a business.

PubMed

Rademaker, Sonja H M; Huitinga, Inge

2018-01-01

It has become clear over the past decades that studying postmortem human brain tissue is one of the most effective ways to increase our knowledge of the pathogenesis and etiology of neuropathologic and psychiatric diseases. Many breakthroughs in neuroscience have depended on the availability of human brain tissue. However, the process of brain banking presents many different challenges, including the high cost that is associated with collecting the samples and with providing the diagnostics, storage, and distribution. Funding is generally from research and facility grants and donations but all are irregular, uncertain, and only cover the costs for a determined period of time. For professional brain banks with extensive prospective donor programs and that are open-access it can be very beneficial to draft a business plan to achieve long-term sustainability. Such a business plan should identify the interests of the stakeholders and address the implementation of cost efficiency and cost recovery systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Genetic compendium of 1511 human brains available through the UK Medical Research Council Brain Banks Network Resource.

PubMed

Keogh, Michael J; Wei, Wei; Wilson, Ian; Coxhead, Jon; Ryan, Sarah; Rollinson, Sara; Griffin, Helen; Kurzawa-Akanbi, Marzena; Santibanez-Koref, Mauro; Talbot, Kevin; Turner, Martin R; McKenzie, Chris-Anne; Troakes, Claire; Attems, Johannes; Smith, Colin; Al Sarraj, Safa; Morris, Chris M; Ansorge, Olaf; Pickering-Brown, Stuart; Ironside, James W; Chinnery, Patrick F

2017-01-01

Given the central role of genetic factors in the pathogenesis of common neurodegenerative disorders, it is critical that mechanistic studies in human tissue are interpreted in a genetically enlightened context. To address this, we performed exome sequencing and copy number variant analysis on 1511 frozen human brains with a diagnosis of Alzheimer's disease (AD, n = 289), frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS, n = 252), Creutzfeldt-Jakob disease (CJD, n = 239), Parkinson's disease (PD, n = 39), dementia with Lewy bodies (DLB, n = 58), other neurodegenerative, vascular, or neurogenetic disorders (n = 266), and controls with no significant neuropathology (n = 368). Genomic DNA was extracted from brain tissue in all cases before exome sequencing (Illumina Nextera 62 Mb capture) with variants called by FreeBayes; copy number variant (CNV) analysis (Illumina HumanOmniExpress-12 BeadChip); C9orf72 repeat expansion detection; and APOE genotyping. Established or likely pathogenic heterozygous, compound heterozygous, or homozygous variants, together with the C9orf72 hexanucleotide repeat expansions and a copy number gain of APP, were found in 61 brains. In addition to known risk alleles in 349 brains (23.9% of 1461 undergoing exome sequencing), we saw an association between rare variants in GRN and DLB. Rare CNVs were found in <1.5% of brains, including copy number gains of PRPH that were overrepresented in AD. Clinical, pathological, and genetic data are available, enabling the retrieval of specific frozen brains through the UK Medical Research Council Brain Banks Network. This allows direct access to pathological and control human brain tissue based on an individual's genetic architecture, thus enabling the functional validation of known genetic risk factors and potentially pathogenic alleles identified in future studies. © 2017 Keogh et al.; Published by Cold Spring Harbor Laboratory Press.

Brain tumor modeling: glioma growth and interaction with chemotherapy

NASA Astrophysics Data System (ADS)

Banaem, Hossein Y.; Ahmadian, Alireza; Saberi, Hooshangh; Daneshmehr, Alireza; Khodadad, Davood

2011-10-01

In last decade increasingly mathematical models of tumor growths have been studied, particularly on solid tumors which growth mainly caused by cellular proliferation. In this paper we propose a modified model to simulate the growth of gliomas in different stages. Glioma growth is modeled by a reaction-advection-diffusion. We begin with a model of untreated gliomas and continue with models of polyclonal glioma following chemotherapy. From relatively simple assumptions involving homogeneous brain tissue bounded by a few gross anatomical landmarks (ventricles and skull) the models have been expanded to include heterogeneous brain tissue with different motilities of glioma cells in grey and white matter. Tumor growth is characterized by a dangerous change in the control mechanisms, which normally maintain a balance between the rate of proliferation and the rate of apoptosis (controlled cell death). Result shows that this model closes to clinical finding and can simulate brain tumor behavior properly.

An additional k-means clustering step improves the biological features of WGCNA gene co-expression networks.

PubMed

Botía, Juan A; Vandrovcova, Jana; Forabosco, Paola; Guelfi, Sebastian; D'Sa, Karishma; Hardy, John; Lewis, Cathryn M; Ryten, Mina; Weale, Michael E

2017-04-12

Weighted Gene Co-expression Network Analysis (WGCNA) is a widely used R software package for the generation of gene co-expression networks (GCN). WGCNA generates both a GCN and a derived partitioning of clusters of genes (modules). We propose k-means clustering as an additional processing step to conventional WGCNA, which we have implemented in the R package km2gcn (k-means to gene co-expression network, https://github.com/juanbot/km2gcn ). We assessed our method on networks created from UKBEC data (10 different human brain tissues), on networks created from GTEx data (42 human tissues, including 13 brain tissues), and on simulated networks derived from GTEx data. We observed substantially improved module properties, including: (1) few or zero misplaced genes; (2) increased counts of replicable clusters in alternate tissues (x3.1 on average); (3) improved enrichment of Gene Ontology terms (seen in 48/52 GCNs) (4) improved cell type enrichment signals (seen in 21/23 brain GCNs); and (5) more accurate partitions in simulated data according to a range of similarity indices. The results obtained from our investigations indicate that our k-means method, applied as an adjunct to standard WGCNA, results in better network partitions. These improved partitions enable more fruitful downstream analyses, as gene modules are more biologically meaningful.

Development of a Plastic Embedding Method for Large-Volume and Fluorescent-Protein-Expressing Tissues

PubMed Central

Yang, Zhongqin; Hu, Bihe; Zhang, Yuhui; Luo, Qingming; Gong, Hui

2013-01-01

Fluorescent proteins serve as important biomarkers for visualizing both subcellular organelles in living cells and structural and functional details in large-volume tissues or organs. However, current techniques for plastic embedding are limited in their ability to preserve fluorescence while remaining suitable for micro-optical sectioning tomography of large-volume samples. In this study, we quantitatively evaluated the fluorescence preservation and penetration time of several commonly used resins in a Thy1-eYFP-H transgenic whole mouse brain, including glycol methacrylate (GMA), LR White, hydroxypropyl methacrylate (HPMA) and Unicryl. We found that HMPA embedding doubled the eYFP fluorescence intensity but required long durations of incubation for whole brain penetration. GMA, Unicryl and LR White each penetrated the brain rapidly but also led to variable quenching of eYFP fluorescence. Among the fast-penetrating resins, GMA preserved fluorescence better than LR White and Unicryl. We found that we could optimize the GMA formulation by reducing the polymerization temperature, removing 4-methoxyphenol and adjusting the pH of the resin solution to be alkaline. By optimizing the GMA formulation, we increased percentage of eYFP fluorescence preservation in GMA-embedded brains nearly two-fold. These results suggest that modified GMA is suitable for embedding large-volume tissues such as whole mouse brain and provide a novel approach for visualizing brain-wide networks. PMID:23577174

Ultrastructural and molecular confirmation of the development of Sarcocystis neurona tissue cysts in the central nervous system of southern sea otters (Enhydra lutris nereis).

PubMed

Miller, M A; Barr, B C; Nordhausen, R; James, E R; Magargal, S L; Murray, M; Conrad, P A; Toy-Choutka, S; Jessup, D A; Grigg, M E

2009-10-01

In 2004, three wild sea otters were diagnosed with putative Sarcocystis neurona-associated meningoencephalitis by histopathology and immunohistochemistry. Schizonts, free merozoites and tissue cysts were observed in the brains of all three infected animals. Tissue cysts walls from sea otter 1 (SO1) stained positively using anti-S. neurona polyclonal antiserum. However, positive staining does not preclude infection by closely related or cross-reactive tissue cyst-forming coccidian parasites. Two immature tissue cysts in the brain of SO1 were examined using transmission electron microscopy. Ultrastructural features included cyst walls with thin villous projections up to 1 microm long with tapered ends and a distinctive, electron-dense outer lining layer composed of linearly-arranged, semi-circular structures with a "hobnailed" surface contour. Small numbers of microtubules extended down through the villi into the underlying granular layer. Metrocytes were short and plump with an anterior apical complex, 22 sub-pellicular microtubules, numerous free ribosomes and no rhoptries. Some metrocytes appeared to be dividing, with two adjacent nuclear profiles. Collectively these ultrastructural features were compatible with developing protozoal cysts and were similar to prior descriptions of S. neurona tissue cysts. Panspecific 18S rDNA primers were utilized to identify protozoa infecting the brains of these otters and DNA amplification and additional sequencing at the ITS1 locus confirmed that all three otters were infected with S. neurona. No other Sarcocystis spp. were detected in the brains or skeletal muscles of these animals by immunohistochemistry or PCR. We believe this is the first ultrastructural and molecular confirmation of the development of S. neurona tissue cysts in the CNS of any animal.

Ultrastructural and molecular confirmation of the development of Sarcocystis neurona tissue cysts in the central nervous system of southern sea otters (Enhydra lutris nereis)

PubMed Central

Miller, M.A.; Barr, B.C.; Nordhausen, R.; James, E.R.; Magargal, S.L.; Murray, M.; Conrad, P.A.; Toy-Choutka, S.; Jessup, D.A.; Grigg, M.E.

2009-01-01

In 2004, three wild sea otters were diagnosed with putative Sarcocystis neurona-associated meningoencephalitis by histopathology and immunohistochemistry. Schizonts, free merozoites and tissue cysts were observed in the brains of all three infected animals. Tissue cysts from sea otter 1 (SO1) stained positively using anti-S. neurona polyclonal antiserum. However, positive staining does not preclude infection by closely related or cross-reactive tissue cyst-forming coccidian parasites. Two immature tissue cysts in the brain of SO1 were examined using transmission electron microscopy. Ultrastructural features included cyst walls with thin villous projections up to 1 μm long with tapered ends and a distinctive, electron-dense outer lining layer composed of linearly-arranged, semi-circular structures with a “hobnailed” surface contour. Small numbers of microtubules extended down through the villi into the underlying granular layer. Metrocytes were short and plump with an anterior apical complex, 22 subpellicular microtubules, numerous free ribosomes and no rhoptries. Some metrocytes appeared to be dividing, with two adjacent nuclear profiles. Collectively these ultrastructural features were compatible with developing protozoal cysts and were similar to prior descriptions of S. neurona tissue cysts. Panspecific 18S rDNA primers were utilized to identify protozoa infecting the brains of these otters and DNA amplification and additional sequencing at the ITS1 locus confirmed that all three otters were infected with S. neurona. No other Sarcocystis spp. were detected in the brains or skeletal muscles of these animals by immunohistochemistry or PCR. We believe this is the first ultrastructural and molecular confirmation of the development of S. neurona tissue cysts in the CNS of any animal. PMID:19527725

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.

Aging effects on DNA methylation modules in human brain and blood tissue

PubMed Central

2012-01-01

Background Several recent studies reported aging effects on DNA methylation levels of individual CpG dinucleotides. But it is not yet known whether aging-related consensus modules, in the form of clusters of correlated CpG markers, can be found that are present in multiple human tissues. Such a module could facilitate the understanding of aging effects on multiple tissues. Results We therefore employed weighted correlation network analysis of 2,442 Illumina DNA methylation arrays from brain and blood tissues, which enabled the identification of an age-related co-methylation module. Module preservation analysis confirmed that this module can also be found in diverse independent data sets. Biological evaluation showed that module membership is associated with Polycomb group target occupancy counts, CpG island status and autosomal chromosome location. Functional enrichment analysis revealed that the aging-related consensus module comprises genes that are involved in nervous system development, neuron differentiation and neurogenesis, and that it contains promoter CpGs of genes known to be down-regulated in early Alzheimer's disease. A comparison with a standard, non-module based meta-analysis revealed that selecting CpGs based on module membership leads to significantly increased gene ontology enrichment, thus demonstrating that studying aging effects via consensus network analysis enhances the biological insights gained. Conclusions Overall, our analysis revealed a robustly defined age-related co-methylation module that is present in multiple human tissues, including blood and brain. We conclude that blood is a promising surrogate for brain tissue when studying the effects of age on DNA methylation profiles. PMID:23034122

Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice.

PubMed

Douris, Nicholas; Stevanovic, Darko M; Fisher, Ffolliott M; Cisu, Theodore I; Chee, Melissa J; Nguyen, Ngoc L; Zarebidaki, Eleen; Adams, Andrew C; Kharitonenkov, Alexei; Flier, Jeffrey S; Bartness, Timothy J; Maratos-Flier, Eleftheria

2015-07-01

Fibroblast growth factor 21 (FGF21) has multiple metabolic actions, including the induction of browning in white adipose tissue. Although FGF21 stimulated browning results from a direct interaction between FGF21 and the adipocyte, browning is typically associated with activation of the sympathetic nervous system through cold exposure. We tested the hypothesis that FGF21 can act via the brain, to increase sympathetic activity and induce browning, independent of cell-autonomous actions. We administered FGF21 into the central nervous system via lateral ventricle infusion into male mice and found that the central treatment increased norepinephrine turnover in target tissues that include the inguinal white adipose tissue and brown adipose tissue. Central FGF21 stimulated browning as assessed by histology, expression of uncoupling protein 1, and the induction of gene expression associated with browning. These effects were markedly attenuated when mice were treated with a β-blocker. Additionally, neither centrally nor peripherally administered FGF21 initiated browning in mice lacking β-adrenoceptors, demonstrating that an intact adrenergic system is necessary for FGF21 action. These data indicate that FGF21 can signal in the brain to activate the sympathetic nervous system and induce adipose tissue thermogenesis.

3D variational brain tumor segmentation on a clustered feature set

NASA Astrophysics Data System (ADS)

Popuri, Karteek; Cobzas, Dana; Jagersand, Martin; Shah, Sirish L.; Murtha, Albert

2009-02-01

Tumor segmentation from MRI data is a particularly challenging and time consuming task. Tumors have a large diversity in shape and appearance with intensities overlapping the normal brain tissues. In addition, an expanding tumor can also deflect and deform nearby tissue. Our work addresses these last two difficult problems. We use the available MRI modalities (T1, T1c, T2) and their texture characteristics to construct a multi-dimensional feature set. Further, we extract clusters which provide a compact representation of the essential information in these features. The main idea in this paper is to incorporate these clustered features into the 3D variational segmentation framework. In contrast to the previous variational approaches, we propose a segmentation method that evolves the contour in a supervised fashion. The segmentation boundary is driven by the learned inside and outside region voxel probabilities in the cluster space. We incorporate prior knowledge about the normal brain tissue appearance, during the estimation of these region statistics. In particular, we use a Dirichlet prior that discourages the clusters in the ventricles to be in the tumor and hence better disambiguate the tumor from brain tissue. We show the performance of our method on real MRI scans. The experimental dataset includes MRI scans, from patients with difficult instances, with tumors that are inhomogeneous in appearance, small in size and in proximity to the major structures in the brain. Our method shows good results on these test cases.

Neuroprotection against Surgically-Induced Brain Injury

PubMed Central

Jadhav, Vikram; Solaroglu, Ihsan; Obenaus, Andre; Zhang, John H.

2007-01-01

Background Neurosurgical procedures are carried out routinely in health institutions across the world. A key issue to be considered during neurosurgical interventions is that there is always an element of inevitable brain injury that results from the procedure itself due to the unique nature of the nervous system. Brain tissue at the periphery of the operative site is at risk of injury by various means including incisions and direct trauma, electrocautery, hemorrhage, and retractor stretch. Methods/Results In the present review we will elaborate upon this surgically-induced brain injury and also present a novel animal model to study it. Additionally, we will summarize preliminary results obtained by pretreatment with PP1, a src tyrosine kinase inhibitor reported to have neuroprotective properties in in-vivo experimental studies. Any form of pretreatment to limit the damage to the susceptible functional brain tissue during neurosurgical procedures may have a significant impact on the patient recovery. Conclusion This brief review is intended to raise the question of ‘neuroprotection against surgically-induced brain injury’ in the neurosurgical scientific community and stimulate discussions. PMID:17210286

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.

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.

Bioimaging of metals in brain tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and metallomics.

PubMed

Becker, J Sabine; Matusch, Andreas; Palm, Christoph; Salber, Dagmar; Morton, Kathryn A; Becker, J Susanne

2010-02-01

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed and established as an emerging technique in the generation of quantitative images of metal distributions in thin tissue sections of brain samples (such as human, rat and mouse brain), with applications in research related to neurodegenerative disorders. A new analytical protocol is described which includes sample preparation by cryo-cutting of thin tissue sections and matrix-matched laboratory standards, mass spectrometric measurements, data acquisition, and quantitative analysis. Specific examples of the bioimaging of metal distributions in normal rodent brains are provided. Differences to the normal were assessed in a Parkinson's disease and a stroke brain model. Furthermore, changes during normal aging were studied. Powerful analytical techniques are also required for the determination and characterization of metal-containing proteins within a large pool of proteins, e.g., after denaturing or non-denaturing electrophoretic separation of proteins in one-dimensional and two-dimensional gels. LA-ICP-MS can be employed to detect metalloproteins in protein bands or spots separated after gel electrophoresis. MALDI-MS can then be used to identify specific metal-containing proteins in these bands or spots. The combination of these techniques is described in the second section.

Disease-Associated Prion Protein in Neural and Lymphoid Tissues of Mink (Mustela vison) Inoculated with Transmissible Mink Encephalopathy

PubMed Central

Schneider, D. A.; Harrington, R. D.; Zhuang, D.; Yan, H.; Truscott, T. C.; Dassanayake, R. P.; O'Rourke, K. I.

2012-01-01

Summary Transmissible spongiform encephalopathies (TSEs) are diagnosed by immunodetection of disease-associated prion protein (PrPd). The distribution of PrPd within the body varies with the time-course of infection and between species, during interspecies transmission, as well as with prion strain. Mink are susceptible to a form of TSE known as transmissible mink encephalopathy (TME), presumed to arise due to consumption of feed contaminated with a single prion strain of ruminant origin. After extended passage of TME isolates in hamsters, two strains emerge, HY and DY, each of which is associated with unique structural isoforms of PrPTME and of which only the HY strain is associated with accumulation of PrPTME in lymphoid tissues. Information on the structural nature and lymphoid accumulation of PrPTME in mink is limited. In this study, 13 mink were challenged by intracerebral inoculation using late passage TME inoculum after which brain and lymphoid tissues were collected at preclinical and clinical time points. The distribution and molecular nature of PrPTME was investigated by techniques including blotting of paraffin wax-embedded tissue and epitope mapping by western blotting. PrPTME was detected readily in the brain and retropharyngeal lymph node during preclinical infection with delayed progression of accumulation within other lymphoid tissues. For comparison, three mink were inoculated by the oral route and examined during clinical disease. Accumulation of PrPTME in these mink was greater and more widespread, including follicles of rectoanal mucosa-associated lymphoid tissue. Western blot analyses revealed that PrPTME accumulating in the brain of mink is structurally most similar to that accumulating in the brain of hamsters infected with the DY strain. Collectively, the results of extended passage in mink are consistent with the presence of only a single strain of TME, the DY strain, capable of inducing accumulation of PrPTME in the lymphoid tissues of mink but not in hamsters. Thus mink are a relevant animal model for further study of this unique strain, which ultimately may have been introduced through consumption of a TSE of ruminant origin. PMID:22595634

Comparison of excitation wavelengths for in vivo deep imaging of mouse brain

NASA Astrophysics Data System (ADS)

Wang, Mengran; Wu, Chunyan; Li, Bo; Xia, Fei; Sinefeld, David; Xu, Chris

2018-02-01

The attenuation of excitation power reaching the focus is the main issue that limits the depth penetration of highresolution imaging of biological tissue. The attenuation is caused by a combination of tissue scattering and absorption. Theoretical model of the effective attenuation length for in vivo mouse brain imaging has been built based on the data of the absorption of water and blood and the Mie scattering of a tissue-like phantom. Such a theoretical model has been corroborated at a number of excitation wavelengths, such as 800 nm, 1300 nm , and 1700 nm ; however, the attenuation caused by absorption is negligible when compared to tissue scattering at all these wavelength windows. Here we performed in vivo three-photon imaging of Texas Red-stained vasculature in the same mouse brain with different excitation wavelengths, 1700 nm, 1550 nm, 1500 nm and 1450 nm. In particular, our studies include the wavelength regime where strong water absorption is present (i.e., 1450 nm), and the attenuation by water absorption is predicted to be the dominant contribution in the excitation attenuation. Based on the experimental results, we found that the effective attenuation length at 1450 nm is significantly shorter than those at 1700 nm and 1300 nm. Our results confirm that the theoretical model based on tissue scattering and water absorption is accurate in predicting the effective attenuation lengths for in vivo imaging. The optimum excitation wavelength windows for in vivo mouse brain imaging are at 1300 nm and 1700 nm.

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.

First noninvasive thermal ablation of a brain tumor with MR-guided focused ultrasound

PubMed Central

2014-01-01

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) allows for precise thermal ablation of target tissues. While this emerging modality is increasingly used for the treatment of various types of extracranial soft tissue tumors, it has only recently been acknowledged as a modality for noninvasive neurosurgery. MRgFUS has been particularly successful for functional neurosurgery, whereas its clinical application for tumor neurosurgery has been delayed for various technical and procedural reasons. Here, we report the case of a 63-year-old patient presenting with a centrally located recurrent glioblastoma who was included in our ongoing clinical phase I study aimed at evaluating the feasibility and safety of transcranial MRgFUS for brain tumor ablation. Applying 25 high-power sonications under MR imaging guidance, partial tumor ablation could be achieved without provoking neurological deficits or other adverse effects in the patient. This proves, for the first time, the feasibility of using transcranial MR-guided focused ultrasound to safely ablate substantial volumes of brain tumor tissue. PMID:25671132

Optical Brain Imaging: A Powerful Tool for Neuroscience.

PubMed

Zhu, Xinpei; Xia, Yanfang; Wang, Xuecen; Si, Ke; Gong, Wei

2017-02-01

As the control center of organisms, the brain remains little understood due to its complexity. Taking advantage of imaging methods, scientists have found an accessible approach to unraveling the mystery of neuroscience. Among these methods, optical imaging techniques are widely used due to their high molecular specificity and single-molecule sensitivity. Here, we overview several optical imaging techniques in neuroscience of recent years, including brain clearing, the micro-optical sectioning tomography system, and deep tissue imaging.

Gadolinium Accumulation in the Deep Cerebellar Nuclei and Globus Pallidus After Exposure to Linear but Not Macrocyclic Gadolinium-Based Contrast Agents in a Retrospective Pig Study With High Similarity to Clinical Conditions.

PubMed

Boyken, Janina; Frenzel, Thomas; Lohrke, Jessica; Jost, Gregor; Pietsch, Hubertus

2018-05-01

The aim of this retrospective study was to determine the gadolinium (Gd) concentration in different brain areas in a pig cohort that received repeated administration of Gd-based contrast agents (GBCAs) at standard doses over several years, comparable with a clinical setting. Brain tissue was collected from 13 Göttingen mini pigs that had received repeated intravenous injections of gadopentetate dimeglumine (Gd-DTPA; Magnevist) and/or gadobutrol (Gadovist). The animals have been included in several preclinical imaging studies since 2008 and received cumulative Gd doses ranging from 7 to 129 mmol per animal over an extended period. Two animals with no history of administration of GBCA were included as controls. Brain autopsies were performed not earlier than 8 and not later than 38 months after the last GBCA application. Tissues from multiple brain areas including cerebellar and cerebral deep nuclei, cerebellar and cerebral cortex, and pons were analyzed for Gd using inductively coupled plasma mass spectrometry. Of the 13 animals, 8 received up to 48 injections of gadobutrol and Gd-DTPA and 5 received up to 29 injections of gadobutrol only. In animals that had received both Gd-DTPA and gadobutrol, a median (interquartile range) Gd concentration of 1.0 nmol/g tissue (0.44-1.42) was measured in the cerebellar nuclei and 0.53 nmol/g (0.29-0.62) in the globus pallidus. The Gd concentration in these areas in gadobutrol-only animals was 50-fold lower with median concentrations of 0.02 nmol/g (0.01-0.02) for cerebellar nuclei and 0.01 nmol/g (0.01-0.01) for globus pallidus and was comparable with control animals with no GBCA history. Accordingly, in animals that received both GBCAs, the amount of residual Gd correlated with the administered dose of Gd-DTPA (P ≤ 0.002) but not with the total Gd dose, consisting of Gd-DTPA and gadobutrol. The Gd concentration in cortical tissue and in the pons was very low (≤0.07 nmol/g tissue) in all animals analyzed. Multiple exposure to macrocyclic gadobutrol is not associated with Gd deposition in brain tissue of healthy pigs. A single additional administration of linear Gd-DTPA is sufficient for Gd accumulation in the nucleus dentatus and globus pallidus, underlining the importance of obtaining a complete GBCA history in clinical studies.

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

Potential protective effects of cannabidiol on neuroanatomical alterations in cannabis users and psychosis: a critical review.

PubMed

Hermann, Derik; Schneider, Miriam

2012-01-01

Cannabis use and the development of schizophrenic psychoses share a variety of similarities. Both start during late adolescence; go along with neuropsychological deficits, reduced activity, motivation deficits, and hallucinations suggesting impairment of similar brain structures. In cannabis heavy users diminished regional gray and white matter volume was reported. Similar alterations were observed in the large literature addressing structural abnormalities in schizophrenia. Furthermore, in cannabis using schizophrenic patients, these brain alterations were especially pronounced. Close relatives of schizophrenic patients showed greater cannabis-associated brain tissue loss than non-relatives indicating a genetically mediated particular sensitivity to brain tissue loss. Possible mechanisms for the induction of structural brain alterations are here discussed including impairments of neurogenesis, disturbance of endocannabinoids and diminished neuroplasticity. Especially direct THC effects (or via endocannabinoids) may mediate diminished glutamatergic neurotransmission usually driving neuroplasticity. Correspondingly, alterations of the kynurenic acid blocking NMDA receptors may contribute to brain structure alterations. However, different cannabis compounds may exert opposite effects on the neuroanatomical changes underlying psychosis. In particular, cannabidiol (CBD) was shown to prevent THC associated hippocampal volume loss in a small pilot study. This finding is further supported by several animal experiments supporting neuroprotective properties of CBD mainly via anti-oxidative effects, CB2 receptors or adenosine receptors. We will discuss here the mechanisms by which CBD may reduce brain volume loss, including antagonism of THC, interactions with endocannabinoids, and mechanisms that specifically underlie antipsychotic properties of CBD.

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.

Exploring the mechanical behavior of degrading swine neural tissue at low strain rates via the fractional Zener constitutive model.

PubMed

Bentil, Sarah A; Dupaix, Rebecca B

2014-02-01

The ability of the fractional Zener constitutive model to predict the behavior of postmortem swine brain tissue was examined in this work. Understanding tissue behavior attributed to degradation is invaluable in many fields such as the forensic sciences or cases where only cadaveric tissue is available. To understand how material properties change with postmortem age, the fractional Zener model was considered as it includes parameters to describe brain stiffness and also the parameter α, which quantifies the viscoelasticity of a material. The relationship between the viscoelasticity described by α and tissue degradation was examined by fitting the model to data collected in a previous study (Bentil, 2013). This previous study subjected swine neural tissue to in vitro unconfined compression tests using four postmortem age groups (<6h, 24h, 3 days, and 1 week). All samples were compressed to a strain level of 10% using two compressive rates: 1mm/min and 5mm/min. Statistical analysis was used as a tool to study the influence of the fractional Zener constants on factors such as tissue degradation and compressive rate. Application of the fractional Zener constitutive model to the experimental data showed that swine neural tissue becomes less stiff with increased postmortem age. The fractional Zener model was also able to capture the nonlinear viscoelastic features of the brain tissue at low strain rates. The results showed that the parameter α was better correlated with compressive rate than with postmortem age. © 2013 Published by Elsevier Ltd.

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.

Characterization of Cerebral White Matter Properties Using Quantitative Magnetic Resonance Imaging Stains

PubMed Central

Hurley, Samuel A.; Samsonov, Alexey A.; Adluru, Nagesh; Hosseinbor, Ameer Pasha; Mossahebi, Pouria; Tromp, Do P.M.; Zakszewski, Elizabeth; Field, Aaron S.

2011-01-01

Abstract The image contrast in magnetic resonance imaging (MRI) is highly sensitive to several mechanisms that are modulated by the properties of the tissue environment. The degree and type of contrast weighting may be viewed as image filters that accentuate specific tissue properties. Maps of quantitative measures of these mechanisms, akin to microstructural/environmental-specific tissue stains, may be generated to characterize the MRI and physiological properties of biological tissues. In this article, three quantitative MRI (qMRI) methods for characterizing white matter (WM) microstructural properties are reviewed. All of these measures measure complementary aspects of how water interacts with the tissue environment. Diffusion MRI, including diffusion tensor imaging, characterizes the diffusion of water in the tissues and is sensitive to the microstructural density, spacing, and orientational organization of tissue membranes, including myelin. Magnetization transfer imaging characterizes the amount and degree of magnetization exchange between free water and macromolecules like proteins found in the myelin bilayers. Relaxometry measures the MRI relaxation constants T1 and T2, which in WM have a component associated with the water trapped in the myelin bilayers. The conduction of signals between distant brain regions occurs primarily through myelinated WM tracts; thus, these methods are potential indicators of pathology and structural connectivity in the brain. This article provides an overview of the qMRI stain mechanisms, acquisition and analysis strategies, and applications for these qMRI stains. PMID:22432902

Raman molecular imaging of brain frozen tissue sections.

PubMed

Kast, Rachel E; Auner, Gregory W; Rosenblum, Mark L; Mikkelsen, Tom; Yurgelevic, Sally M; Raghunathan, Aditya; Poisson, Laila M; Kalkanis, Steven N

2014-10-01

Raman spectroscopy provides a molecular signature of the region being studied. It is ideal for neurosurgical applications because it is non-destructive, label-free, not impacted by water concentration, and can map an entire region of tissue. The objective of this paper is to demonstrate the meaningful spatial molecular information provided by Raman spectroscopy for identification of regions of normal brain, necrosis, diffusely infiltrating glioma and solid glioblastoma (GBM). Five frozen section tissues (1 normal, 1 necrotic, 1 GBM, and 2 infiltrating glioma) were mapped in their entirety using a 300-µm-square step size. Smaller regions of interest were also mapped using a 25-µm step size. The relative concentrations of relevant biomolecules were mapped across all tissues and compared with adjacent hematoxylin and eosin-stained sections, allowing identification of normal, GBM, and necrotic regions. Raman peaks and peak ratios mapped included 1003, 1313, 1431, 1585, and 1659 cm(-1). Tissue maps identified boundaries of grey and white matter, necrosis, GBM, and infiltrating tumor. Complementary information, including relative concentration of lipids, protein, nucleic acid, and hemoglobin, was presented in a manner which can be easily adapted for in vivo tissue mapping. Raman spectroscopy can successfully provide label-free imaging of tissue characteristics with high accuracy. It can be translated to a surgical or laboratory tool for rapid, non-destructive imaging of tumor margins.

Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations.

PubMed

Lax, Nichola Z; Alston, Charlotte L; Schon, Katherine; Park, Soo-Mi; Krishnakumar, Deepa; He, Langping; Falkous, Gavin; Ogilvy-Stuart, Amanda; Lees, Christoph; King, Rosalind H; Hargreaves, Iain P; Brown, Garry K; McFarland, Robert; Dean, Andrew F; Taylor, Robert W

2015-07-01

Autosomal recessive mutations in the RARS2 gene encoding the mitochondrial arginyl-transfer RNA synthetase cause infantile-onset myoencephalopathy pontocerebellar hypoplasia type 6 (PCH6). We describe 2 sisters with novel compound heterozygous RARS2 mutations who presented perinatally with neurologic features typical of PCH6 but with additional features including cardiomyopathy, hydrops, and pulmonary hypoplasia and who died at 1 day and 14 days of age. Magnetic resonance imaging findings included marked cerebellar hypoplasia, gyral immaturity, punctate lesions in cerebral white matter, and unfused deep cerebral grey matter. Enzyme histochemistry of postmortem tissues revealed a near-global cytochrome c oxidase-deficiency; assessment of respiratory chain enzyme activities confirmed severe deficiencies involving complexes I, III, and IV. Molecular genetic studies revealed 2 RARS2 gene mutations: a c.1A>G, p.? variant predicted to abolish the initiator methionine, and a deep intronic c.613-3927C>T variant causing skipping of exons 6-8 in the mature RARS2 transcript. Neuropathologic investigation included low brain weights, small brainstem and cerebellum, deep cerebral white matter pathology, pontine nucleus neuron loss (in 1 sibling), and peripheral nerve pathology. Mitochondrial respiratory chain immunohistochemistry in brain tissues confirmed an absence of complexes I and IV immunoreactivity with sparing of mitochondrial numbers. These cases expand the clinical spectrum of RARS2 mutations, including antenatal features and widespread mitochondrial respiratory chain deficiencies in postmortem brain tissues.

Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations

PubMed Central

Lax, Nichola Z.; Alston, Charlotte L.; Schon, Katherine; Park, Soo-Mi; Krishnakumar, Deepa; He, Langping; Falkous, Gavin; Ogilvy-Stuart, Amanda; Lees, Christoph; King, Rosalind H.; Hargreaves, Iain P.; Brown, Garry K.; McFarland, Robert; Dean, Andrew F.; Taylor, Robert W.

2015-01-01

Abstract Autosomal recessive mutations in the RARS2 gene encoding the mitochondrial arginyl-transfer RNA synthetase cause infantile-onset myoencephalopathy pontocerebellar hypoplasia type 6 (PCH6). We describe 2 sisters with novel compound heterozygous RARS2 mutations who presented perinatally with neurologic features typical of PCH6 but with additional features including cardiomyopathy, hydrops, and pulmonary hypoplasia and who died at 1 day and 14 days of age. Magnetic resonance imaging findings included marked cerebellar hypoplasia, gyral immaturity, punctate lesions in cerebral white matter, and unfused deep cerebral grey matter. Enzyme histochemistry of postmortem tissues revealed a near-global cytochrome c oxidase-deficiency; assessment of respiratory chain enzyme activities confirmed severe deficiencies involving complexes I, III, and IV. Molecular genetic studies revealed 2 RARS2 gene mutations: a c.1A>G, p.? variant predicted to abolish the initiator methionine, and a deep intronic c.613-3927C>T variant causing skipping of exons 6–8 in the mature RARS2 transcript. Neuropathologic investigation included low brain weights, small brainstem and cerebellum, deep cerebral white matter pathology, pontine nucleus neuron loss (in 1 sibling), and peripheral nerve pathology. Mitochondrial respiratory chain immunohistochemistry in brain tissues confirmed an absence of complexes I and IV immunoreactivity with sparing of mitochondrial numbers. These cases expand the clinical spectrum of RARS2 mutations, including antenatal features and widespread mitochondrial respiratory chain deficiencies in postmortem brain tissues. PMID:26083569

Carbon Dioxide Fluctuations Are Associated with Changes in Cerebral Oxygenation and Electrical Activity in Infants Born Preterm.

PubMed

Dix, Laura Marie Louise; Weeke, Lauren Carleen; de Vries, Linda Simone; Groenendaal, Floris; Baerts, Willem; van Bel, Frank; Lemmers, Petra Maria Anna

2017-08-01

To evaluate the effects of acute arterial carbon dioxide partial pressure changes on cerebral oxygenation and electrical activity in infants born preterm. This retrospective observational study included ventilated infants born preterm with acute fluctuations of continuous end-tidal CO 2 (etCO 2 ) as a surrogate marker for arterial carbon dioxide partial pressure, during the first 72 hours of life. Regional cerebral oxygen saturation and fractional tissue oxygen extraction were monitored with near-infrared spectroscopy. Brain activity was monitored with 2-channel electroencephalography. Spontaneous activity transients (SATs) rate (SATs/minute) and interval between SATs (in seconds) were calculated. Ten-minute periods were selected for analysis: before, during, and after etCO 2 fluctuations of ≥5  mm Hg. Thirty-eight patients (mean ± SD gestational age of 29 ± 1.8 weeks) were included, with 60 episodes of etCO 2 increase and 70 episodes of etCO 2 decrease. During etCO 2 increases, brain oxygenation increased (regional cerebral oxygen saturation increased, fractional tissue oxygen extraction decreased; P < .01) and electrical activity decreased (SATs/minute decreased, interval between SATs increased; P < .01). All measures recovered when etCO 2 returned to baseline. During etCO 2 decreases, brain oxygenation decreased (regional cerebral oxygen saturation decreased, fractional tissue oxygen extraction decreased; P < .01) and brain activity increased (SATs/minute increased, P < .05), also with recovery after return of etCO 2 to baseline. An acute increase in etCO 2 is associated with increased cerebral oxygenation and decreased brain activity, whereas an acute decrease is associated with decreased cerebral oxygenation and slightly increased brain activity. Combining continuous CO 2 monitoring with near-infrared spectroscopy may enable the detection of otherwise undetected fluctuations in arterial carbon dioxide partial pressure that may be harmful to the neonatal brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Mathematical modeling of the malignancy of cancer using graph evolution.

PubMed

Gunduz-Demir, Cigdem

2007-10-01

We report a novel computational method based on graph evolution process to model the malignancy of brain cancer called glioma. In this work, we analyze the phases that a graph passes through during its evolution and demonstrate strong relation between the malignancy of cancer and the phase of its graph. From the photomicrographs of tissues, which are diagnosed as normal, low-grade cancerous and high-grade cancerous, we construct cell-graphs based on the locations of cells; we probabilistically generate an edge between every pair of cells depending on the Euclidean distance between them. For a cell-graph, we extract connectivity information including the properties of its connected components in order to analyze the phase of the cell-graph. Working with brain tissue samples surgically removed from 12 patients, we demonstrate that cell-graphs generated for different tissue types evolve differently and that they exhibit different phase properties, which distinguish a tissue type from another.

Reduced Leukocyte Infiltration in Absence of Eosinophils Correlates with Decreased Tissue Damage and Disease Susceptibility in ΔdblGATA Mice during Murine Neurocysticercosis.

PubMed

Mishra, Pramod K; Li, Qun; Munoz, Luis E; Mares, Chris A; Morris, Elizabeth G; Teale, Judy M; Cardona, Astrid E

2016-06-01

Neurocysticercosis (NCC) is one of the most common helminth parasitic diseases of the central nervous system (CNS) and the leading cause of acquired epilepsy worldwide. NCC is caused by the presence of the metacestode larvae of the tapeworm Taenia solium within brain tissues. NCC patients exhibit a long asymptomatic phase followed by a phase of symptoms including increased intra-cranial pressure and seizures. While the asymptomatic phase is attributed to the immunosuppressive capabilities of viable T. solium parasites, release of antigens by dying organisms induce strong immune responses and associated symptoms. Previous studies in T. solium-infected pigs have shown that the inflammatory response consists of various leukocyte populations including eosinophils, macrophages, and T cells among others. Because the role of eosinophils within the brain has not been investigated during NCC, we examined parasite burden, disease susceptibility and the composition of the inflammatory reaction in the brains of infected wild type (WT) and eosinophil-deficient mice (ΔdblGATA) using a murine model of NCC in which mice were infected intracranially with Mesocestoides corti, a cestode parasite related to T. solium. In WT mice, we observed a time-dependent induction of eosinophil recruitment in infected mice, contrasting with an overall reduced leukocyte infiltration in ΔdblGATA brains. Although, ΔdblGATA mice exhibited an increased parasite burden, reduced tissue damage and less disease susceptibility was observed when compared to infected WT mice. Cellular infiltrates in infected ΔdblGATA mice were comprised of more mast cells, and αβ T cells, which correlated with an abundant CD8+ T cell response and reduced CD4+ Th1 and Th2 responses. Thus, our data suggest that enhanced inflammatory response in WT mice appears detrimental and associates with increased disease susceptibility, despite the reduced parasite burden in the CNS. Overall reduced leukocyte infiltration due to absence of eosinophils correlates with attenuated tissue damage and longer survival of ΔdblGATA mice. Therefore, our study suggests that approaches to clear NCC will require strategies to tightly control the host immune response while eradicating the parasite with minimal damage to brain tissue.

Reduced Leukocyte Infiltration in Absence of Eosinophils Correlates with Decreased Tissue Damage and Disease Susceptibility in ΔdblGATA Mice during Murine Neurocysticercosis

PubMed Central

Mishra, Pramod K.; Li, Qun; Munoz, Luis E.; Mares, Chris A.; Morris, Elizabeth G.; Teale, Judy M.; Cardona, Astrid E.

2016-01-01

Neurocysticercosis (NCC) is one of the most common helminth parasitic diseases of the central nervous system (CNS) and the leading cause of acquired epilepsy worldwide. NCC is caused by the presence of the metacestode larvae of the tapeworm Taenia solium within brain tissues. NCC patients exhibit a long asymptomatic phase followed by a phase of symptoms including increased intra-cranial pressure and seizures. While the asymptomatic phase is attributed to the immunosuppressive capabilities of viable T. solium parasites, release of antigens by dying organisms induce strong immune responses and associated symptoms. Previous studies in T. solium-infected pigs have shown that the inflammatory response consists of various leukocyte populations including eosinophils, macrophages, and T cells among others. Because the role of eosinophils within the brain has not been investigated during NCC, we examined parasite burden, disease susceptibility and the composition of the inflammatory reaction in the brains of infected wild type (WT) and eosinophil-deficient mice (ΔdblGATA) using a murine model of NCC in which mice were infected intracranially with Mesocestoides corti, a cestode parasite related to T. solium. In WT mice, we observed a time-dependent induction of eosinophil recruitment in infected mice, contrasting with an overall reduced leukocyte infiltration in ΔdblGATA brains. Although, ΔdblGATA mice exhibited an increased parasite burden, reduced tissue damage and less disease susceptibility was observed when compared to infected WT mice. Cellular infiltrates in infected ΔdblGATA mice were comprised of more mast cells, and αβ T cells, which correlated with an abundant CD8+ T cell response and reduced CD4+ Th1 and Th2 responses. Thus, our data suggest that enhanced inflammatory response in WT mice appears detrimental and associates with increased disease susceptibility, despite the reduced parasite burden in the CNS. Overall reduced leukocyte infiltration due to absence of eosinophils correlates with attenuated tissue damage and longer survival of ΔdblGATA mice. Therefore, our study suggests that approaches to clear NCC will require strategies to tightly control the host immune response while eradicating the parasite with minimal damage to brain tissue. PMID:27332553

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.

Neurosteroid hydroxylase CYP7B: vivid reporter activity in dentate gyrus of gene-targeted mice and abolition of a widespread pathway of steroid and oxysterol hydroxylation.

PubMed

Rose, K; Allan, A; Gauldie, S; Stapleton, G; Dobbie, L; Dott, K; Martin, C; Wang, L; Hedlund, E; Seckl, J R; Gustafsson, J A; Lathe, R

2001-06-29

The major adrenal steroid dehydroepiandrosterone (DHEA) enhances memory and immune function but has no known dedicated receptor; local metabolism may govern its activity. We described a cytochrome P450 expressed in brain and other tissues, CYP7B, that catalyzes the 7alpha-hydroxylation of oxysterols and 3beta-hydroxysteroids including DHEA. We report here that CYP7B mRNA and 7alpha-hydroxylation activity are widespread in rat tissues. However, steroids related to DHEA are reported to be modified at positions other than 7alpha, exemplified by prominent 6alpha-hydroxylation of 5alpha-androstane-3beta,17beta-diol (A/anediol) in some rodent tissues including brain. To determine whether CYP7B is responsible for these and other activities we disrupted the mouse Cyp7b gene by targeted insertion of an IRES-lacZ reporter cassette, placing reporter enzyme activity (beta-galactosidase) under Cyp7b promoter control. In heterozygous mouse brain, chromogenic detection of reporter activity was strikingly restricted to the dentate gyrus. Staining did not exactly reproduce the in situ hybridization expression pattern; post-transcriptional control is inferred. Lower level staining was detected in cerebellum, liver, and kidney, and which largely paralleled mRNA distribution. Liver and kidney expression was sexually dimorphic. Mice homozygous for the insertion are viable and superficially normal, but ex vivo metabolism of DHEA to 7alpha-hydroxy-DHEA was abolished in brain, spleen, thymus, heart, lung, prostate, uterus, and mammary gland; lower abundance metabolites were also eliminated. 7alpha-Hydroxylation of 25-hydroxycholesterol and related substrates was also abolished, as was presumed 6alpha-hydroxylation of A/anediol. These different enzyme activities therefore derive from the Cyp7b gene. CYP7B is thus a major extrahepatic steroid and oxysterol hydroxylase and provides the predominant route for local metabolism of DHEA and related molecules in brain and other tissues.

Delayed brain radiation necrosis: pathological review and new molecular targets for treatment.

PubMed

Furuse, Motomasa; Nonoguchi, Naosuke; Kawabata, Shinji; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko

2015-12-01

Delayed radiation necrosis is a well-known adverse event following radiotherapy for brain diseases and has been studied since the 1930s. The primary pathogenesis is thought to be the direct damage to endothelial and glial cells, particularly oligodendrocytes, which causes vascular hyalinization and demyelination. This primary pathology leads to tissue inflammation and ischemia, inducing various tissue protective responses including angiogenesis. Macrophages and lymphocytes then infiltrate the surrounding areas of necrosis, releasing inflammatory cytokines such as interleukin (IL)-1α, IL-6, and tumor necrosis factor (TNF)-α. Microglia also express these inflammatory cytokines. Reactive astrocytes play an important role in angiogenesis, expressing vascular endothelial growth factor (VEGF). Some chemokine networks, like the CXCL12/CXCR4 axis, are upregulated by tissue inflammation. Hypoxia may mediate the cell-cell interactions among reactive astrocytes, macrophages, and microglial cells around the necrotic core. Recently, bevacizumab, an anti-VEGF antibody, has demonstrated promising results as an alternative treatment for radiation necrosis. The importance of VEGF in the pathophysiology of brain radiation necrosis is being recognized. The discovery of new molecular targets could facilitate novel treatments for radiation necrosis. This literature review will focus on recent work characterizing delayed radiation necrosis in the brain.

Differentiation of the seven major lyssavirus species by oligonucleotide microarray.

PubMed

Xi, Jin; Guo, Huancheng; Feng, Ye; Xu, Yunbin; Shao, Mingfu; Su, Nan; Wan, Jiayu; Li, Jiping; Tu, Changchun

2012-03-01

An oligonucleotide microarray, LyssaChip, has been developed and verified as a highly specific diagnostic tool for differentiation of the 7 major lyssavirus species. As with conventional typing microarray methods, the LyssaChip relies on sequence differences in the 371-nucleotide region coding for the nucleoprotein. This region was amplified using nested reverse transcription-PCR primers that bind to the 7 major lyssaviruses. The LyssaChip includes 57 pairs of species typing and corresponding control oligonucleotide probes (oligoprobes) immobilized on glass slides, and it can analyze 12 samples on a single slide within 8 h. Analysis of 111 clinical brain specimens (65 from animals with suspected rabies submitted to the laboratory and 46 of butchered dog brain tissues collected from restaurants) showed that the chip method was 100% sensitive and highly consistent with the "gold standard," a fluorescent antibody test (FAT). The chip method could detect rabies virus in highly decayed brain tissues, whereas the FAT did not, and therefore the chip test may be more applicable to highly decayed brain tissues than the FAT. LyssaChip may provide a convenient and inexpensive alternative for diagnosis and differentiation of rabies and rabies-related diseases.

On high b diffusion imaging in the human brain: ruminations and experimental insights.

PubMed

Mulkern, Robert V; Haker, Steven J; Maier, Stephan E

2009-10-01

Interest in the manner in which brain tissue signal decays with b factor in diffusion imaging schemes has grown in recent years following the observation that the decay curves depart from purely monoexponential decay behavior. Regardless of the model or fitting function proposed for characterizing sufficiently sampled decay curves (vide infra), the departure from monoexponentiality spells increased tissue characterization potential. The degree to which this potential can be harnessed to improve specificity, sensitivity and spatial localization of diseases in brain, and other tissues, largely remains to be explored. Furthermore, the degree to which currently popular diffusion tensor imaging methods, including visually impressive white matter fiber "tractography" results, have almost completely ignored the nonmonoexponential nature of the basic signal decay with b factor is worthy of communal introspection. Here we limit our attention to a review of the basic experimental features associated with brain water signal diffusion decay curves as measured over extended b-factor ranges, the simple few parameter fitting functions that have been proposed to characterize these decays and the more involved models, e.g.,"ruminations," which have been proposed to account for the nonmonoexponentiality to date.

On high b diffusion imaging in the human brain: ruminations and experimental insights✩

PubMed Central

Mulkern, Robert V.; Haker, Steven J.; Maier, Stephan E.

2010-01-01

Interest in the manner in which brain tissue signal decays with b factor in diffusion imaging schemes has grown in recent years following the observation that the decay curves depart from purely monoexponential decay behavior. Regardless of the model or fitting function proposed for characterizing sufficiently sampled decay curves (vide infra), the departure from monoexponentiality spells increased tissue characterization potential. The degree to which this potential can be harnessed to improve specificity, sensitivity and spatial localization of diseases in brain, and other tissues, largely remains to be explored. Furthermore, the degree to which currently popular diffusion tensor imaging methods, including visually impressive white matter fiber “tractography” results, have almost completely ignored the nonmonoexponential nature of the basic signal decay with b factor is worthy of communal introspection. Here we limit our attention to a review of the basic experimental features associated with brain water signal diffusion decay curves as measured over extended b-factor ranges, the simple few parameter fitting functions that have been proposed to characterize these decays and the more involved models, e.g.,“ruminations,” which have been proposed to account for the nonmonoexponentiality to date. PMID:19520535

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.

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.

Effect of naturally mouldy wheat or fungi administration on metallothioneins level in brain tissues of rats.

PubMed

Vasatkova, Anna; Krizova, Sarka; Krystofova, Olga; Adam, Vojtech; Zeman, Ladislav; Beklova, Miroslava; Kizek, Rene

2009-01-01

The aim of this study is to determine level of metallothioneins (MTs) in brain tissues of rats administered by feed mixtures with different content of mouldy wheat or fungi. Selected male laboratory rats of Wistar albino at age of 28 days were used in our experiments. The rats were administered by feed mixtures with different content of vitamins, naturally mouldy wheat or fungi for 28 days. At the very end of the experiment, the animals were put to death and brains were sampled. MT level was determined by differential pulse voltammetry Brdicka reaction. We found that MTs' level in brain tissues from rats administered by standard feed mixtures was significantly higher compared to the level of MTs in rats supplemented by vitamins. Further we studied the effect of supplementation of naturally mouldy wheat on MTs level in rats. In mouldy wheat we detected the presence of following fungi species: Mucor spp., Absidia spp., Penicillium spp., Aspergillus spp. and Fusarium spp. Moreover we also identified and quantified following mycotoxins - deoxynivalenol, zearalenone, T2-toxin and aflatoxins. Level of MTs determined in rats treated with 33 or 66% of mouldy wheat was significantly lower compared to control ones. On the other hand rats treated with 100% of mouldy wheat had less MTs but not significantly. Supplementation of vitamins to rats fed by mouldy wheat had adverse effect on MTs level compared to rats with no other supplementation by vitamins. Moreover vitamins supplementation has no effect on MTs level in brain tissues of rats treated or non-treated with Ganoderma lucidum L. Both mycotoxins and vitamins have considerable effect on level of MTs in brain tissues. It can be assumed that the administered substances markedly influence redox metabolism, which could negatively influence numerous biochemical pathways including those closely related with MTs.

Correlation between light scattering signal and tissue reversibility in rat brain exposed to hypoxia

NASA Astrophysics Data System (ADS)

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

2010-02-01

Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 +/- 15 s after starting nitrogen gas inhalation (mean +/- SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.

Tissue-specific concentrations and patterns of perfluoroalkyl carboxylates and sulfonates in East Greenland polar bears.

PubMed

Greaves, Alana K; Letcher, Robert J; Sonne, Christian; Dietz, Rune; Born, Erik W

2012-11-06

Several perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates (PFSAs) of varying chain length are bioaccumulative in biota. However, wildlife reports have focused on liver and with very little examination of other tissues, and thus there is a limited understanding of their distribution and potential effects in the mammalian body. In the present study, the comparative accumulation of C(6) to C(15) PFCAs, C(4), C(6), C(8) and C(10) PFSAs, and select precursors were examined in the liver, blood, muscle, adipose, and brain of 20 polar bears (Ursus maritimus) from Scoresby Sound, Central East Greenland. Overall, PFSA and PFCA concentrations were highest in liver followed by blood > brain > muscle ≈ adipose. Liver and blood samples contained proportionally more of the shorter/medium chain length (C(6) to C(11)) PFCAs, whereas adipose and brain samples were dominated by longer chain (C(13) to C(15)) PFCAs. PFCAs with lower lipophilicities accumulated more in the liver, whereas the brain accumulated PFCAs with higher lipophilicities. The concentration ratios (±SE) between perfluorooctane sulfonate and its precursor perfluorooctane sulfonamide varied among tissues from 9 (±1):1 (muscle) to 36 (±7):1 (liver). PFCA and PFSA patterns in polar bears indicate that the pharmacokinetics of these compounds are to some extent tissue-specific, and are the result of several factors that may include differing protein interactions throughout the body.

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.

Viral tropism and pathology associated with viral hemorrhagic septicemia in larval and juvenile Pacific herring

USGS Publications Warehouse

Lovy, Jan; Lewis, N.L.; Hershberger, P.K.; Bennett, W.; Meyers, T.R.; Garver, K.A.

2012-01-01

Viral hemorrhagic septicemia virus (VHSV) genotype IVa causes mass mortality in wild Pacific herring, a species of economic value, in the Northeast Pacific Ocean. Young of the year herring are particularly susceptible and can be carriers of the virus. To understand its pathogenesis, tissue and cellular tropisms of VHSV in larval and juvenile Pacific herring were investigated with immunohistochemistry, transmission electron microscopy, and viral tissue titer. In larval herring, early viral tropism for epithelial tissues (6d post-exposure) was indicated by foci of epidermal thickening that contained heavy concentrations of virus. This was followed by a cellular tropism for fibroblasts within the fin bases and the dermis, but expanded to cells of the kidney, liver, pancreas, gastrointestinal tract and meninges in the brain. Among wild juvenile herring that underwent a VHS epizootic in the laboratory, the disease was characterized by acute and chronic phases of death. Fish that died during the acute phase had systemic infections in tissues including the submucosa of the gastrointestinal tract, spleen, kidney, liver, and meninges. The disease then transitioned into a chronic phase that was characterized by the appearance of neurological signs including erratic and corkscrew swimming and darkening of the dorsal skin. During the chronic phase viral persistence occurred in nervous tissues including meninges and brain parenchymal cells and in one case in peripheral nerves, while virus was mostly cleared from the other tissues. The results demonstrate the varying VHSV tropisms dependent on the timing of infection and the importance of neural tissues for the persistence and perpetuation of chronic infections in Pacific herring.

The electroneutral sodium/bicarbonate cotransporter containing an amino terminal 123-amino-acid cassette is expressed predominantly in the heart

PubMed Central

Cooper, Deborah S.; Lee, Hye Jeong; Yang, Han Soo; Kippen, Joseph; Yun, C. Chris; Choi, Inyeong

2006-01-01

Summary In this study, we examined the tissue-specific expression of two electroneutral Na/HCO3 cotransporter (NBCn1) variants that differ from each other by the presence of the N-terminal 123 amino acids (cassette II). A rat Northern blot with the probe to nucleotides encoding cassette II detected a 9 kb NBCn1 mRNA strongly in the heart and weakly in skeletal muscles, but absent from most of the tissues including kidney, brain, and pancreas. In the rat heart, PCR with primers flanking cassette II preferentially amplified a DNA fragment that lacked cassette II. However, in the human heart, PCR preferentially amplified a fragment that contained cassette II. This larger PCR product was found virtually in all regions of the human cardiovascular system with strong amplification in the apex, atrium, and atrioventricular nodes. These findings indicate that the variant containing cassette II is almost absent in tissues including brain, kidney, and pancreas, where NBCn1 has been extensively examined. PMID:16547769

The roles of TAM receptor tyrosine kinases in the mammalian testis and immunoprivileged sites.

PubMed

Deng, Tingting; Chen, Qiaoyuan; Han, Daishu

2016-01-01

Three members of a receptor tyrosine kinase family, including Tyro3, Axl, and Mer, are collectively called as TAM receptors. TAM receptors have two common ligands, namely, growth arrest specific gene 6 (Gas6) and protein S (ProS). The TAM-Gas6/ProS system is essential for phagocytic removal of apoptotic cells, and plays critical roles in regulating immune response. Genetic studies have shown that TAM receptors are essential regulators of the tissue homeostasis in immunoprivileged sites, including the testis, retina and brain. The mechanisms by which the TAM-Gas6/ProS system regulates the tissue homeostasis in immunoprivileged sites are emerging. The roles of the TAM-Gas6/ProS system in regulating the immune privilege were intensively investigated in the mouse testis, and several studies were performed in the eye and brain. This review summarizes our current understanding of TAM signaling in the testis and other immunoprivileged tissues, as well as highlights topics that are worthy of further investigation.

Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke.

PubMed

Tatebayashi, Kotaro; Tanaka, Yasue; Nakano-Doi, Akiko; Sakuma, Rika; Kamachi, Saeko; Shirakawa, Manabu; Uchida, Kazutaka; Kageyama, Hiroto; Takagi, Toshinori; Yoshimura, Shinichi; Matsuyama, Tomohiro; Nakagomi, Takayuki

2017-06-01

Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.

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.

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.

Exercise Prevents Mental Illness

NASA Astrophysics Data System (ADS)

Purnomo, K. I.; Doewes, M.; Giri, M. K. W.; Setiawan, K. H.; Wibowo, I. P. A.

2017-03-01

Multiple current studies show that neuroinflammation may contribute to mental illness such as depression, anxiety, and mood disorder. Chronic inflammation in peripheral tissues is indicated by the increase of inflammatory marker like cytokine IL-6, TNF-α, and IL-1β. Pro-inflammatory cytokine in peripheral tissues can reach brain tissues and activate microglia and it causes neuroinflammation. Psychological stress may led peripheral and central inflammation. Activated microglia will produce pro-inflammatory cytokine, ROS, RNS, and tryptophan catabolizes. This neuroinflammation can promote metabolism changes of any neurotransmitter, such as serotonin, dopamine, and glutamate that will influence neurocircuit in the brain including basal ganglia and anterior cingulated cortex. It leads to mental illness. Exercise give contribution to reduce tissue inflammation. When muscle is contracting in an exercise, muscle will produce the secretion of cytokine like IL-6, IL-1ra, and IL-10. It will react as anti-inflammation and influence macrophage, T cell, monosit, protein Toll-Like Receptor (TLR), and then reduce neuroinflammation, characterised by the decrease of pro-inflammatory cytokine and prevent the activation of microglia in the brain. The objective of the present study is to review scientific articles in the literature related to the contribution of exercise to prevent and ease mental illness.

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.

Comparison of several oximes on reactivation of soman-inhibited blood, brain and tissue cholinesterase activity in rats

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

Shih, T.M.

1993-12-31

The ability of three oximes, HI-6, MMB-4 and ICD-467, to reactivate cholinesterase (ChE) inhibited by the organophosphorus compound soman was compared in blood (plasma and erythrocytes), brain regions (including spinal cord) and peripheral tissues of rats. Animals were intoxicated with soman (100 ttg/kg. SC; equivalent to 0.9 x LDs0 dose) and treated 1 min later with one of these oximes (100 or 200 ttmo1/kg, IM). Toxic sign scores and total tissue ChE activities were determined 30 min later. Soman markedly inhibited ChE activity in blood (93 - 96%), brain regions (ranging from 78% to 95%), and all peripheral tissues (rangingmore » from 48.9% to 99.8%) except liver (11.9%). In blood, treatment with HI-6 or ICD-467 resulted in significant reactivation of soman-inhibited ChE. in contrast, MMB-4 was completely ineffective. HI-6 and ICD-467 were equally effective at the high dose. At the low dose ICD-467 treatment resulted in significantly higher plasma ChE than Hl-6 treatment, whereas HI-6 treatment resulted in higher erythrocyte ChE than ICD-467 treatment. However, none of these three oximesreactivated or protected soman-inhibited ChE in the brain. In all peripheral tissues (except liver) studied, MMB-4 was not effective. 111-6 reactivated soman-inhibited ChE in all tis- sues except lung, heart, and skeletal muscle. ICD-467 was highly effective in reactivating ChE in all tissues and afforded a complete recovery of ChE to control levels in Intercostal muscle and salivary gland. Oxime treatments did not modify the toxic scores produced by soman.« 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.

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.

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.

Effects of ebselen on ischemia/reperfusion injury in rat brain.

PubMed

Aras, M; Altaş, M; Meydan, S; Nacar, E; Karcıoğlu, M; Ulutaş, K T; Serarslan, Y

2014-10-01

Interruption of blood flow may result in considerable tissue damage via ischemia/reperfusion (I/R) injury-induced oxidative stress in brain tissues. The aim of the present study was to investigate the effects of Ebselen treatment in short-term global brain I/R injury in rats. The study was carried out on 27 Wistar-albino rats, divided into three groups including Sham group (n = 11), I/R group (n = 8) and I/R+Ebselen group (n = 8). Malondialdehyde (MDA) levels were significantly increased in I/R group in comparison with the Sham group and I/R+Ebselen group (p < 0.001 and p < 0.01). Superoxide dismutase (SOD) activity was significantly lower in I/R group in comparison to both Sham (p < 0.001) and I/R+Ebselen (p < 0.01) groups. Similarly, SOD activity was decreased in I/R+Ebselen group when compared with Sham group (p < 0.001). Sham and I/R groups were similar in terms of nitric oxide (NO) levels. In contrast, the NO level was lower in I/R+Ebselen group when compared with Sham (p < 0.001) and I/R (p < 0.01) groups. There was no significant difference among the groups in terms of glutathione peroxidase and catalase activities. In histopathological examination, the brain tissues of rats that received Ebselen showed morphological improvement. Ebselen has neuron-protective effects due to its antioxidant properties as shown by the decrease in MDA overproduction, increase in SOD activity and the histological improvement after administration of Ebselen to I/R in brain tissue.

Aberrant expression of long noncoding RNAs in autistic brain.

PubMed

Ziats, Mark N; Rennert, Owen M

2013-03-01

The autism spectrum disorders (ASD) have a significant hereditary component, but the implicated genetic loci are heterogeneous and complex. Consequently, there is a gap in understanding how diverse genomic aberrations all result in one clinical ASD phenotype. Gene expression studies from autism brain tissue have demonstrated that aberrantly expressed protein-coding genes may converge onto common molecular pathways, potentially reconciling the strong heritability and shared clinical phenotypes with the genomic heterogeneity of the disorder. However, the regulation of gene expression is extremely complex and governed by many mechanisms, including noncoding RNAs. Yet no study in ASD brain tissue has assessed for changes in regulatory long noncoding RNAs (lncRNAs), which represent a large proportion of the human transcriptome, and actively modulate mRNA expression. To assess if aberrant expression of lncRNAs may play a role in the molecular pathogenesis of ASD, we profiled over 33,000 annotated lncRNAs and 30,000 mRNA transcripts from postmortem brain tissue of autistic and control prefrontal cortex and cerebellum by microarray. We detected over 200 differentially expressed lncRNAs in ASD, which were enriched for genomic regions containing genes related to neurodevelopment and psychiatric disease. Additionally, comparison of differences in expression of mRNAs between prefrontal cortex and cerebellum within individual donors showed ASD brains had more transcriptional homogeneity. Moreover, this was also true of the lncRNA transcriptome. Our results suggest that further investigation of lncRNA expression in autistic brain may further elucidate the molecular pathogenesis of this disorder.

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

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

Sawada, Y.; Kawai, R.; McManaway, M.

(3H)Cyclofoxy (CF: 17-cyclopropylmethyl-3,14-dihydroxy-4,5-alpha-epoxy-6-beta-fluoromorp hinan) is an opioid antagonist with affinity to both mu and kappa subtypes that was synthesized for quantitative evaluation of opioid receptor binding in vivo. Two sets of experiments in rats were analyzed. The first involved determining the metabolite-corrected blood concentration and tissue distribution of CF in brain 1 to 60 min after i.v. bolus injection. The second involved measuring brain washout for 15 to 120 s following intracarotid artery injection of CF. A physiologically based model and a classical compartmental pharmacokinetic model were compared. The models included different assumptions for transport across the blood-brain barrier (BBB);more » estimates of nonspecific tissue binding and specific binding to a single opiate receptor site were found to be essentially the same with both models. The nonspecific binding equilibrium constant varied modestly in different brain structures (Keq = 3-9), whereas the binding potential (BP) varied over a much broader range (BP = 0.6-32). In vivo estimates of the opioid receptor dissociation constant were similar for different brain structures (KD = 2.1-5.2 nM), whereas the apparent receptor density (Bmax) varied between 1 (cerebellum) and 78 (thalamus) pmol/g of brain. The receptor dissociation rate constants in cerebrum (k4 = 0.08-0.16 min-1; koff = 0.16-0.23 min-1) and brain vascular permeability (PS = 1.3-3.4 ml/min/g) are sufficiently high to achieve equilibrium conditions within a reasonable period of time. Graphical analysis of the data is inappropriate due to the high tissue-loss rate constant for CF in brain. From these findings, CF should be a very useful opioid receptor ligand for the estimation of the receptor binding parameters in human subjects using (18F)CF and positron emission tomography.« less

Quantitative imaging of magnesium distribution at single-cell resolution in brain tumors and infiltrating tumor cells with secondary ion mass spectrometry (SIMS)

PubMed Central

Chandra, Subhash; Parker, Dylan J.; Barth, Rolf F.; Pannullo, Susan C.

2016-01-01

Glioblastoma multiforme (GBM) is one of the deadliest forms of human brain tumors. The infiltrative pattern of growth of these tumors includes the spread of individual and/or clusters of tumor cells at some distance from the main tumor mass in parts of the brain protected by an intact blood-brain-barrier. Pathophysiological studies of GBM could be greatly enhanced by analytical techniques capable of in situ single-cell resolution measurements of infiltrating tumor cells. Magnesium homeostasis is an area of active investigation in high grade gliomas. In the present study, we have used the F98 rat glioma as a model of human GBM and an elemental/isotopic imaging technique of secondary ion mass spectrometry (SIMS), a CAMECA IMS-3f ion microscope, for studying Mg distributions with single-cell resolution in freeze-dried brain tissue cryosections. Quantitative observations were made on tumor cells in the main tumor mass, contiguous brain tissue, and infiltrating tumor cells in adjacent normal brain. The brain tissue contained a significantly lower total Mg concentration of 4.70 ± 0.93 mmol/Kg wet weight (mean ± SD) in comparison to 11.64 ± 1.96 mmol/Kg wet weight in tumor cells of the main tumor mass and 10.72 ± 1.76 mmol/Kg wet weight in infiltrating tumor cells (p<0.05). The nucleus of individual tumor cells contained elevated levels of bound Mg. These observations demonstrate enhanced Mg-influx and increased binding of Mg in tumor cells and provide strong support for further investigation of GBMs for altered Mg homeostasis and activation of Mg-transporting channels as possible therapeutic targets. PMID:26703785

Intraoperative Magnetic Resonance Imaging of Cerebral Oxygen Metabolism During Resection of Brain Lesions.

PubMed

Stadlbauer, Andreas; Merkel, Andreas; Zimmermann, Max; Sommer, Björn; Buchfelder, Michael; Meyer-Bäse, Anke; Rössler, Karl

2017-04-01

Tissue oxygen tension is an important parameter for brain tissue viability and its noninvasive intraoperative monitoring in the whole brain is of highly clinical relevance. The purpose of this study was the introduction of a multiparametric quantitative blood oxygenation dependent magnetic resonance imaging (MRI) approach for intraoperative examination of oxygen metabolism during the resection of brain lesions. Sixteen patients suffering from brain lesions were examined intraoperatively twice (before craniotomy and after gross-total resection) via the quantitative blood oxygenation dependent technique and a 1.5-Tesla MRI scanner, which is installed in an operating room. The MRI protocol included T2*- and T2 mapping and dynamic susceptibility weighted perfusion. Data analysis was performed with a custom-made, in-house MatLab software for calculation of maps of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) as well as of cerebral blood volume and cerebral blood flow. Perilesional edema showed a significant increase in both perfusion (cerebral blood volume +21%, cerebral blood flow +13%) and oxygen metabolism (OEF +32%, CMRO 2  +16%) after resection of the lesions. In perilesional nonedematous tissue only, however, oxygen metabolism (OEF +19%, CMRO 2  +11%) was significantly increased, but not perfusion. No changes were found in normal brain. Fortunately, no neurovascular adverse events were observed. This approach for intraoperative examination of oxygen metabolism in the whole brain is a new application of intraoperative MRI additionally to resection control (residual tumor detection) and updating of neuronavigation (brain shift detection). It may help to detect neurovascular adverse events early during surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Increased White Matter Inflammation in Aging- and Alzheimer's Disease Brain.

PubMed

Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R; Olah, Marta; Mantingh-Otter, Ietje J; Van Dam, Debby; De Deyn, Peter P; den Dunnen, Wilfred; Eggen, Bart J L; Amor, Sandra; Boddeke, Erik

2017-01-01

Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [ 11 C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration.

Nop2 is expressed during proliferation of neural stem cells and in adult mouse and human brain.

PubMed

Kosi, Nina; Alić, Ivan; Kolačević, Matea; Vrsaljko, Nina; Jovanov Milošević, Nataša; Sobol, Margarita; Philimonenko, Anatoly; Hozák, Pavel; Gajović, Srećko; Pochet, Roland; Mitrečić, Dinko

2015-02-09

The nucleolar protein 2 gene encodes a protein specific for the nucleolus. It is assumed that it plays a role in the synthesis of ribosomes and regulation of the cell cycle. Due to its link to cell proliferation, higher expression of Nop2 indicates a worse tumor prognosis. In this work we used Nop2(gt1gaj) gene trap mouse strain. While lethality of homozygous animals suggested a vital role of this gene, heterozygous animals allowed the detection of expression of Nop2 in various tissues, including mouse brain. Histochemistry, immunohistochemistry and immunoelectron microscopy techniques, applied to a mature mouse brain, human brain and on mouse neural stem cells revealed expression of Nop2 in differentiating cells, including astrocytes, as well as in mature neurons. Nop2 was detected in various regions of mouse and human brain, mostly in large pyramidal neurons. In the human, Nop2 was strongly expressed in supragranular and infragranular layers of the somatosensory cortex and in layer III of the cingulate cortex. Also, Nop2 was detected in CA1 and the subiculum of the hippocampus. Subcellular analyses revealed predominant location of Nop2 within the dense fibrillar component of the nucleolus. To test if Nop2 expression correlates to cell proliferation occurring during tissue regeneration, we induced strokes in mice by middle cerebral artery occlusion. Two weeks after stroke, the number of Nop2/nestin double positive cells in the region affected by ischemia and the periventricular zone substantially increased. Our findings suggest a newly discovered role of Nop2 in both mature neurons and in cells possibly involved in the regeneration of nervous tissue. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Decoding the non-coding genome: elucidating genetic risk outside the coding genome.

PubMed

Barr, C L; Misener, V L

2016-01-01

Current evidence emerging from genome-wide association studies indicates that the genetic underpinnings of complex traits are likely attributable to genetic variation that changes gene expression, rather than (or in combination with) variation that changes protein-coding sequences. This is particularly compelling with respect to psychiatric disorders, as genetic changes in regulatory regions may result in differential transcriptional responses to developmental cues and environmental/psychosocial stressors. Until recently, however, the link between transcriptional regulation and psychiatric genetic risk has been understudied. Multiple obstacles have contributed to the paucity of research in this area, including challenges in identifying the positions of remote (distal from the promoter) regulatory elements (e.g. enhancers) and their target genes and the underrepresentation of neural cell types and brain tissues in epigenome projects - the availability of high-quality brain tissues for epigenetic and transcriptome profiling, particularly for the adolescent and developing brain, has been limited. Further challenges have arisen in the prediction and testing of the functional impact of DNA variation with respect to multiple aspects of transcriptional control, including regulatory-element interaction (e.g. between enhancers and promoters), transcription factor binding and DNA methylation. Further, the brain has uncommon DNA-methylation marks with unique genomic distributions not found in other tissues - current evidence suggests the involvement of non-CG methylation and 5-hydroxymethylation in neurodevelopmental processes but much remains unknown. We review here knowledge gaps as well as both technological and resource obstacles that will need to be overcome in order to elucidate the involvement of brain-relevant gene-regulatory variants in genetic risk for psychiatric disorders. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads

PubMed Central

Lamers, Susanna L.; Rose, Rebecca; Maidji, Ekaterina; Agsalda-Garcia, Melissa; Nolan, David J.; Fogel, Gary B.; Salemi, Marco; Garcia, Debra L.; Bracci, Paige; Yong, William; Commins, Deborah; Said, Jonathan; Khanlou, Negar; Hinkin, Charles H.; Sueiras, Miguel Valdes; Mathisen, Glenn; Donovan, Suzanne; Shiramizu, Bruce; Stoddart, Cheryl A.; Singer, Elyse J.

2016-01-01

ABSTRACT HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV+) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis. IMPORTANCE It is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An ongoing question is, “Where is HIV hiding?” A well-studied HIV reservoir is “resting” T cells, which can be isolated from blood products and succumb to cART once activated. Less-studied reservoirs are anatomical tissue samples, which have unknown cART penetration, contain a comparably diverse spectrum of potentially HIV-infected immune cells, and are important since <2% of body lymphocytes actually reside in blood. We examined 229 varied autopsy specimens from 20 HIV+ participants who died while on cART and identified that >50% of tissues were HIV infected. Additionally, we identified considerable pathology in participants' tissues, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. This study substantiates that tissue-associated HIV is present despite cART and can inform future studies into HIV persistence. PMID:27466426

HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads.

PubMed

Lamers, Susanna L; Rose, Rebecca; Maidji, Ekaterina; Agsalda-Garcia, Melissa; Nolan, David J; Fogel, Gary B; Salemi, Marco; Garcia, Debra L; Bracci, Paige; Yong, William; Commins, Deborah; Said, Jonathan; Khanlou, Negar; Hinkin, Charles H; Sueiras, Miguel Valdes; Mathisen, Glenn; Donovan, Suzanne; Shiramizu, Bruce; Stoddart, Cheryl A; McGrath, Michael S; Singer, Elyse J

2016-10-15

HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV(+)) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis. It is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An ongoing question is, "Where is HIV hiding?" A well-studied HIV reservoir is "resting" T cells, which can be isolated from blood products and succumb to cART once activated. Less-studied reservoirs are anatomical tissue samples, which have unknown cART penetration, contain a comparably diverse spectrum of potentially HIV-infected immune cells, and are important since <2% of body lymphocytes actually reside in blood. We examined 229 varied autopsy specimens from 20 HIV(+) participants who died while on cART and identified that >50% of tissues were HIV infected. Additionally, we identified considerable pathology in participants' tissues, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. This study substantiates that tissue-associated HIV is present despite cART and can inform future studies into HIV persistence. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Recombinant Tissue Plasminogen Activator Induces Neurological Side Effects Independent on Thrombolysis in Mechanical Animal Models of Focal Cerebral Infarction: A Systematic Review and Meta-Analysis.

PubMed

Dong, Mei-Xue; Hu, Qing-Chuan; Shen, Peng; Pan, Jun-Xi; Wei, You-Dong; Liu, Yi-Yun; Ren, Yi-Fei; Liang, Zi-Hong; Wang, Hai-Yang; Zhao, Li-Bo; Xie, Peng

2016-01-01

Recombinant tissue plasminogen activator (rtPA) is the only effective drug approved by US FDA to treat ischemic stroke, and it contains pleiotropic effects besides thrombolysis. We performed a meta-analysis to clarify effect of tissue plasminogen activator (tPA) on cerebral infarction besides its thrombolysis property in mechanical animal stroke. Relevant studies were identified by two reviewers after searching online databases, including Pubmed, Embase, and ScienceDirect, from 1979 to 2016. We identified 6, 65, 17, 12, 16, 12 and 13 comparisons reporting effect of endogenous tPA on infarction volume and effects of rtPA on infarction volume, blood-brain barrier, brain edema, intracerebral hemorrhage, neurological function and mortality rate in all 47 included studies. Standardized mean differences for continuous measures and risk ratio for dichotomous measures were calculated to assess the effects of endogenous tPA and rtPA on cerebral infarction in animals. The quality of included studies was assessed using the Stroke Therapy Academic Industry Roundtable score. Subgroup analysis, meta-regression and sensitivity analysis were performed to explore sources of heterogeneity. Funnel plot, Trim and Fill method and Egger's test were obtained to detect publication bias. We found that both endogenous tPA and rtPA had not enlarged infarction volume, or deteriorated neurological function. However, rtPA would disrupt blood-brain barrier, aggravate brain edema, induce intracerebral hemorrhage and increase mortality rate. This meta-analysis reveals rtPA can lead to neurological side effects besides thrombolysis in mechanical animal stroke, which may account for clinical exacerbation for stroke patients that do not achieve vascular recanalization with rtPA.

Recombinant Tissue Plasminogen Activator Induces Neurological Side Effects Independent on Thrombolysis in Mechanical Animal Models of Focal Cerebral Infarction: A Systematic Review and Meta-Analysis

PubMed Central

Wei, You-Dong; Liu, Yi-Yun; Ren, Yi-Fei; Liang, Zi-Hong; Wang, Hai-Yang; Zhao, Li-Bo; Xie, Peng

2016-01-01

Background and Purpose Recombinant tissue plasminogen activator (rtPA) is the only effective drug approved by US FDA to treat ischemic stroke, and it contains pleiotropic effects besides thrombolysis. We performed a meta-analysis to clarify effect of tissue plasminogen activator (tPA) on cerebral infarction besides its thrombolysis property in mechanical animal stroke. Methods Relevant studies were identified by two reviewers after searching online databases, including Pubmed, Embase, and ScienceDirect, from 1979 to 2016. We identified 6, 65, 17, 12, 16, 12 and 13 comparisons reporting effect of endogenous tPA on infarction volume and effects of rtPA on infarction volume, blood-brain barrier, brain edema, intracerebral hemorrhage, neurological function and mortality rate in all 47 included studies. Standardized mean differences for continuous measures and risk ratio for dichotomous measures were calculated to assess the effects of endogenous tPA and rtPA on cerebral infarction in animals. The quality of included studies was assessed using the Stroke Therapy Academic Industry Roundtable score. Subgroup analysis, meta-regression and sensitivity analysis were performed to explore sources of heterogeneity. Funnel plot, Trim and Fill method and Egger’s test were obtained to detect publication bias. Results We found that both endogenous tPA and rtPA had not enlarged infarction volume, or deteriorated neurological function. However, rtPA would disrupt blood-brain barrier, aggravate brain edema, induce intracerebral hemorrhage and increase mortality rate. Conclusions This meta-analysis reveals rtPA can lead to neurological side effects besides thrombolysis in mechanical animal stroke, which may account for clinical exacerbation for stroke patients that do not achieve vascular recanalization with rtPA. PMID:27387385

3D brain tumor localization and parameter estimation using thermographic approach on GPU.

PubMed

Bousselham, Abdelmajid; Bouattane, Omar; Youssfi, Mohamed; Raihani, Abdelhadi

2018-01-01

The aim of this paper is to present a GPU parallel algorithm for brain tumor detection to estimate its size and location from surface temperature distribution obtained by thermography. The normal brain tissue is modeled as a rectangular cube including spherical tumor. The temperature distribution is calculated using forward three dimensional Pennes bioheat transfer equation, it's solved using massively parallel Finite Difference Method (FDM) and implemented on Graphics Processing Unit (GPU). Genetic Algorithm (GA) was used to solve the inverse problem and estimate the tumor size and location by minimizing an objective function involving measured temperature on the surface to those obtained by numerical simulation. The parallel implementation of Finite Difference Method reduces significantly the time of bioheat transfer and greatly accelerates the inverse identification of brain tumor thermophysical and geometrical properties. Experimental results show significant gains in the computational speed on GPU and achieve a speedup of around 41 compared to the CPU. The analysis performance of the estimation based on tumor size inside brain tissue also presented. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mercury and selenium levels, and selenium:mercury molar ratios of brain, muscle and other tissues in bluefish (Pomatomus saltatrix) from New Jersey, USA.

PubMed

Burger, Joanna; Jeitner, Christian; Donio, Mark; Pittfield, Taryn; Gochfeld, Michael

2013-01-15

A number of contaminants affect fish health, including mercury and selenium, and the selenium:mercury molar ratio. Recently the protective effects of selenium on methylmercury toxicity have been publicized, particularly for consumption of saltwater fish. Yet the relative ameliorating effects of selenium on toxicity within fish have not been examined, nor has the molar ratio in different tissues, (i.e. brain). We examined mercury and selenium levels in brain, kidney, liver, red and white muscle, and skin and scales in bluefish (Pomatomus saltatrix) (n=40) from New Jersey to determine whether there were toxic levels of either metal, and we computed the selenium:mercury molar ratios by tissues. Total mercury averaged 0.32±0.02 ppm wet weight in edible muscle and 0.09±0.01 ppm in brain. Selenium concentration averaged 0.37±0.03 in muscle and 0.36±0.03 ppm in brain. There were significant differences in levels of mercury, selenium, and selenium:mercury molar ratios, among tissues. Mercury and selenium levels were correlated in kidney and skin/scales. Mercury levels were highest in kidney, intermediate in muscle and liver, and lowest in brain and skin/scales; selenium levels were also highest in kidney, intermediate in liver, and were an order of magnitude lower in the white muscle and brain. Mercury levels in muscle, kidney and skin/scales were positively correlated with fish size (length). Selenium levels in muscle, kidney and liver were positively correlated with fish length, but in brain; selenium levels were negatively correlated with fish length. The selenium:mercury molar ratio was negatively correlated with fish length for white muscle, liver, kidney, and brain, particularly for fish over 50 cm in length, suggesting that older fish experience less protective advantages of selenium against mercury toxicity than smaller fish, and that consumers of bluefish similarly receive less advantage from eating larger fish. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of compression injury on brain mitochondrial and tissue viability evaluated by a multiparametric monitoring system

NASA Astrophysics Data System (ADS)

Barbiro-Michaely, Efrat; Bachbut, Galit; Mayevsky, Avraham

2008-02-01

Neurosurgical procedures involve brain compression created by retractors. Although it is clear that retractors are causing damage to the brain tissue, the pathophysiology of the retraction was not investigated in details. In the present study we used the multiparametric monitoring approach for real time evaluation of mitochondrial function, hemodynamic, ionic and electrical activities monitored contralaterally to the retractor placement on the brain. The aims of the study were to test the effects of retractor size and severity of the compression on the degree of damage to the cerebral tissue. A special probe was lowered towards the cerebral cortex, (2mm and 4mm in depth) using a micromanipulator. Compression lasted for 30 minutes, than the retractor was elevated back to its initial position and monitoring continued for two hours. Additionally, two sizes of retractors were used 6mm and 3mm in diameter, the 3mm retractor included an intracranial pressure (ICP) probe. The results show that the combination of a large retractor with the depth of 4mm yielded high mortality rate (62%) of the rats while the use of a smaller retractor decreased significantly the percentage of mortality. Also, compression to the depth of 4mm increased tissue injury as compared to 2mm depth. In conclusion, the present study raises the importance and significance of multiparametric monitoring, and not only ICP and cerebral blood flow of the areas nearby the retractor position and not only the retraction site, as well as the effect of the retractor size on the damage induced to the cerebral tissue.

Intraoperative monitoring of brain tissue oxygenation during arteriovenous malformation resection.

PubMed

Arikan, Fuat; Vilalta, Jordi; Noguer, Montserrat; Olive, Montserrat; Vidal-Jorge, Marian; Sahuquillo, Juan

2014-10-01

In normal perfusion pressure breakthrough (NPPB) it is assumed that following arteriovenous malformation (AVM) resection, vasoparalysis persists in the margins of the lesion and that a sudden increase in cerebral blood flow (CBF) after AVM exclusion leads to brain swelling and postsurgical complications. However, the pathophysiology NPPB remains controversial.The aim of our study was to investigate the oxygenation status in tissue surrounding AVMs and in the distant brain using intraoperative monitoring of cerebral partial pressure of oxygen (PtiO(2)) to achieve a better understanding of NPPB pathophysiology. Patients with supratentorial AVMs were monitored intraoperatively using 2 polarographic Clark-type electrodes. To establish reference values, we also studied PtiO(2) in a group of patients who underwent surgery to treat incidental aneurysms. Twenty-two patients with supratentorial AVMs and 16 patients with incidentally found aneurysms were included. Hypoxic pattern was defined as PtiO(2)≤15 mm Hg and/or PtiO(2)/PaO(2) ratio ≤0.10. Tissue hypoxia was detected in 63.6% of the catheters placed in the perinidal area and in 43.8% of catheters placed in a distant area. AVM excision significantly improved oxygenation both around the AVM and in the distant area. The PtiO(2)/PaO(2) ratio is a better indicator than absolute PtiO(2) in detecting tissue hypoxia in mechanically ventilated patients. Intraoperative monitoring showed tissue hypoxia in the margins of AVMs and in the distant ipsilateral brain as the most common finding. Surgical removal of AVMs induces a significant improvement in the oxygenation status in both areas.

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).

SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

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

Algan, O; Giem, J; Young, J

Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-testmore » analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.« less

Sensitive and specific detection of classical scrapie prions in the brains of goats by real-time quaking-induced conversion.

PubMed

Dassanayake, Rohana P; Orrú, Christina D; Hughson, Andrew G; Caughey, Byron; Graça, Telmo; Zhuang, Dongyue; Madsen-Bouterse, Sally A; Knowles, Donald P; Schneider, David A

2016-03-01

Real-time quaking-induced conversion (RT-QuIC) is a rapid, specific and highly sensitive prion seeding activity detection assay that uses recombinant prion protein (rPrPSen) to detect subinfectious levels of the abnormal isoforms of the prion protein (PrPSc). Although RT-QuIC has been successfully used to detect PrPSc in various tissues from humans and animals, including sheep, tissues from goats infected with classical scrapie have not yet been tested. Therefore, the aims of the present study were to (1) evaluate whether prion seeding activity could be detected in the brain tissues of goats with scrapie using RT-QuIC, (2) optimize reaction conditions to improve scrapie detection in goats, and (3) compare the performance of RT-QuIC for the detection of PrPSc with the more commonly used ELISA and Western blot assays. We further optimized RT-QuIC conditions for sensitive and specific detection of goat scrapie seeding activity in brain tissue from clinical animals. When used with 200  mM sodium chloride, both full-length sheep rPrPSen substrates (PrP genotypes A136R154Q171 and V136R154Q171) provided good discrimination between scrapie-infected and normal goat brain samples at 10(- )3 dilution within 15  h. Our findings indicate that RT-QuIC was at least 10,000-fold more sensitive than ELISA and Western blot assays for the detection of scrapie seeding activity in goat brain samples. In addition to PRNP WT samples, positive RT-QuIC reactions were also observed with three PRNP polymorphic goat brain samples (G/S127, I/M142 and H/R143) tested. Taken together, these findings demonstrate that RT-QuIC sensitively detects prion seeding activity in classical scrapie-infected goat brain samples.

Sensitive and specific detection of classical scrapie prions in the brains of goats by real-time quaking-induced conversion

PubMed Central

Dassanayake, Rohana P.; Orrú, Christina D.; Hughson, Andrew G.; Caughey, Byron; Graça, Telmo; Zhuang, Dongyue; Madsen-Bouterse, Sally A.; Knowles, Donald P.; Schneider, David A.

2016-01-01

Real-time quaking-induced conversion (RT-QuIC) is a rapid, specific and highly sensitive prion seeding activity detection assay that uses recombinant prion protein (rPrPSen) to detect subinfectious levels of the abnormal isoforms of the prion protein (PrPSc). Although RT-QuIC has been successfully used to detect PrPSc in various tissues from humans and animals, including sheep, tissues from goats infected with classical scrapie have not yet been tested. Therefore, the aims of the present study were to (1) evaluate whether prion seeding activity could be detected in the brain tissues of goats with scrapie using RT-QuIC, (2) optimize reaction conditions to improve scrapie detection in goats, and (3) compare the performance of RT-QuIC for the detection of PrPSc with the more commonly used ELISA and Western blot assays. We further optimized RT-QuIC conditions for sensitive and specific detection of goat scrapie seeding activity in brain tissue from clinical animals. When used with 200 mM sodium chloride, both full-length sheep rPrPSen substrates (PrP genotypes A136R154Q171 and V136R154Q171) provided good discrimination between scrapie-infected and normal goat brain samples at 10− 3 dilution within 15 h. Our findings indicate that RT-QuIC was at least 10 000-fold more sensitive than ELISA and Western blot assays for the detection of scrapie seeding activity in goat brain samples. In addition to PRNP WT samples, positive RT-QuIC reactions were also observed with three PRNP polymorphic goat brain samples (G/S127, I/M142 and H/R143) tested. Taken together, these findings demonstrate that RT-QuIC sensitively detects prion seeding activity in classical scrapie-infected goat brain samples. PMID:26653410

Metabolism as a tool for understanding human brain evolution: lipid energy metabolism as an example.

PubMed

Wang, Shu Pei; Yang, Hao; Wu, Jiang Wei; Gauthier, Nicolas; Fukao, Toshiyuki; Mitchell, Grant A

2014-12-01

Genes and the environment both influence the metabolic processes that determine fitness. To illustrate the importance of metabolism for human brain evolution and health, we use the example of lipid energy metabolism, i.e. the use of fat (lipid) to produce energy and the advantages that this metabolic pathway provides for the brain during environmental energy shortage. We briefly describe some features of metabolism in ancestral organisms, which provided a molecular toolkit for later development. In modern humans, lipid energy metabolism is a regulated multi-organ pathway that links triglycerides in fat tissue to the mitochondria of many tissues including the brain. Three important control points are each suppressed by insulin. (1) Lipid reserves in adipose tissue are released by lipolysis during fasting and stress, producing fatty acids (FAs) which circulate in the blood and are taken up by cells. (2) FA oxidation. Mitochondrial entry is controlled by carnitine palmitoyl transferase 1 (CPT1). Inside the mitochondria, FAs undergo beta oxidation and energy production in the Krebs cycle and respiratory chain. (3) In liver mitochondria, the 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) pathway produces ketone bodies for the brain and other organs. Unlike most tissues, the brain does not capture and metabolize circulating FAs for energy production. However, the brain can use ketone bodies for energy. We discuss two examples of genetic metabolic traits that may be advantageous under most conditions but deleterious in others. (1) A CPT1A variant prevalent in Inuit people may allow increased FA oxidation under nonfasting conditions but also predispose to hypoglycemic episodes. (2) The thrifty genotype theory, which holds that energy expenditure is efficient so as to maximize energy stores, predicts that these adaptations may enhance survival in periods of famine but predispose to obesity in modern dietary environments. Copyright © 2014 Elsevier Ltd. All rights reserved.

FDG-PET reproducibility in tumor-bearing mice: comparing a traditional SUV approach with a tumor-to-brain tissue ratio approach.

PubMed

Busk, Morten; Munk, Ole L; Jakobsen, Steen; Frøkiær, Jørgen; Overgaard, Jens; Horsman, Michael R

2017-05-01

Current [F-18]-fluorodeoxyglucose positron emission tomography (FDG-PET) procedures in tumor-bearing mice typically includes fasting, anesthesia, and standardized uptake value (SUV)-based quantification. Such procedures may be inappropriate for prolonged multiscan experiments. We hypothesize that normalization of tumor FDG retention relative to a suitable reference tissue may improve accuracy as this method may be less susceptible to uncontrollable day-to-day changes in blood glucose levels, physical activity, or unnoticed imperfect tail vein injections. Fed non-anesthetized tumor-bearing mice were administered FDG intravenously (i.v.) or intraperitoneally (i.p.) and PET scanned on consecutive days using a Mediso nanoScan PET/magnetic resonance imaging (MRI). Reproducibility of various PET-deduced measures of tumor FDG retention, including normalization to FDG signal in reference organs and a conventional SUV approach, was evaluated. Day-to-day variability in i.v. injected mice was lower when tumor FDG retention was normalized to brain signal (T/B), compared to normalization to other tissues or when using SUV-based normalization. Assessment of tissue radioactivity in dissected tissues confirmed the validity of PET-derived T/B ratios. Mean T/B and SUV values were similar in i.v. and i.p. administered animals, but SUV normalization was more robust in the i.p. group than in the i.v. group. Multimodality scanners allow tissue delineation and normalization of tumor FDG uptake relative to reference tissues. Normalization to brain, but not liver or kidney, improved scan reproducibility considerably and was superior to traditional SUV quantification in i.v. tracer-injected animals. Day-to-day variability in SUV's was lower in i.p. than in i.v. injected animals, and i.p. injections may therefore be a valuable alternative in prolonged rodent studies, where repeated vein injections are undesirable.

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.

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.

Prohormone convertase 7 is necessary for the normal processing of cholecystokinin in mouse brain.

PubMed

Anyetei-Anum, Emmanuel N; Blum, Alissa; Seidah, Nabil G; Beinfeld, Margery C

2017-01-22

Endoproteases in the secretory pathway process pro-cholecystokinin (CCK) into the biologically active forms found in the tissues that express CCK mRNA. Thus far, the endoproteases involved in CCK processing include cathepsin L and the prohormone convertases (PC) 1, 2, and 5. This study finds that PC7 is also critical for normal production of CCK in specific areas of the brain. Loss of PC7 results in decreased levels of CCK in more brain regions than any other endoprotease studied to date. Substantial decreases in brain levels of CCK are found in the prefrontal, frontal, parietal-insular-pyriform, and temporal cortex, caudate-putamen, basal forebrain, thalamus, hippocampus, septum, and medulla of PC7 knock-out (KO) mice. A tissue-specific sexual dimorphism of PC7 activity was also identified. This is the first report that loss of PC7 alters levels of a neuropeptide in the brain. This loss of PC7 and CCK may independently contribute to the decrease in Brain Derived Neurotrophic Factor production and be partially responsible for the learning and memory defects observed in mice that lack PC7. Copyright © 2016 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.

Tomographic brain imaging with nucleolar detail and automatic cell counting

NASA Astrophysics Data System (ADS)

Hieber, Simone E.; Bikis, Christos; Khimchenko, Anna; Schweighauser, Gabriel; Hench, Jürgen; Chicherova, Natalia; Schulz, Georg; Müller, Bert

2016-09-01

Brain tissue evaluation is essential for gaining in-depth insight into its diseases and disorders. Imaging the human brain in three dimensions has always been a challenge on the cell level. In vivo methods lack spatial resolution, and optical microscopy has a limited penetration depth. Herein, we show that hard X-ray phase tomography can visualise a volume of up to 43 mm3 of human post mortem or biopsy brain samples, by demonstrating the method on the cerebellum. We automatically identified 5,000 Purkinje cells with an error of less than 5% at their layer and determined the local surface density to 165 cells per mm2 on average. Moreover, we highlight that three-dimensional data allows for the segmentation of sub-cellular structures, including dendritic tree and Purkinje cell nucleoli, without dedicated staining. The method suggests that automatic cell feature quantification of human tissues is feasible in phase tomograms obtained with isotropic resolution in a label-free manner.

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

Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma.

PubMed

Tang, Jiaze; Huang, Ning; Zhang, Xiang; Zhou, Tao; Tan, Ying; Pi, Jiangli; Pi, Li; Cheng, Si; Zheng, Huzhi; Cheng, Yuan

2017-01-01

The extent of resection is a significant prognostic factor in glioma patients. However, the maximum safe resection level is difficult to determine due to the inherent infiltrative character of tumors. Recently, fluorescence-guided surgery has emerged as a new technique that allows safe resection of glioma. In this study, we constructed a new kind of quantum dot (QD)-labeled aptamer (QD-Apt) nanoprobe by conjugating aptamer 32 (A32) to the QDs surface, which can specially bind to the tumors. A32 is a single-stranded DNA capable of binding to the epidermal growth factor receptor variant III (EGFRvIII) specially distributed on the surface of glioma cells. To detect the expression of EGFRvIII in human brain tissues, 120 specimens, including 110 glioma tissues and 10 normal brain tissues, were examined by immunohistochemistry, and the results showed that the rate of positive expression of EGFRvIII in the glioma tissues was 41.82%, and 0.00% in normal brain tissues. Besides, the physiochemical properties of QD-Apt nanoparticles (NPs) were thoroughly characterized. Biocompatibility of the NPs was evaluated, and the results suggested that the QD-Apt was nontoxic in vivo and vitro. Furthermore, the use of the QD-Apt in labeling glioma cell lines and human brain glioma tissues, and target gliomas in situ was also investigated. We found that not only could QD-Apt specially bind to the U87-EGFRvIII glioma cells but also bind to human glioma tissues in vitro. Fluorescence imaging in vivo with orthotopic glioma model mice bearing U87-EGFRvIII showed that QD-Apt could penetrate the blood-brain barrier and then selectively accumulate in the tumors through binding to EGFRvIII, and consequently, generate a strong fluorescence, which contributed to the margins of gliomas that were visualized clearly, and thus, help the surgeons realize the maximum safe resection of glioma. In addition, QD-Apt can also be applied in preoperative diagnosis and postoperative examination of glioma. Therefore, these achievements facilitate the use of tumor-targeted fluorescence imaging in the diagnosis, surgical resection, and postoperative examination of glioma.

Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma

PubMed Central

Tang, Jiaze; Huang, Ning; Zhang, Xiang; Zhou, Tao; Tan, Ying; Pi, Jiangli; Pi, Li; Cheng, Si; Zheng, Huzhi; Cheng, Yuan

2017-01-01

The extent of resection is a significant prognostic factor in glioma patients. However, the maximum safe resection level is difficult to determine due to the inherent infiltrative character of tumors. Recently, fluorescence-guided surgery has emerged as a new technique that allows safe resection of glioma. In this study, we constructed a new kind of quantum dot (QD)-labeled aptamer (QD-Apt) nanoprobe by conjugating aptamer 32 (A32) to the QDs surface, which can specially bind to the tumors. A32 is a single-stranded DNA capable of binding to the epidermal growth factor receptor variant III (EGFRvIII) specially distributed on the surface of glioma cells. To detect the expression of EGFRvIII in human brain tissues, 120 specimens, including 110 glioma tissues and 10 normal brain tissues, were examined by immunohistochemistry, and the results showed that the rate of positive expression of EGFRvIII in the glioma tissues was 41.82%, and 0.00% in normal brain tissues. Besides, the physiochemical properties of QD-Apt nanoparticles (NPs) were thoroughly characterized. Biocompatibility of the NPs was evaluated, and the results suggested that the QD-Apt was nontoxic in vivo and vitro. Furthermore, the use of the QD-Apt in labeling glioma cell lines and human brain glioma tissues, and target gliomas in situ was also investigated. We found that not only could QD-Apt specially bind to the U87-EGFRvIII glioma cells but also bind to human glioma tissues in vitro. Fluorescence imaging in vivo with orthotopic glioma model mice bearing U87-EGFRvIII showed that QD-Apt could penetrate the blood–brain barrier and then selectively accumulate in the tumors through binding to EGFRvIII, and consequently, generate a strong fluorescence, which contributed to the margins of gliomas that were visualized clearly, and thus, help the surgeons realize the maximum safe resection of glioma. In addition, QD-Apt can also be applied in preoperative diagnosis and postoperative examination of glioma. Therefore, these achievements facilitate the use of tumor-targeted fluorescence imaging in the diagnosis, surgical resection, and postoperative examination of glioma. PMID:28579776

Hierarchical probabilistic Gabor and MRF segmentation of brain tumours in MRI volumes.

PubMed

Subbanna, Nagesh K; Precup, Doina; Collins, D Louis; Arbel, Tal

2013-01-01

In this paper, we present a fully automated hierarchical probabilistic framework for segmenting brain tumours from multispectral human brain magnetic resonance images (MRIs) using multiwindow Gabor filters and an adapted Markov Random Field (MRF) framework. In the first stage, a customised Gabor decomposition is developed, based on the combined-space characteristics of the two classes (tumour and non-tumour) in multispectral brain MRIs in order to optimally separate tumour (including edema) from healthy brain tissues. A Bayesian framework then provides a coarse probabilistic texture-based segmentation of tumours (including edema) whose boundaries are then refined at the voxel level through a modified MRF framework that carefully separates the edema from the main tumour. This customised MRF is not only built on the voxel intensities and class labels as in traditional MRFs, but also models the intensity differences between neighbouring voxels in the likelihood model, along with employing a prior based on local tissue class transition probabilities. The second inference stage is shown to resolve local inhomogeneities and impose a smoothing constraint, while also maintaining the appropriate boundaries as supported by the local intensity difference observations. The method was trained and tested on the publicly available MICCAI 2012 Brain Tumour Segmentation Challenge (BRATS) Database [1] on both synthetic and clinical volumes (low grade and high grade tumours). Our method performs well compared to state-of-the-art techniques, outperforming the results of the top methods in cases of clinical high grade and low grade tumour core segmentation by 40% and 45% respectively.

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

Development of a high-throughput brain slice method for studying drug distribution in the central nervous system.

PubMed

Fridén, Markus; Ducrozet, Frederic; Middleton, Brian; Antonsson, Madeleine; Bredberg, Ulf; Hammarlund-Udenaes, Margareta

2009-06-01

New, more efficient methods of estimating unbound drug concentrations in the central nervous system (CNS) combine the amount of drug in whole brain tissue samples measured by conventional methods with in vitro estimates of the unbound brain volume of distribution (V(u,brain)). Although the brain slice method is the most reliable in vitro method for measuring V(u,brain), it has not previously been adapted for the needs of drug discovery research. The aim of this study was to increase the throughput and optimize the experimental conditions of this method. Equilibrium of drug between the buffer and the brain slice within the 4 to 5 h of incubation is a fundamental requirement. However, it is difficult to meet this requirement for many of the extensively binding, lipophilic compounds in drug discovery programs. In this study, the dimensions of the incubation vessel and mode of stirring influenced the equilibration time, as did the amount of brain tissue per unit of buffer volume. The use of cassette experiments for investigating V(u,brain) in a linear drug concentration range increased the throughput of the method. The V(u,brain) for the model compounds ranged from 4 to 3000 ml . g brain(-1), and the sources of variability are discussed. The optimized setup of the brain slice method allows precise, robust estimation of V(u,brain) for drugs with diverse properties, including highly lipophilic compounds. This is a critical step forward for the implementation of relevant measurements of CNS exposure in the drug discovery setting.

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.

Determination of selected neurotoxic insecticides in small amounts of animal tissue utilizing a newly constructed mini-extractor.

PubMed

Seifertová, Marta; Čechová, Eliška; Llansola, Marta; Felipo, Vicente; Vykoukalová, Martina; Kočan, Anton

2017-10-01

We developed a simple analytical method for the simultaneous determination of representatives of various groups of neurotoxic insecticides (carbaryl, chlorpyrifos, cypermethrin, and α-endosulfan and β-endosulfan and their metabolite endosulfan sulfate) in limited amounts of animal tissues containing different amounts of lipids. Selected tissues (rodent fat, liver, and brain) were extracted in a special in-house-designed mini-extractor constructed on the basis of the Soxhlet and Twisselmann extractors. A dried tissue sample placed in a small cartridge was extracted, while the nascent extract was simultaneously filtered through a layer of sodium sulfate. The extraction was followed by combined clean-up, including gel permeation chromatography (in case of high lipid content), ultrasonication, and solid-phase extraction chromatography using C 18 on silica and aluminum oxide. Gas chromatography coupled with high-resolution mass spectrometry was used for analyte separation, detection, and quantification. Average recoveries for individual insecticides ranged from 82 to 111%. Expanded measurement uncertainties were generally lower than 35%. The developed method was successfully applied to rat tissue samples obtained from an animal model dealing with insecticide exposure during brain development. This method may also be applied to the analytical treatment of small amounts of various types of animal and human tissue samples. A significant advantage achieved using this method is high sample throughput due to the simultaneous treatment of many samples. Graphical abstract Optimized workflow for the determination of selected insecticides in small amounts of animal tissue including newly developed mini-extractor.

Proposal Guidelines for Standardized Operating Procedures of Brain Autopsy: Brain Bank in South Korea.

PubMed

Lee, Kyung Hwa; Seo, Sang Won; Lim, Tae Sung; Kim, Eun Joo; Kim, Byeong Chae; Kim, Yeshin; Lee, Ho Won; Jeon, Jae Pil; Shim, Sung Mi; Na, Duk L; Huh, Gi Yeong; Lee, Min Cheol; Suh, Yeon Lim

2017-09-01

To obtain an in-depth understanding of brain diseases, including neurodegenerative diseases, psychiatric illnesses, and neoplasms, scientific approach and verification using postmortem human brain tissue with or without disease are essential. Compared to other countries that have run brain banks for decades, South Korea has limited experience with brain banking; nationwide brain banks started only recently. The goal of this study is to provide provisional guidelines for brain autopsy for hospitals and institutes that have not accumulated sufficient expertise. We hope that these provisional guidelines will serve as a useful reference for pathologists and clinicians who are involved and interested in the brain bank system. Also, we anticipate updating the provisional guidelines in the future based on collected data and further experience with the practice of brain autopsy in South Korea. © Copyright: Yonsei University College of Medicine 2017.

Intronic SNP in ESR1 encoding human estrogen receptor alpha is associated with brain ESR1 mRNA isoform expression and behavioral traits.

PubMed

Pinsonneault, Julia K; Frater, John T; Kompa, Benjamin; Mascarenhas, Roshan; Wang, Danxin; Sadee, Wolfgang

2017-01-01

Genetic variants of ESR1 have been implicated in multiple diseases, including behavioral disorders, but causative variants remain uncertain. We have searched for regulatory variants affecting ESR1 expression in human brain, measuring allelic ESR1 mRNA expression in human brain tissues with marker SNPs in exon4 representing ESR1-008 (or ESRα-36), and in the 3'UTR of ESR1-203, two main ESR1 isoforms in brain. In prefrontal cortex from subjects with bipolar disorder, schizophrenia, and controls (n = 35 each; Stanley Foundation brain bank), allelic ESR1 mRNA ratios deviated from unity up to tenfold at the exon4 marker SNP, with large allelic ratios observed primarily in bipolar and schizophrenic subjects. SNP scanning and targeted sequencing identified rs2144025, associated with large allelic mRNA ratios (p = 1.6E10-6). Moreover, rs2144025 was significantly associated with ESR1 mRNA levels in the Brain eQTL Almanac and in brain regions in the Genotype-Tissue Expression project. In four GWAS cohorts, rs2104425 was significantly associated with behavioral traits, including: hypomanic episodes in female bipolar disorder subjects (GAIN bipolar disorder study; p = 0.0004), comorbid psychological symptoms in both males and females with attention deficit hyperactivity disorder (GAIN ADHD, p = 0.00002), psychological diagnoses in female children (eMERGE study of childhood health, subject age ≥9, p = 0.0009), and traits in schizophrenia (e.g., grandiose delusions, GAIN schizophrenia, p = 0.0004). The first common ESR1 variant (MAF 12-33% across races) linked to regulatory functions, rs2144025 appears conditionally to affect ESR1 mRNA expression in the brain and modulate traits in behavioral disorders.

Intronic SNP in ESR1 encoding human estrogen receptor alpha is associated with brain ESR1 mRNA isoform expression and behavioral traits

PubMed Central

Kompa, Benjamin; Mascarenhas, Roshan; Wang, Danxin; Sadee, Wolfgang

2017-01-01

Genetic variants of ESR1 have been implicated in multiple diseases, including behavioral disorders, but causative variants remain uncertain. We have searched for regulatory variants affecting ESR1 expression in human brain, measuring allelic ESR1 mRNA expression in human brain tissues with marker SNPs in exon4 representing ESR1-008 (or ESRα-36), and in the 3’UTR of ESR1-203, two main ESR1 isoforms in brain. In prefrontal cortex from subjects with bipolar disorder, schizophrenia, and controls (n = 35 each; Stanley Foundation brain bank), allelic ESR1 mRNA ratios deviated from unity up to tenfold at the exon4 marker SNP, with large allelic ratios observed primarily in bipolar and schizophrenic subjects. SNP scanning and targeted sequencing identified rs2144025, associated with large allelic mRNA ratios (p = 1.6E10-6). Moreover, rs2144025 was significantly associated with ESR1 mRNA levels in the Brain eQTL Almanac and in brain regions in the Genotype-Tissue Expression project. In four GWAS cohorts, rs2104425 was significantly associated with behavioral traits, including: hypomanic episodes in female bipolar disorder subjects (GAIN bipolar disorder study; p = 0.0004), comorbid psychological symptoms in both males and females with attention deficit hyperactivity disorder (GAIN ADHD, p = 0.00002), psychological diagnoses in female children (eMERGE study of childhood health, subject age ≥9, p = 0.0009), and traits in schizophrenia (e.g., grandiose delusions, GAIN schizophrenia, p = 0.0004). The first common ESR1 variant (MAF 12–33% across races) linked to regulatory functions, rs2144025 appears conditionally to affect ESR1 mRNA expression in the brain and modulate traits in behavioral disorders. PMID:28617822

Circadian rhythmicity and light sensitivity of the zebrafish brain.

PubMed

Moore, Helen A; Whitmore, David

2014-01-01

Traditionally, circadian clocks have been thought of as a neurobiological phenomenon. This view changed somewhat over recent years with the discovery of peripheral tissue circadian oscillators. In mammals, however, the suprachiasmatic nucleus (SCN) in the hypothalamus still retains the critical role of a central synchronizer of biological timing. Zebrafish, in contrast, have always reflected a more highly decentralized level of clock organization, as individual cells and tissues contain directly light responsive circadian pacemakers. As a consequence, clock function in the zebrafish brain has remained largely unexplored, and the precise organization of rhythmic and light-sensitive neurons within the brain is unknown. To address this issue, we used the period3 (per3)-luciferase transgenic zebrafish to confirm that multiple brain regions contain endogenous circadian oscillators that are directly light responsive. In addition, in situ hybridization revealed localised neural expression of several rhythmic and light responsive clock genes, including per3, cryptochrome1a (cry1a) and per2. Adult brain nuclei showing significant clock gene expression include the teleost equivalent of the SCN, as well as numerous hypothalamic nuclei, the periventricular grey zone (PGZ) of the optic tectum, and granular cells of the rhombencephalon. To further investigate the light sensitive properties of neurons, expression of c-fos, a marker for neuronal activity, was examined. c-fos mRNA was upregulated in response to changing light conditions in different nuclei within the zebrafish brain. Furthermore, under constant dark (DD) conditions, c-fos shows a significant circadian oscillation. Taken together, these results show that there are numerous areas of the zebrafish central nervous system, which contain deep brain photoreceptors and directly light-entrainable circadian pacemakers. However, there are also multiple brain nuclei, which possess neither, demonstrating a degree of pacemaker complexity that was not previously appreciated.

Circadian Rhythmicity and Light Sensitivity of the Zebrafish Brain

PubMed Central

Moore, Helen A.; Whitmore, David

2014-01-01

Traditionally, circadian clocks have been thought of as a neurobiological phenomenon. This view changed somewhat over recent years with the discovery of peripheral tissue circadian oscillators. In mammals, however, the suprachiasmatic nucleus (SCN) in the hypothalamus still retains the critical role of a central synchronizer of biological timing. Zebrafish, in contrast, have always reflected a more highly decentralized level of clock organization, as individual cells and tissues contain directly light responsive circadian pacemakers. As a consequence, clock function in the zebrafish brain has remained largely unexplored, and the precise organization of rhythmic and light-sensitive neurons within the brain is unknown. To address this issue, we used the period3 (per3)-luciferase transgenic zebrafish to confirm that multiple brain regions contain endogenous circadian oscillators that are directly light responsive. In addition, in situ hybridization revealed localised neural expression of several rhythmic and light responsive clock genes, including per3, cryptochrome1a (cry1a) and per2. Adult brain nuclei showing significant clock gene expression include the teleost equivalent of the SCN, as well as numerous hypothalamic nuclei, the periventricular grey zone (PGZ) of the optic tectum, and granular cells of the rhombencephalon. To further investigate the light sensitive properties of neurons, expression of c-fos, a marker for neuronal activity, was examined. c-fos mRNA was upregulated in response to changing light conditions in different nuclei within the zebrafish brain. Furthermore, under constant dark (DD) conditions, c-fos shows a significant circadian oscillation. Taken together, these results show that there are numerous areas of the zebrafish central nervous system, which contain deep brain photoreceptors and directly light-entrainable circadian pacemakers. However, there are also multiple brain nuclei, which possess neither, demonstrating a degree of pacemaker complexity that was not previously appreciated. PMID:24465943

Comprehensive Analysis of Human Endogenous Retrovirus Group HERV-W Locus Transcription in Multiple Sclerosis Brain Lesions by High-Throughput Amplicon Sequencing

PubMed Central

Schmitt, Katja; Richter, Christin; Backes, Christina; Meese, Eckart; Ruprecht, Klemens

2013-01-01

Human endogenous retroviruses (HERVs) of the HERV-W group comprise hundreds of loci in the human genome. Deregulated HERV-W expression and HERV-W locus ERVWE1-encoded Syncytin-1 protein have been implicated in the pathogenesis of multiple sclerosis (MS). However, the actual transcription of HERV-W loci in the MS context has not been comprehensively analyzed. We investigated transcription of HERV-W in MS brain lesions and white matter brain tissue from healthy controls by employing next-generation amplicon sequencing of HERV-W env-specific reverse transcriptase (RT) PCR products, thus revealing transcribed HERV-W loci and the relative transcript levels of those loci. We identified more than 100 HERV-W loci that were transcribed in the human brain, with a limited number of loci being predominantly transcribed. Importantly, relative transcript levels of HERV-W loci were very similar between MS and healthy brain tissue samples, refuting deregulated transcription of HERV-W env in MS brain lesions, including the high-level-transcribed ERVWE1 locus encoding Syncytin-1. Quantitative RT-PCR likewise did not reveal differences in MS regarding HERV-W env general transcript or ERVWE1- and ERVWE2-specific transcript levels. However, we obtained evidence for interindividual differences in HERV-W transcript levels. Reporter gene assays indicated promoter activity of many HERV-W long terminal repeats (LTRs), including structurally incomplete LTRs. Our comprehensive analysis of HERV-W transcription in the human brain thus provides important information on the biology of HERV-W in MS lesions and normal human brain, implications for study design, and mechanisms by which HERV-W may (or may not) be involved in MS. PMID:24109235

Ribosome Profiling Reveals a Cell-Type-Specific Translational Landscape in Brain Tumors

PubMed Central

Gonzalez, Christian; Sims, Jennifer S.; Hornstein, Nicholas; Mela, Angeliki; Garcia, Franklin; Lei, Liang; Gass, David A.; Amendolara, Benjamin; Bruce, Jeffrey N.

2014-01-01

Glioma growth is driven by signaling that ultimately regulates protein synthesis. Gliomas are also complex at the cellular level and involve multiple cell types, including transformed and reactive cells in the brain tumor microenvironment. The distinct functions of the various cell types likely lead to different requirements and regulatory paradigms for protein synthesis. Proneural gliomas can arise from transformation of glial progenitors that are driven to proliferate via mitogenic signaling that affects translation. To investigate translational regulation in this system, we developed a RiboTag glioma mouse model that enables cell-type-specific, genome-wide ribosome profiling of tumor tissue. Infecting glial progenitors with Cre-recombinant retrovirus simultaneously activates expression of tagged ribosomes and delivers a tumor-initiating mutation. Remarkably, we find that although genes specific to transformed cells are highly translated, their translation efficiencies are low compared with normal brain. Ribosome positioning reveals sequence-dependent regulation of ribosomal activity in 5′-leaders upstream of annotated start codons, leading to differential translation in glioma compared with normal brain. Additionally, although transformed cells express a proneural signature, untransformed tumor-associated cells, including reactive astrocytes and microglia, express a mesenchymal signature. Finally, we observe the same phenomena in human disease by combining ribosome profiling of human proneural tumor and non-neoplastic brain tissue with computational deconvolution to assess cell-type-specific translational regulation. PMID:25122893

In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

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

Weaver, John, E-mail: jmweaver@salud.unm.edu; Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131; Yang, Yirong

2014-03-01

Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O{sub 2} may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O{sub 2} is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO{sub 2}in vivo remains largely uncharacterized. This study investigated striatal tissuemore » pO{sub 2} changes in male C57BL/6 mice (16–20 g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO{sub 2}in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO{sub 2} was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO{sub 2} to 64%. More importantly, pO{sub 2} did not recover fully to control levels even 24 h after administration of a single dose of METH and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO{sub 2} indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO{sub 2}, which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults. - Highlights: • Explored striatal tissue pO{sub 2}in vivo after METH administration by EPR oximetry. • pO{sub 2} was reduced by 81% after a single dose and 64% after 3 consecutive daily doses. • pO{sub 2} did not recover fully to control levels even 24 h after a single dose. • Decrease in brain tissue pO{sub 2} may be associated with a decrease in CBF. • Administration of methamphetamine may lead to hypoxic insult.« less

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.

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.

HdhQ111 Mice Exhibit Tissue Specific Metabolite Profiles that Include Striatal Lipid Accumulation

PubMed Central

Carroll, Jeffrey B.; Deik, Amy; Fossale, Elisa; Weston, Rory M.; Guide, Jolene R.; Arjomand, Jamshid; Kwak, Seung; Clish, Clary B.; MacDonald, Marcy E.

2015-01-01

The HTT CAG expansion mutation causes Huntington’s Disease and is associated with a wide range of cellular consequences, including altered metabolism. The mutant allele is expressed widely, in all tissues, but the striatum and cortex are especially vulnerable to its effects. To more fully understand this tissue-specificity, early in the disease process, we asked whether the metabolic impact of the mutant CAG expanded allele in heterozygous B6.HdhQ111/+ mice would be common across tissues, or whether tissues would have tissue-specific responses and whether such changes may be affected by diet. Specifically, we cross-sectionally examined steady state metabolite concentrations from a range of tissues (plasma, brown adipose tissue, cerebellum, striatum, liver, white adipose tissue), using an established liquid chromatography-mass spectrometry pipeline, from cohorts of 8 month old mutant and wild-type littermate mice that were fed one of two different high-fat diets. The differential response to diet highlighted a proportion of metabolites in all tissues, ranging from 3% (7/219) in the striatum to 12% (25/212) in white adipose tissue. By contrast, the mutant CAG-expanded allele primarily affected brain metabolites, with 14% (30/219) of metabolites significantly altered, compared to wild-type, in striatum and 11% (25/224) in the cerebellum. In general, diet and the CAG-expanded allele both elicited metabolite changes that were predominantly tissue-specific and non-overlapping, with evidence for mutation-by-diet interaction in peripheral tissues most affected by diet. Machine-learning approaches highlighted the accumulation of diverse lipid species as the most genotype-predictive metabolite changes in the striatum. Validation experiments in cell culture demonstrated that lipid accumulation was also a defining feature of mutant HdhQ111 striatal progenitor cells. Thus, metabolite-level responses to the CAG expansion mutation in vivo were tissue specific and most evident in brain, where the striatum featured signature accumulation of a set of lipids including sphingomyelin, phosphatidylcholine, cholesterol ester and triglyceride species. Importantly, in the presence of the CAG mutation, metabolite changes were unmasked in peripheral tissues by an interaction with dietary fat, implying that the design of studies to discover metabolic changes in HD mutation carriers should include metabolic perturbations. PMID:26295712

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.

γδ T cells as early sensors of tissue damage and mediators of secondary neurodegeneration

PubMed Central

Gelderblom, Mathias; Arunachalam, Priyadharshini; Magnus, Tim

2014-01-01

Spontaneous or medically induced reperfusion occurs in up to 70% of patients within 24 h after cerebral ischemia. Reperfusion of ischemic brain tissue can augment the inflammatory response that causes additional injury. Recently, T cells have been shown to be an essential part of the post-ischemic tissue damage, and especially IL-17 secreting T cells have been implicated in the pathogenesis of a variety of inflammatory reactions in the brain. After stroke, it seems that the innate γδ T cells are the main IL-17 producing cells and that the γδ T cell activation constitutes an early and mainly damaging immune response in stroke. Effector mechanism of γδ T cell derived IL-17 in the ischemic brain include the induction of metalloproteinases, proinflammatory cytokines and neutrophil attracting chemokines, leading to a further amplification of the detrimental inflammatory response. In this review, we will give an overview on the concepts of γδ T cells and IL-17 in stroke pathophysiology and on their potential importance for human disease conditions. PMID:25414640

Ischemic brain injury in cerebral amyloid angiopathy

PubMed Central

van Veluw, Susanne J; Greenberg, Steven M

2016-01-01

Cerebral amyloid angiopathy (CAA) is a common form of cerebral small vessel disease and an important risk factor for intracerebral hemorrhage and cognitive impairment. While the majority of research has focused on the hemorrhagic manifestation of CAA, its ischemic manifestations appear to have substantial clinical relevance as well. Findings from imaging and pathologic studies indicate that ischemic lesions are common in CAA, including white-matter hyperintensities, microinfarcts, and microstructural tissue abnormalities as detected with diffusion tensor imaging. Furthermore, imaging markers of ischemic disease show a robust association with cognition, independent of age, hemorrhagic lesions, and traditional vascular risk factors. Widespread ischemic tissue injury may affect cognition by disrupting white-matter connectivity, thereby hampering communication between brain regions. Challenges are to identify imaging markers that are able to capture widespread microvascular lesion burden in vivo and to further unravel the etiology of ischemic tissue injury by linking structural magnetic resonance imaging (MRI) abnormalities to their underlying pathophysiology and histopathology. A better understanding of the underlying mechanisms of ischemic brain injury in CAA will be a key step toward new interventions to improve long-term cognitive outcomes for patients with CAA. PMID:25944592

Detecting occlusion inside a ventricular catheter using photoacoustic imaging through skull

NASA Astrophysics Data System (ADS)

Tavakoli, Behnoosh; Guo, Xiaoyu; Taylor, Russell H.; Kang, Jin U.; Boctor, Emad M.

2014-03-01

Ventricular catheters are used to treat hydrocephalus by diverting the excess of the cerebrospinal fluid (CSF) to the reabsorption site so as to regulate the intracranial pressure. The failure rate of these shunts is extremely high due to the ingrown tissue that blocks the CSF flow. We have studied a method to image the occlusion inside the shunt through the skull. In this approach the pulsed laser light coupled to the optical fiber illuminate the occluding tissue inside the catheter and an external ultrasound transducer is applied to detect the generated photoacoustic signal. The feasibility of this method is investigated using a phantom made of ovis aries brain tissue and adult human skull. We were able to image the target inside the shunt located 20mm deep inside the brain through about 4mm thick skull bone. This study could lead to the development of a simple, safe and non-invasive device for percutaneous restoration of patency to occluded shunts. This will eliminate the need of the surgical replacement of the occluded catheters which expose the patients to risks including hemorrhage and brain injury.

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.

Assessment of FUS-Tissue Interactions In Vivo

NASA Astrophysics Data System (ADS)

Haritonova, Alyona V.

Focused ultrasound (FUS) has been proposed for a variety of minimally invasive therapeutic applications, including tumor ablation, neuromodulation, targeted drug delivery and blood brain barrier opening. To date, FUS beams have been primarily monitored through MR and ultrasound diagnostic imaging modalities. The recent introduction of real-time dual-mode ultrasound array (DMUA) systems offers a new paradigm for the guidance of therapeutic focused ultrasound. The DMUA approach allows for inherent registration between the therapeutic and imaging coordinate systems. In this thesis we investigated the use of ultrasound-based thermography to assess FUS-tissue interactions. Specifically, we focused on two aspects of image-guided therapy: 1) monitoring and localization of FUS-tissue interactions, and 2) tissue damage assessment. Towards this end, we presented first experimental results of ultrasound-guided transcranial FUS in a rat brain, both ex vivo and in vivo. DMUA imaging was used to monitor and localize FUS-tissue thermal interactions in real-time. The transcranial echo data allowed for a reliable estimation of temperature change in brain tissue, which had never been done before using ultrasound image guidance. Despite some measurable distortion and loss in focusing gain, transcranial FUS beams at 3.2 MHz were localized axially and laterally. This confirms the results obtained using DMUA-based transcranial ultrasound thermography. A high degree of focusing with the DMUA was then successfully leveraged to perform localized tissue damage assessment in both ex vivo and in vivo. The experimental results presented in this thesis demonstrate some of the unique aspects of image guidance using DMUAs, especially when FUS is subject to significant distortions as in transcranial applications.

VA's National PTSD Brain Bank: a National Resource for Research.

PubMed

Friedman, Matthew J; Huber, Bertrand R; Brady, Christopher B; Ursano, Robert J; Benedek, David M; Kowall, Neil W; McKee, Ann C

2017-08-25

The National PTSD Brain Bank (NPBB) is a brain tissue biorepository established to support research on the causes, progression, and treatment of PTSD. It is a six-part consortium led by VA's National Center for PTSD with participating sites at VA medical centers in Boston, MA; Durham, NC; Miami, FL; West Haven, CT; and White River Junction, VT along with the Uniformed Services University of Health Sciences. It is also well integrated with VA's Boston-based brain banks that focus on Alzheimer's disease, ALS, chronic traumatic encephalopathy, and other neurological disorders. This article describes the organization and operations of NPBB with specific attention to: tissue acquisition, tissue processing, diagnostic assessment, maintenance of a confidential data biorepository, adherence to ethical standards, governance, accomplishments to date, and future challenges. Established in 2014, NPBB has already acquired and distributed brain tissue to support research on how PTSD affects brain structure and function.

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.

Brain and visceral involvement during congenital cytomegalovirus infection of guinea pigs.

PubMed

Griffith, B P; Lucia, H L; Hsiung, G D

1982-06-01

The virologic and histologic characteristics of congenital cytomegalovirus infection (CMV) were defined in 65 neonatal guinea pigs born from 27 mothers infected pregnancy. Infectious virus or tissue lesions were present in 54% of the neonates tested. Guinea pig CMV was detected most often in the salivary glands (72%) and spleen (33%) of infected guinea pigs. Less frequently, virus was also detected in the brain, lung, pancreas and liver. Tissue lesions were most frequently observed in the brain and kidney, but also occurred in the salivary glands, liver, pancreas, thymus and spleen. The histopathology was identical to that observed in infants with congenital CMV infection. Infectious virus and histopathology were present in newborn guinea pigs born from mothers infected at any time during gestation. Newborns from mothers infected during early stages of gestation and virus present most frequently in the salivary glands, whereas offspring of mothers infected in late pregnancy had virus present in several tissues. Acute maternal guinea pig CMV infection produced generalized CMV infection of the offspring which was followed by persistent infection in neonatal salivary glands. Lesions remained present in several neonatal tissues including the brain. The long term consequences of such lesions in affected guinea pigs remain to be determined. The results of the study emphasize the similarities between human congenital CMV infection and congenital guinea pig CMV infection, thereby underlining the utility of this animal model as a means of understanding human congenital CMV infection.

Neurotoxic responses in brain tissues of rainbow trout exposed to imidacloprid pesticide: Assessment of 8-hydroxy-2-deoxyguanosine activity, oxidative stress and acetylcholinesterase activity.

PubMed

Topal, Ahmet; Alak, Gonca; Ozkaraca, Mustafa; Yeltekin, Aslı Cilingir; Comaklı, Selim; Acıl, Gurdal; Kokturk, Mine; Atamanalp, Muhammed

2017-05-01

The extensive use of imidacloprid, a neonicotinoid insecticide, causes undesirable toxicity in non-targeted organisms including fish in aquatic environments. We investigated neurotoxic responses by observing 8-hydroxy-2-deoxyguanosine (8-OHdG) activity, oxidative stress and acetylcholinesterase (AChE) activity in rainbow trout brain tissue after 21 days of imidacloprid exposure at levels of (5 mg/L, 10 mg/L, 20 mg/L). The obtained results indicated that 8-OHdG activity did not change in fish exposed to 5 mg/L of imidacloprid, but 10 mg/L and 20 mg/L of imidacloprid significantly increased 8-OHdG activity compared to the control (p < 0.05). An immunopositiv reaction to 8-OHdG was detected in brain tissues. The brain tissues indicated a significant increase in antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)) compared to the control and there was a significant increase in malondialdehyde (MDA) levels (p < 0.05). High concentrations of imidacloprid caused a significant decrease in AChE enzyme activity (p < 0.05). These results suggested that imidacloprid can be neurotoxic to fish by promoting AChE inhibition, an increase in 8-OHdG activity and changes in oxidative stress parameters. Therefore, these data may reflect one of the molecular pathways that play a role in imidacloprid toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

PET Quantification of the Norepinephrine Transporter in Human Brain with (S,S)-18F-FMeNER-D2.

PubMed

Moriguchi, Sho; Kimura, Yasuyuki; Ichise, Masanori; Arakawa, Ryosuke; Takano, Harumasa; Seki, Chie; Ikoma, Yoko; Takahata, Keisuke; Nagashima, Tomohisa; Yamada, Makiko; Mimura, Masaru; Suhara, Tetsuya

2017-07-01

Norepinephrine transporter (NET) in the brain plays important roles in human cognition and the pathophysiology of psychiatric disorders. Two radioligands, ( S , S )- 11 C-MRB and ( S , S )- 18 F-FMeNER-D 2 , have been used for imaging NETs in the thalamus and midbrain (including locus coeruleus) using PET in humans. However, NET density in the equally important cerebral cortex has not been well quantified because of unfavorable kinetics with ( S , S )- 11 C-MRB and defluorination with ( S , S )- 18 F-FMeNER-D 2 , which can complicate NET quantification in the cerebral cortex adjacent to the skull containing defluorinated 18 F radioactivity. In this study, we have established analysis methods of quantification of NET density in the brain including the cerebral cortex using ( S , S )- 18 F-FMeNER-D 2 PET. Methods: We analyzed our previous ( S , S )- 18 F-FMeNER-D 2 PET data of 10 healthy volunteers dynamically acquired for 240 min with arterial blood sampling. The effects of defluorination on the NET quantification in the superficial cerebral cortex was evaluated by establishing a time stability of NET density estimations with an arterial input 2-tissue-compartment model, which guided the less-invasive reference tissue model and area under the time-activity curve methods to accurately quantify NET density in all brain regions including the cerebral cortex. Results: Defluorination of ( S , S )- 18 F-FMeNER-D 2 became prominent toward the latter half of the 240-min scan. Total distribution volumes in the superficial cerebral cortex increased with the scan duration beyond 120 min. We verified that 90-min dynamic scans provided a sufficient amount of data for quantification of NET density unaffected by defluorination. Reference tissue model binding potential values from the 90-min scan data and area under the time-activity curve ratios of 70- to 90-min data allowed for the accurate quantification of NET density in the cerebral cortex. Conclusion: We have established methods of quantification of NET densities in the brain including the cerebral cortex unaffected by defluorination using ( S , S )- 18 F-FMeNER-D 2 These results suggest that we can accurately quantify NET density with a 90-min ( S , S )- 18 F-FMeNER-D 2 scan in broad brain areas. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Quantification of Neural Ethanol and Acetaldehyde Using Headspace GC-MS

PubMed Central

Heit, Claire; Eriksson, Peter; Thompson, David C; Fritz, Kristofer S; Vasiliou, Vasilis

2016-01-01

BACKGROUND There is controversy regarding the active agent responsible for alcohol addiction. The theory that ethanol itself was the agent in alcohol drinking behavior was widely accepted until acetaldehyde was found in the brain. The importance of acetaldehyde formation in the brain role is still subject to speculation due to the lack of a method to accurately assay the acetaldehyde levels directly. A highly sensitive GC-MS method to reliably determine acetaldehyde concentration with certainty is needed to address whether neural acetaldehyde is indeed responsible for increased alcohol consumption. METHODS A headspace gas chromatograph coupled to selected ion monitoring mass spectrometry was utilized to develop a quantitative assay for acetaldehyde and ethanol. Our GC-MS approach was carried out using a Bruker Scion 436-GC SQ MS. RESULTS Our approach yields limits of detection of acetaldehyde in the nanomolar range and limits of quantification in the low micromolar range. Our linear calibration includes 5 concentrations with a least square regression greater than 0.99 for both acetaldehyde and ethanol. Tissue analyses using this method revealed the capacity to quantify ethanol and acetaldehyde in blood, brain, and liver tissue from mice. CONCLUSIONS By allowing quantification of very low concentrations, this method may be used to examine the formation of ethanol metabolites, specifically acetaldehyde, in murine brain tissue in alcohol research. PMID:27501276

Microwave & Magnetic (M2) Proteomics Reveals CNS-Specific Protein Expression Waves that Precede Clinical Symptoms of Experimental Autoimmune Encephalomyelitis

NASA Astrophysics Data System (ADS)

Raphael, Itay; Mahesula, Swetha; Purkar, Anjali; Black, David; Catala, Alexis; Gelfond, Jonathon A. L.; Forsthuber, Thomas G.; Haskins, William E.

2014-09-01

Central nervous system-specific proteins (CSPs), transported across the damaged blood-brain-barrier (BBB) to cerebrospinal fluid (CSF) and blood (serum), might be promising diagnostic, prognostic and predictive protein biomarkers of disease in individual multiple sclerosis (MS) patients because they are not expected to be present at appreciable levels in the circulation of healthy subjects. We hypothesized that microwave & magnetic (M2) proteomics of CSPs in brain tissue might be an effective means to prioritize putative CSP biomarkers for future immunoassays in serum. To test this hypothesis, we used M2 proteomics to longitudinally assess CSP expression in brain tissue from mice during experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Confirmation of central nervous system (CNS)-infiltrating inflammatory cell response and CSP expression in serum was achieved with cytokine ELISPOT and ELISA immunoassays, respectively, for selected CSPs. M2 proteomics (and ELISA) revealed characteristic CSP expression waves, including synapsin-1 and α-II-spectrin, which peaked at day 7 in brain tissue (and serum) and preceded clinical EAE symptoms that began at day 10 and peaked at day 20. Moreover, M2 proteomics supports the concept that relatively few CNS-infiltrating inflammatory cells can have a disproportionally large impact on CSP expression prior to clinical manifestation of EAE.

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.

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.

MO-F-CAMPUS-J-04: Tissue Segmentation-Based MR Electron Density Mapping Method for MR-Only Radiation Treatment Planning of Brain

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

Yu, H; Lee, Y; Ruschin, M

2015-06-15

Purpose: Automatically derive electron density of tissues using MR images and generate a pseudo-CT for MR-only treatment planning of brain tumours. Methods: 20 stereotactic radiosurgery (SRS) patients’ T1-weighted MR images and CT images were retrospectively acquired. First, a semi-automated tissue segmentation algorithm was developed to differentiate tissues with similar MR intensities and large differences in electron densities. The method started with approximately 12 slices of manually contoured spatial regions containing sinuses and airways, then air, bone, brain, cerebrospinal fluid (CSF) and eyes were automatically segmented using edge detection and anatomical information including location, shape, tissue uniformity and relative intensity distribution.more » Next, soft tissues - muscle and fat were segmented based on their relative intensity histogram. Finally, intensities of voxels in each segmented tissue were mapped into their electron density range to generate pseudo-CT by linearly fitting their relative intensity histograms. Co-registered CT was used as a ground truth. The bone segmentations of pseudo-CT were compared with those of co-registered CT obtained by using a 300HU threshold. The average distances between voxels on external edges of the skull of pseudo-CT and CT in three axial, coronal and sagittal slices with the largest width of skull were calculated. The mean absolute electron density (in Hounsfield unit) difference of voxels in each segmented tissues was calculated. Results: The average of distances between voxels on external skull from pseudo-CT and CT were 0.6±1.1mm (mean±1SD). The mean absolute electron density differences for bone, brain, CSF, muscle and fat are 78±114 HU, and 21±8 HU, 14±29 HU, 57±37 HU, and 31±63 HU, respectively. Conclusion: The semi-automated MR electron density mapping technique was developed using T1-weighted MR images. The generated pseudo-CT is comparable to that of CT in terms of anatomical position of tissues and similarity of electron density assignment. This method can allow MR-only treatment planning.« less

Distinct structure and activity of monoamine oxidase in the brain of zebrafish (Danio rerio).

PubMed

Anichtchik, Oleg; Sallinen, Ville; Peitsaro, Nina; Panula, Pertti

2006-10-10

Monoamine oxidase (MAO) is a mitochondrial flavoprotein involved in the metabolism of, e.g., aminergic neurotransmitters and the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). We have reported earlier MPTP-related alterations of brain catecholaminergic system in zebrafish (Danio rerio) brain. Here we describe the structural and functional properties of zebrafish MAO and the distribution of MAO mRNA and activity in zebrafish brain. The gene is located in chromosome 9 and consists of 15 exons. The amino acid composition of the active center resembles both human MAO-A and MAO-B. The enzyme displayed the highest substrate specificity for tyramine, followed by serotonin, phenylethylamine, MPTP, and dopamine; isoform-specific antagonists blocked the activity of the enzyme with equal potency. Zebrafish MAO mRNA, which was present in several tissues, and enzyme displayed differential distribution in the brain; dopaminergic cell clusters had low to moderate levels of MAO activity, whereas the highest levels of MAO activity were detected in noradrenergic and serotonergic cell groups and the habenulointerpeduncular pathway, including its caudal projection to the medial ventral rhombencephalon. The results of this study confirm the presence of functionally active MAO in zebrafish brain and other tissues and characterize the neural systems that express MAO and areas of intense activity in the brain. They also suggest that MPTP toxicity not related to MAO may affect the zebrafish brain.

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.

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

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)

Quantification and Assessment of the Chemical Form of Residual Gadolinium in the Brain After Repeated Administration of Gadolinium-Based Contrast Agents: Comparative Study in Rats.

PubMed

Frenzel, Thomas; Apte, Chirag; Jost, Gregor; Schöckel, Laura; Lohrke, Jessica; Pietsch, Hubertus

2017-07-01

Multiple clinical and preclinical studies have reported a signal intensity increase and the presence of gadolinium (Gd) in the brain after repeated administration of Gd-based contrast agents (GBCAs). This bioanalytical study in rat brain tissue was initiated to investigate whether the residual Gd is present as intact GBCA or in other chemical forms by using tissue fractionation and chromatography. Rats were divided randomly in 6 groups of 10 animals each. They received 10 daily injections of 2.5 mmol/kg bodyweight of 1 of 5 different GBCAs: linear GBCAs such as gadodiamide (Omniscan; GE Healthcare), gadopentetate dimeglumine (Gd-DTPA, Magnevist; Bayer), or gadobenate dimeglumine (Multihance; Bracco) and macrocyclic GBCAs such as gadobutrol (Gadovist; Bayer) and gadoterate meglumine (Gd-DOTA, Dotarem; Guerbet) or saline. On days 3 and 24 after the last injection (p.i.), 5 randomly chosen animals of each group were killed by exsanguination, and their brains were excised and divided into cerebrum, pons, and cerebellum. The brain sections were homogenized by sonication in ice-cold buffer at pH 7.4. Soluble and insoluble fractions were separated by centrifugation, and the soluble fractions were further separated by gel permeation chromatography (GPC). The Gd concentration in all tissue fractions and in the GPC eluate was measured by inductively coupled plasma-mass spectrometry. In a recovery control experiment, all GBCAs were spiked to blank brain tissue and more than 94% recovery of Gd in the tissue fractions was demonstrated. Only traces of the administered Gd were found in the rat brain tissue on day 3 and day 24 p.i. In the animals treated with macrocyclic GBCAs, Gd was found only in the soluble brain fraction and was present solely as low molecular weight molecules, most likely the intact GBCA. In the animals treated with linear GBCAs Gd was found to a large extent in the insoluble tissue fraction. The Gd concentration in the soluble fraction was comparable to the macrocyclic agents. According to GPC, a smaller portion of the Gd in the soluble fraction of the linear GBCAs groups was bound to macromolecules larger than 250 to 300 kDa. The nature of the Gd-containing macromolecules and the insoluble species were not determined, but they appeared to be saturable with Gd. The excretion of the soluble Gd species in the linear and macrocyclic GBCA groups was still ongoing between days 3 and 24 p.i. This was also observed for the macromolecular Gd species in the linear GBCA groups, but at a slower rate. The residual Gd found in the rat brain after repeated administration of all 3 linear GBCAs was present in at least 3 distinctive forms-soluble small molecules, including the intact GBCA, soluble macromolecules, and to a large extent in insoluble form. The latter 2 are most likely responsible for the prolonged signal intensity enhancement in brain structures observed in magnetic resonance imaging. No relevant differences between the 3 linear GBCAs were observed. The Gd concentrations in the brain after administration of macrocyclic GBCAs are lower, and the Gd is only present in soluble small molecules, which were slowly excreted. This underlines the crucial importance of the kinetic inertness of macrocyclic agents in the prevention of potential retention of Gd in the brain compared with the 3 linear, kinetically less restricted GBCAs.

Quantification and Assessment of the Chemical Form of Residual Gadolinium in the Brain After Repeated Administration of Gadolinium-Based Contrast Agents

PubMed Central

Frenzel, Thomas; Apte, Chirag; Jost, Gregor; Schöckel, Laura; Lohrke, Jessica; Pietsch, Hubertus

2017-01-01

Objective Multiple clinical and preclinical studies have reported a signal intensity increase and the presence of gadolinium (Gd) in the brain after repeated administration of Gd-based contrast agents (GBCAs). This bioanalytical study in rat brain tissue was initiated to investigate whether the residual Gd is present as intact GBCA or in other chemical forms by using tissue fractionation and chromatography. Materials and Methods Rats were divided randomly in 6 groups of 10 animals each. They received 10 daily injections of 2.5 mmol/kg bodyweight of 1 of 5 different GBCAs: linear GBCAs such as gadodiamide (Omniscan; GE Healthcare), gadopentetate dimeglumine (Gd-DTPA, Magnevist; Bayer), or gadobenate dimeglumine (Multihance; Bracco) and macrocyclic GBCAs such as gadobutrol (Gadovist; Bayer) and gadoterate meglumine (Gd-DOTA, Dotarem; Guerbet) or saline. On days 3 and 24 after the last injection (p.i.), 5 randomly chosen animals of each group were killed by exsanguination, and their brains were excised and divided into cerebrum, pons, and cerebellum. The brain sections were homogenized by sonication in ice-cold buffer at pH 7.4. Soluble and insoluble fractions were separated by centrifugation, and the soluble fractions were further separated by gel permeation chromatography (GPC). The Gd concentration in all tissue fractions and in the GPC eluate was measured by inductively coupled plasma–mass spectrometry. In a recovery control experiment, all GBCAs were spiked to blank brain tissue and more than 94% recovery of Gd in the tissue fractions was demonstrated. Results Only traces of the administered Gd were found in the rat brain tissue on day 3 and day 24 p.i. In the animals treated with macrocyclic GBCAs, Gd was found only in the soluble brain fraction and was present solely as low molecular weight molecules, most likely the intact GBCA. In the animals treated with linear GBCAs Gd was found to a large extent in the insoluble tissue fraction. The Gd concentration in the soluble fraction was comparable to the macrocyclic agents. According to GPC, a smaller portion of the Gd in the soluble fraction of the linear GBCAs groups was bound to macromolecules larger than 250 to 300 kDa. The nature of the Gd-containing macromolecules and the insoluble species were not determined, but they appeared to be saturable with Gd. The excretion of the soluble Gd species in the linear and macrocyclic GBCA groups was still ongoing between days 3 and 24 p.i. This was also observed for the macromolecular Gd species in the linear GBCA groups, but at a slower rate. Conclusions The residual Gd found in the rat brain after repeated administration of all 3 linear GBCAs was present in at least 3 distinctive forms—soluble small molecules, including the intact GBCA, soluble macromolecules, and to a large extent in insoluble form. The latter 2 are most likely responsible for the prolonged signal intensity enhancement in brain structures observed in magnetic resonance imaging. No relevant differences between the 3 linear GBCAs were observed. The Gd concentrations in the brain after administration of macrocyclic GBCAs are lower, and the Gd is only present in soluble small molecules, which were slowly excreted. This underlines the crucial importance of the kinetic inertness of macrocyclic agents in the prevention of potential retention of Gd in the brain compared with the 3 linear, kinetically less restricted GBCAs. PMID:28125438

Glucocorticoid receptor gene expression and promoter CpG modifications throughout the human brain.

PubMed

Cao-Lei, Lei; Suwansirikul, Songkiet; Jutavijittum, Prapan; Mériaux, Sophie B; Turner, Jonathan D; Muller, Claude P

2013-11-01

Glucocorticoids and the glucocorticoid (GR) and mineralocorticoid (MR) receptors have been implicated in many processes, particularly in negative feedback regulation of the hypothalamic-pituitary-adrenal axis. Epigenetically programmed GR alternative promoter usage underlies transcriptional control of GR levels, generation of GR 3' splice variants, and the overall GC response in the brain. No detailed analysis of GR first exons or GR transcript variants throughout the human brain has been reported. Therefore we investigated post mortem tissues from 28 brain regions of 5 individuals. GR first exons were expressed throughout the healthy human brain with no region-specific usage patterns. First exon levels were highly inter-correlated suggesting that they are co-regulated. GR 3' splice variants (GRα and GR-P) were equally distributed in all regions, and GRβ expression was always low. GR/MR ratios showed significant differences between the 28 tissues with the highest ratio in the pituitary gland. Modification levels of individual CpG dinucleotides, including 5-mC and 5-hmC, in promoters 1D, 1E, 1F, and 1H were low, and diffusely clustered; despite significant heterogeneity between the donors. In agreement with this clustering, sum modification levels rather than individual CpG modifications correlated with GR expression. Two-way ANOVA showed that this sum modification was both promoter and brain region specific, but that there was however no promoter*tissue interaction. The heterogeneity between donors may however hide such an interaction. In both promoters 1F and 1H modification levels correlated with GRα expression suggesting that 5-mC and 5-hmC play an important role in fine tuning GR expression levels throughout the brain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sex-specific effects of cytotoxic chemotherapy agents cyclophospha-mide and mitomycin C on gene expression, oxidative DNA damage, and epigenetic alterations in the prefrontal cortex and hippocampus – an aging connection

PubMed Central

Kovalchuk, Anna; Rodriguez-Juarez, Rocio; Ilnytskyy, Yaroslav; Byeon, Boseon; Shpyleva, Svitlana; Melnyk, Stepan; Pogribny, Igor; Kolb, Bryan; Kovalchuk, Olga

2016-01-01

Recent research shows that chemotherapy agents can be more toxic to healthy brain cells than to the target cancer cells. They cause a range of side effects, including memory loss and cognitive dysfunction that can persist long after the completion of treatment. This condition is known as chemo brain. The molecular and cellular mechanisms of chemo brain remain obscure. Here, we analyzed the effects of two cytotoxic chemotherapy drugs—cyclophosphamide (CPP) and mitomycin C (MMC) - on transcriptomic and epigenetic changes in the murine prefrontal cortex (PFC) and hippocampal regions. We for the first time showed that CPP and MMC treatments led to profound sex- and brain region-specific alterations in gene expression profiles. Gene expression changes were most prominent in the PFC tissues of female mice 3 weeks after MMC treatment, and the gene expression response was much greater for MCC than CPP exposure. MMC exposure resulted in oxidative DNA damage, evidenced by accumulation of 8-oxo-2′-deoxyguanosine (8-oxodG) and a decrease in the level of 8-oxodG repair protein OGG1 in the PFC of female animals 3 weeks after treatment. MMC treatment decreased global DNA methylation and increased DNA hydroxymethylation in the PFC tissues of female mice. The majority of the changes induced by chemotherapy in the PFC tissues of female mice resembled those that occur during the brain's aging processes. Therefore, our study suggests a link between chemotherapy-induced chemo brain and brain aging, and provides an important roadmap for future analysis. PMID:27032448

Individualized model predicts brain current flow during transcranial direct-current stimulation treatment in responsive stroke patient.

PubMed

Datta, Abhishek; Baker, Julie M; Bikson, Marom; Fridriksson, Julius

2011-07-01

Although numerous published reports have demonstrated the beneficial effects of transcranial direct-current stimulation (tDCS) on task performance, fundamental questions remain regarding the optimal electrode configuration on the scalp. Moreover, it is expected that lesioned brain tissue will influence current flow and should therefore be considered (and perhaps leveraged) in the design of individualized tDCS therapies for stroke. The current report demonstrates how different electrode configurations influence the flow of electrical current through brain tissue in a patient who responded positively to a tDCS treatment targeting aphasia. The patient, a 60-year-old man, sustained a left hemisphere ischemic stroke (lesion size = 87.42 mL) 64 months before his participation. In this study, we present results from the first high-resolution (1 mm(3)) model of tDCS in a brain with considerable stroke-related damage; the model was individualized for the patient who received anodal tDCS to his left frontal cortex with the reference cathode electrode placed on his right shoulder. We modeled the resulting brain current flow and also considered three additional reference electrode positions: right mastoid, right orbitofrontal cortex, and a "mirror" configuration with the anode over the undamaged right cortex. Our results demonstrate the profound effect of lesioned tissue on resulting current flow and the ability to modulate current pattern through the brain, including perilesional regions, through electrode montage design. The complexity of brain current flow modulation by detailed normal and pathologic anatomy suggest: (1) That computational models are critical for the rational interpretation and design of individualized tDCS stroke-therapy; and (2) These models must accurately reproduce head anatomy as shown here. Copyright © 2011 Elsevier Inc. All rights reserved.

Development of human nervous tissue upon differentiation of embryonic stem cells in three-dimensional culture.

PubMed

Preynat-Seauve, Olivier; Suter, David M; Tirefort, Diderik; Turchi, Laurent; Virolle, Thierry; Chneiweiss, Herve; Foti, Michelangelo; Lobrinus, Johannes-Alexander; Stoppini, Luc; Feki, Anis; Dubois-Dauphin, Michel; Krause, Karl Heinz

2009-03-01

Researches on neural differentiation using embryonic stem cells (ESC) require analysis of neurogenesis in conditions mimicking physiological cellular interactions as closely as possible. In this study, we report an air-liquid interface-based culture of human ESC. This culture system allows three-dimensional cell expansion and neural differentiation in the absence of added growth factors. Over a 3-month period, a macroscopically visible, compact tissue developed. Histological coloration revealed a dense neural-like neural tissue including immature tubular structures. Electron microscopy, immunochemistry, and electrophysiological recordings demonstrated a dense network of neurons, astrocytes, and oligodendrocytes able to propagate signals. Within this tissue, tubular structures were niches of cells resembling germinal layers of human fetal brain. Indeed, the tissue contained abundant proliferating cells expressing markers of neural progenitors. Finally, the capacity to generate neural tissues on air-liquid interface differed for different ESC lines, confirming variations of their neurogenic potential. In conclusion, this study demonstrates in vitro engineering of a human neural-like tissue with an organization that bears resemblance to early developing brain. As opposed to previously described methods, this differentiation (a) allows three-dimensional organization, (b) yields dense interconnected neural tissue with structurally and functionally distinct areas, and (c) is spontaneously guided by endogenous developmental cues.

[Postmortem distribution of tetrodotoxin in tissues and body fluids of guinea pigs].

PubMed

Liu, Wei; Da, Qing; Shen, Min

2012-06-01

To investigate the postmortem distribution of tetrodotoxin in tissues and body fluids of guinea pig, and to provide method and evidence for forensic identification and clinical diagnosis and treatment. Guinea pigs were intragastric administrated with 100, 50, 15 microg/kg tetrodotoxin, respectively. The poisoning symptoms were observed. The samples of heart, liver, spleen, lung, kidney, brain, stomach, intestines, bile, heart blood and urine were collected. The concentrations of tetrodotoxin in tissues and body fluids were measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS). After administrated with tetrodotoxin, all guinea pigs came out poisoning signs including tachypnea, weary and dead finally. Tetrodotoxin concentrations in lung, stomach, intestines and urine were higher, followed by blood, heart and brain. The concentration in bile was the lowest. Postmortem distribution of tetrodotoxin in guinea pig is uneven. The concentration in the lung, stomach, intestines, urine and heart blood are higher, those tissues could be used for diagnosis of tetrodotoxin poisoning.

Arsenic affects inflammatory cytokine expression in Gallus gallus brain tissues.

PubMed

Sun, Xiao; He, Ying; Guo, Ying; Li, Siwen; Zhao, Hongjing; Wang, Yu; Zhang, Jingyu; Xing, Mingwei

2017-06-05

The heavy metal arsenic is widely distributed in nature and posses a serious threat to organism's health. However, little is known about the arsenic-induced inflammatory response in the brain tissues of birds and the relationship and mechanism of the inflammatory response. The purpose of this study was to explore the effects of dietary arsenic on the expression of inflammatory cytokines in the brains of Gallus gallus. Seventy-two 1-day-old male Hy-line chickens were divided into a control group, a low arsenic trioxide (As 2 O 3 )-treated (7.5 mg/kg) group, a middle As 2 O 3 -treated (15 mg/kg) group, and a high As 2 O 3 -treated (30 mg/kg) group. Arsenic exposure caused obvious ultrastructural changes. The mRNA levels of the transcription factor nuclear factor-κB (NF-κB) and of pro-inflammatory cytokines, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E synthase (PTGEs), in chicken brain tissues (cerebrum, cerebellum, thalamus, brainstem and myelencephalon) on days 30, 60 and 90, respectively, were measured by real-time PCR. The protein expression of iNOS was detected by western blot. The results showed that after being treated with As 2 O 3, the levels of inflammatory-related factor NF-κB and pro-inflammatory cytokines in chicken brain tissues increased (P < 0.05). Arsenic exposure in the chickens triggered host defence and induced an inflammatory response by regulating the expression of inflammatory-related genes in the cerebrum, cerebellum, thalamus, brainstem and myelencephalon. These data form a foundation for further research on arsenic-induced neurotoxicity in Gallus gallus.

Transcriptomic profiling of human peritumoral neocortex tissues revealed genes possibly involved in tumor-induced epilepsy.

PubMed

Niesen, Charles E; Xu, Jun; Fan, Xuemo; Li, Xiaojin; Wheeler, Christopher J; Mamelak, Adam N; Wang, Charles

2013-01-01

The molecular mechanism underlying tumor-induced epileptogenesis is poorly understood. Alterations in the peritumoral microenvironment are believed to play a significant role in inducing epileptogenesis. We hypothesize that the change of gene expression in brain peritumoral tissues may contribute to the increased neuronal excitability and epileptogenesis. To identify the genes possibly involved in tumor-induced epilepsy, a genome-wide gene expression profiling was conducted using Affymetrix HG U133 plus 2.0 arrays and RNAs derived from formalin-fixed paraffin embedded (FFPE) peritumoral cortex tissue slides from 5-seizure vs. 5-non-seizure low grade brain tumor patients. We identified many differentially expressed genes (DEGs). Seven dysregulated genes (i.e., C1QB, CALCRL, CCR1, KAL1, SLC1A2, SSTR1 and TYRO3) were validated by qRT-PCR, which showed a high concordance. Principal Component Analysis (PCA) showed that epilepsy subjects were clustered together tightly (except one sample) and were clearly separated from the non-epilepsy subjects. Molecular functional categorization showed that significant portions of the DEGs functioned as receptor activity, molecular binding including enzyme binding and transcription factor binding. Pathway analysis showed these DEGs were mainly enriched in focal adhesion, ECM-receptor interaction, and cell adhesion molecules pathways. In conclusion, our study showed that dysregulation of gene expression in the peritumoral tissues may be one of the major mechanisms of brain tumor induced-epilepsy. However, due to the small sample size of the present study, further validation study is needed. A deeper characterization on the dysregulated genes involved in brain tumor-induced epilepsy may shed some light on the management of epilepsy due to brain tumors.

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.

Peri-tumoral leakage during intra-tumoral convection-enhanced delivery has implications for efficacy of peri-tumoral infusion before removal of tumor.

PubMed

Yang, Xiaoliang; Saito, Ryuta; Nakamura, Taigen; Zhang, Rong; Sonoda, Yukihiko; Kumabe, Toshihiro; Forsayeth, John; Bankiewicz, Krystof; Tominaga, Teiji

2016-01-01

In cases of malignant brain tumors, infiltrating tumor cells that exist at the tumor-surrounding brain tissue always escape from cytoreductive surgery and, protected by blood-brain barrier (BBB), survive the adjuvant chemoradiotherapy, eventually leading to tumor recurrence. Local interstitial delivery of chemotherapeutic agents is a promising strategy to target these cells. During our effort to develop effective drug delivery methods by intra-tumoral infusion of chemotherapeutic agents, we found consistent pattern of leakage from the tumor. Here we describe our findings and propose promising strategy to cover the brain tissue surrounding the tumor with therapeutic agents by means of convection-enhanced delivery. First, the intracranial tumor isograft model was used to define patterns of leakage from tumor mass after intra-tumoral infusion of the chemotherapeutic agents. Liposomal doxorubicin, although first distributed inside the tumor, distributed diffusely into the surrounding normal brain once the leakage happen. Trypan blue dye was used to evaluate the distribution pattern of peri-tumoral infusions. When infused intra- or peri-tumorally, infusates distributed robustly into the tumor border. Subsequently, volume of distributions with different infusion scheduling; including intra-tumoral infusion, peri-tumoral infusion after tumor resection, peri-tumoral infusion without tumor removal with or without systemic infusion of steroids, were compared with Evans-blue dye. Peri-tumoral infusion without tumor removal resulted in maximum volume of distribution. Prior use of steroids further increased the volume of distribution. Local interstitial drug delivery targeting tumor surrounding brain tissue before tumor removal should be more effective when targeting the invading cells.

Analysis of a simulation algorithm for direct brain drug delivery

PubMed Central

Rosenbluth, Kathryn Hammond; Eschermann, Jan Felix; Mittermeyer, Gabriele; Thomson, Rowena; Mittermeyer, Stephan; Bankiewicz, Krystof S.

2011-01-01

Convection enhanced delivery (CED) achieves targeted delivery of drugs with a pressure-driven infusion through a cannula placed stereotactically in the brain. This technique bypasses the blood brain barrier and gives precise distributions of drugs, minimizing off-target effects of compounds such as viral vectors for gene therapy or toxic chemotherapy agents. The exact distribution is affected by the cannula positioning, flow rate and underlying tissue structure. This study presents an analysis of a simulation algorithm for predicting the distribution using baseline MRI images acquired prior to inserting the cannula. The MRI images included diffusion tensor imaging (DTI) to estimate the tissue properties. The algorithm was adapted for the devices and protocols identified for upcoming trials and validated with direct MRI visualization of Gadolinium in 20 infusions in non-human primates. We found strong agreement between the size and location of the simulated and gadolinium volumes, demonstrating the clinical utility of this surgical planning algorithm. PMID:21945468

Advances in Light Microscopy for Neuroscience

PubMed Central

Wilt, Brian A.; Burns, Laurie D.; Ho, Eric Tatt Wei; Ghosh, Kunal K.; Mukamel, Eran A.

2010-01-01

Since the work of Golgi and Cajal, light microscopy has remained a key tool for neuroscientists to observe cellular properties. Ongoing advances have enabled new experimental capabilities using light to inspect the nervous system across multiple spatial scales, including ultrastructural scales finer than the optical diffraction limit. Other progress permits functional imaging at faster speeds, at greater depths in brain tissue, and over larger tissue volumes than previously possible. Portable, miniaturized fluorescence microscopes now allow brain imaging in freely behaving mice. Complementary progress on animal preparations has enabled imaging in head-restrained behaving animals, as well as time-lapse microscopy studies in the brains of live subjects. Mouse genetic approaches permit mosaic and inducible fluorescence-labeling strategies, whereas intrinsic contrast mechanisms allow in vivo imaging of animals and humans without use of exogenous markers. This review surveys such advances and highlights emerging capabilities of particular interest to neuroscientists. PMID:19555292

Brain size and visual environment predict species differences in paper wasp sensory processing brain regions (hymenoptera: vespidae, polistinae).

PubMed

O'Donnell, Sean; Clifford, Marie R; DeLeon, Sara; Papa, Christopher; Zahedi, Nazaneen; Bulova, Susan J

2013-01-01

The mosaic brain evolution hypothesis predicts that the relative volumes of functionally distinct brain regions will vary independently and correlate with species' ecology. Paper wasp species (Hymenoptera: Vespidae, Polistinae) differ in light exposure: they construct open versus enclosed nests and one genus (Apoica) is nocturnal. We asked whether light environments were related to species differences in the size of antennal and optic processing brain tissues. Paper wasp brains have anatomically distinct peripheral and central regions that process antennal and optic sensory inputs. We measured the volumes of 4 sensory processing brain regions in paper wasp species from 13 Neotropical genera including open and enclosed nesters, and diurnal and nocturnal species. Species differed in sensory region volumes, but there was no evidence for trade-offs among sensory modalities. All sensory region volumes correlated with brain size. However, peripheral optic processing investment increased with brain size at a higher rate than peripheral antennal processing investment. Our data suggest that mosaic and concerted (size-constrained) brain evolution are not exclusive alternatives. When brain regions increase with brain size at different rates, these distinct allometries can allow for differential investment among sensory modalities. As predicted by mosaic evolution, species ecology was associated with some aspects of brain region investment. Nest architecture variation was not associated with brain investment differences, but the nocturnal genus Apoica had the largest antennal:optic volume ratio in its peripheral sensory lobes. Investment in central processing tissues was not related to nocturnality, a pattern also noted in mammals. The plasticity of neural connections in central regions may accommodate evolutionary shifts in input from the periphery with relatively minor changes in volume. © 2013 S. Karger AG, Basel.

First multiphoton tomography of brain in man

NASA Astrophysics Data System (ADS)

König, Karsten; Kantelhardt, Sven R.; Kalasauskas, Darius; Kim, Ella; Giese, Alf

2016-03-01

We report on the first two-photon in vivo brain tissue imaging study in man. High resolution in vivo histology by multiphoton tomography (MPT) including two-photon FLIM was performed in the operation theatre during neurosurgery to evaluate the feasibility to detect label-free tumor borders with subcellular resolution. This feasibility study demonstrates, that MPT has the potential to identify tumor borders on a cellular level in nearly real-time.

Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential.

PubMed

Lojewski, Xenia; Srimasorn, Sumitra; Rauh, Juliane; Francke, Silvan; Wobus, Manja; Taylor, Verdon; Araúzo-Bravo, Marcos J; Hallmeyer-Elgner, Susanne; Kirsch, Matthias; Schwarz, Sigrid; Schwarz, Johannes; Storch, Alexander; Hermann, Andreas

2015-10-01

Brain perivascular cells have recently been identified as a novel mesodermal cell type in the human brain. These cells reside in the perivascular niche and were shown to have mesodermal and, to a lesser extent, tissue-specific differentiation potential. Mesenchymal stem cells (MSCs) are widely proposed for use in cell therapy in many neurological disorders; therefore, it is of importance to better understand the "intrinsic" MSC population of the human brain. We systematically characterized adult human brain-derived pericytes during in vitro expansion and differentiation and compared these cells with fetal and adult human brain-derived neural stem cells (NSCs) and adult human bone marrow-derived MSCs. We found that adult human brain pericytes, which can be isolated from the hippocampus and from subcortical white matter, are-in contrast to adult human NSCs-easily expandable in monolayer cultures and show many similarities to human bone marrow-derived MSCs both regarding both surface marker expression and after whole transcriptome profile. Human brain pericytes showed a negligible propensity for neuroectodermal differentiation under various differentiation conditions but efficiently generated mesodermal progeny. Consequently, human brain pericytes resemble bone marrow-derived MSCs and might be very interesting for possible autologous and endogenous stem cell-based treatment strategies and cell therapeutic approaches for treating neurological diseases. Perivascular mesenchymal stem cells (MSCs) recently gained significant interest because of their appearance in many tissues including the human brain. MSCs were often reported as being beneficial after transplantation in the central nervous system in different neurological diseases; therefore, adult brain perivascular cells derived from human neural tissue were systematically characterized concerning neural stem cell and MSC marker expression, transcriptomics, and mesodermal and inherent neuroectodermal differentiation potential in vitro and in vivo after in utero transplantation. This study showed the lack of an innate neuronal but high mesodermal differentiation potential. Because of their relationship to mesenchymal stem cells, these adult brain perivascular mesodermal cells are of great interest for possible autologous therapeutic use. ©AlphaMed Press.

Selective localization of oxytocin receptors and vasopressin 1a receptors in the human brainstem

PubMed Central

Freeman, Sara M.; Smith, Aaron L.; Goodman, Mark M.; Bales, Karen L.

2017-01-01

Intranasal oxytocin affects a suite of human social behaviors, including trust, eye contact, and emotion recognition. However, it is unclear where oxytocin receptors (OXTR) and the structurally related vasopressin 1a receptors (AVPR1a) are expressed in the human brain. We have previously described a reliable, pharmacologically informed receptor autoradiography protocol for visualizing these receptors in postmortem primate brain tissue. We used this technique in human brainstem tissue to identify the neural targets of oxytocin and vasopressin. To determine binding selectivity of the OXTR radioligand and AVPR1a radioligand, sections were incubated in four conditions: radioligand alone, radioligand with the selective AVPR1a competitor SR49059, and radioligand with a low or high concentration of the selective OXTR competitor ALS-II-69. We found selective OXTR binding in the spinal trigeminal nucleus, a conserved region of OXTR expression in all primate species investigated to date. We found selective AVPR1a binding in the nucleus prepositus, an area implicated in eye gaze stabilization. The tissue's postmortem interval was not correlated with either the specific or nonspecific binding of either radioligand, indicating that it will not likely be a factor in similar postmortem studies. This study provides critical data for future studies of OXTR and AVPR1a in human brain tissue. PMID:26911439

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.

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.

Antidepressant pharmaceuticals in two U.S. effluent-impacted streams: Occurrence and fate in water and sediment and selective uptake in fish neural tissue

USGS Publications Warehouse

Schultz, M.M.; Furlong, E.T.; Kolpin, D.W.; Werner, S.L.; Schoenfuss, H.L.; Barber, L.B.; Blazer, V.S.; Norris, D.O.; Vajda, A.M.

2010-01-01

Antidepressant pharmaceuticals are widely prescribed in the United States; release of municipal wastewater effluent is a primary route introducing them to aquatic environments, where little is known about their distribution and fate. Water, bed sediment, and brain tissue from native white suckers (Catostomus commersoni)were collected upstream and atpoints progressively downstream from outfalls discharging to two effluentimpacted streams, Boulder Creek (Colorado) and Fourmile Creek (Iowa). A liquid chromatography/tandem mass spectrometry method was used to quantify antidepressants, including fluoxetine, norfluoxetine (degradate), sertraline, norsertraline (degradate), paroxetine, Citalopram, fluvoxamine, duloxetine, venlafaxine, and bupropion in all three sample matrices. Antidepressants were not present above the limit of quantitation in water samples upstream from the effluent outfalls but were present at points downstream at ng/L concentrations, even at the farthest downstream sampling site 8.4 km downstream from the outfall. The antidepressants with the highest measured concentrations in both streams were venlafaxine, bupropion, and Citalopram and typically were observed at concentrations of at least an order of magnitude greater than the more commonly investigated antidepressants fluoxetine and sertraline. Concentrations of antidepressants in bed sediment were measured at ng/g levels; venlafaxine and fluoxetine were the predominant chemicals observed. Fluoxetine, sertraline, and their degradates were the principal antidepressants observed in fish brain tissue, typically at low ng/g concentrations. Aqualitatively different antidepressant profile was observed in brain tissue compared to streamwater samples. This study documents that wastewater effluent can be a point source of antidepressants to stream ecosystems and that the qualitative composition of antidepressants in brain tissue from exposed fish differs substantially from the compositions observed in streamwater and sediment, suggesting selective uptake. ?? 2010 American Chemical Society.

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.

Convergent roles of de novo mutations and common variants in schizophrenia in tissue-specific and spatiotemporal co-expression network.

PubMed

Jia, Peilin; Chen, Xiangning; Fanous, Ayman H; Zhao, Zhongming

2018-05-24

Genetic components susceptible to complex disease such as schizophrenia include a wide spectrum of variants, including common variants (CVs) and de novo mutations (DNMs). Although CVs and DNMs differ by origin, it remains elusive whether and how they interact at the gene, pathway, and network levels that leads to the disease. In this work, we characterized the genes harboring schizophrenia-associated CVs (CVgenes) and the genes harboring DNMs (DNMgenes) using measures from network, tissue-specific expression profile, and spatiotemporal brain expression profile. We developed an algorithm to link the DNMgenes and CVgenes in spatiotemporal brain co-expression networks. DNMgenes tended to have central roles in the human protein-protein interaction (PPI) network, evidenced in their high degree and high betweenness values. DNMgenes and CVgenes connected with each other significantly more often than with other genes in the networks. However, only CVgenes remained significantly connected after adjusting for their degree. In our gene co-expression PPI network, we found DNMgenes and CVgenes connected in a tissue-specific fashion, and such a pattern was similar to that in GTEx brain but not in other GTEx tissues. Importantly, DNMgene-CVgene subnetworks were enriched with pathways of chromatin remodeling, MHC protein complex binding, and neurotransmitter activities. In summary, our results unveiled that both DNMgenes and CVgenes contributed to a core set of biologically important pathways and networks, and their interactions may attribute to the risk for schizophrenia. Our results also suggested a stronger biological effect of DNMgenes than CVgenes in schizophrenia.

Brain Metal Distribution and Neuro-Inflammatory Profiles after Chronic Vanadium Administration and Withdrawal in Mice

PubMed Central

Folarin, Oluwabusayo R.; Snyder, Amanda M.; Peters, Douglas G.; Olopade, Funmilayo; Connor, James R.; Olopade, James O.

2017-01-01

Vanadium is a potentially toxic environmental pollutant and induces oxidative damage in biological systems including the central nervous system (CNS). Its deposition in brain tissue may be involved in the pathogenesis of certain neurological disorders which after prolonged exposure can culminate into more severe pathology. Most studies on vanadium neurotoxicity have been done after acute exposure but in reality some populations are exposed for a lifetime. This work was designed to ascertain neurodegenerative consequences of chronic vanadium administration and to investigate the progressive changes in the brain after withdrawal from vanadium treatment. A total of 85 male BALB/c mice were used for the experiment and divided into three major groups of vanadium treated (intraperitoneally (i.p.) injected with 3 mg/kg body weight of sodium metavanadate and sacrificed every 3 months till 18 months); matched controls; and animals that were exposed to vanadium for 3 months and thereafter the metal was withdrawn. Brain tissues were obtained after animal sacrifice. Sagittal cut sections of paraffin embedded tissue (5 μm) were analyzed by the Laser ablation-inductively coupled plasma-mass spectrometry (LA–ICP–MS) to show the absorption and distribution of vanadium metal. Also, Haematoxylin and Eosin (H&E) staining of brain sections, and immunohistochemistry for Microglia (Iba-1), Astrocytes (GFAP), Neurons (Neu-N) and Neu-N + 4′,6-diamidine-2′-pheynylindole dihydrochloride (Dapi) Immunofluorescent labeling were observed for morphological and morphometric parameters. The LA–ICP–MS results showed progressive increase in vanadium uptake with time in different brain regions with prediction for regions like the olfactory bulb, brain stem and cerebellum. The withdrawal brains still show presence of vanadium metal in the brain slightly more than the controls. There were morphological alterations (of the layering profile, nuclear shrinkage) in the prefrontal cortex, cellular degeneration (loss of dendritic arborization) and cell death in the Hippocampal CA1 pyramidal cells and Purkinje cells of the cerebellum, including astrocytic and microglial activation in vanadium exposed brains which were all attenuated in the withdrawal group. With exposure into old age, the evident neuropathology was microgliosis, while progressive astrogliosis became more attenuated. We have shown that chronic administration of vanadium over a lifetime in mice resulted in metal accumulation which showed regional variabilities with time. The metal profile and pathological effects were not completely eliminated from the brain even after a long time withdrawal from vanadium metal. PMID:28790895

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.

Monitoring Dopamine ex Vivo during Electrical Stimulation Using Liquid-Microjunction Surface Sampling.

PubMed

Gill, Emily L; Marks, Megan; Yost, Richard A; Vedam-Mai, Vinata; Garrett, Timothy J

2017-12-19

Liquid-microjunction surface sampling (LMJ-SS) is an ambient ionization technique based on the continuous flow of solvent using an in situ microextraction device in which solvent moves through the probe, drawing in the analytes in preparation for ionization using an electrospray ionization source. However, unlike traditional mass spectrometry (MS) techniques, it operates under ambient pressure and requires no sample preparation, thereby making it ideal for rapid sampling of thicker tissue sections for electrophysiological and other neuroscientific research studies. Studies interrogating neural synapses, or a specific neural circuit, typically employ thick, ex vivo tissue sections maintained under near-physiological conditions to preserve tissue viability and maintain the neural networks. Deep brain stimulation (DBS) is a surgical procedure used to treat the neurological symptoms that are associated with certain neurodegenerative and neuropsychiatric diseases. Parkinson's disease (PD) is a neurological disorder which is commonly treated with DBS therapy. PD is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta portion of the brain. Here, we demonstrate that the LMJ-SS methodology can provide a platform for ex vivo analysis of the brain during electrical stimulation, such as DBS. We employ LMJ-SS in the ex vivo analysis of mouse brain tissue for monitoring dopamine during electrical stimulation of the striatum region. The mouse brain tissue was sectioned fresh post sacrifice and maintained in artificial cerebrospinal fluid to create near-physiological conditions before direct sampling using LMJ-SS. A selection of metabolites, including time-sensitive metabolites involved in energy regulation in the brain, were identified using standards, and the mass spectral database mzCloud was used to assess the feasibility of the methodology. Thereafter, the intensity of m/z 154 corresponding to protonated dopamine was monitored before and after electrical stimulation of the striatum region, showing an increase in signal directly following a stimulation event. Dopamine is the key neurotransmitter implicated in PD, and although electrochemical detectors have shown such increases in dopamine post-DBS, this is the first study to do so using MS methodologies.

Primary blast-induced traumatic brain injury: lessons from lithotripsy

NASA Astrophysics Data System (ADS)

Nakagawa, A.; Ohtani, K.; Armonda, R.; Tomita, H.; Sakuma, A.; Mugikura, S.; Takayama, K.; Kushimoto, S.; Tominaga, T.

2017-11-01

Traumatic injury caused by explosive or blast events is traditionally divided into four mechanisms: primary, secondary, tertiary, and quaternary blast injury. The mechanisms of blast-induced traumatic brain injury (bTBI) are biomechanically distinct and can be modeled in both in vivo and in vitro systems. The primary bTBI injury mechanism is associated with the response of brain tissue to the initial blast wave. Among the four mechanisms of bTBI, there is a remarkable lack of information regarding the mechanism of primary bTBI. On the other hand, 30 years of research on the medical application of shock waves (SWs) has given us insight into the mechanisms of tissue and cellular damage in bTBI, including both air-mediated and underwater SW sources. From a basic physics perspective, the typical blast wave consists of a lead SW followed by shock-accelerated flow. The resultant tissue injury includes several features observed in primary bTBI, such as hemorrhage, edema, pseudo-aneurysm formation, vasoconstriction, and induction of apoptosis. These are well-described pathological findings within the SW literature. Acoustic impedance mismatch, penetration of tissue by shock/bubble interaction, geometry of the skull, shear stress, tensile stress, and subsequent cavitation formation are all important factors in determining the extent of SW-induced tissue and cellular injury. In addition, neuropsychiatric aspects of blast events need to be taken into account, as evidenced by reports of comorbidity and of some similar symptoms between physical injury resulting in bTBI and the psychiatric sequelae of post-traumatic stress. Research into blast injury biophysics is important to elucidate specific pathophysiologic mechanisms of blast injury, which enable accurate differential diagnosis, as well as development of effective treatments. Herein we describe the requirements for an adequate experimental setup when investigating blast-induced tissue and cellular injury; review SW physics, research, and the importance of engineering validation (visualization/pressure measurement/numerical simulation); and, based upon our findings of SW-induced injury, discuss the potential underlying mechanisms of primary bTBI.

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

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.

A method for evaluating nanoparticle transport through the blood-brain barrier in vitro.

PubMed

Guarnieri, Daniela; Muscetti, Ornella; Netti, Paolo A

2014-01-01

Blood-brain barrier (BBB) represents a formidable barrier for many therapeutic drugs to enter the brain tissue. The development of new strategies for enhancing drug delivery to the brain is of great importance in diagnostics and therapeutics of central nervous system (CNS) diseases. In this context, nanoparticles are an emerging class of drug delivery systems that can be easily tailored to deliver drugs to various compartments of the body, including the brain. To identify, characterize, and validate novel nanoparticles applicable to brain delivery, in vitro BBB model systems have been developed. In this work, we describe a method to screen nanoparticles with variable size and surface functionalization in order to define the physicochemical characteristics underlying the design of nanoparticles that are able to efficiently cross the BBB.

Hyperbaric oxygen therapy ameliorates acute brain injury after porcine intracerebral hemorrhage at high altitude.

PubMed

Zhu, Hai-tao; Bian, Chen; Yuan, Ji-chao; Liao, Xiao-jun; Liu, Wei; Zhu, Gang; Feng, Hua; Lin, Jiang-kai

2015-06-15

Intracerebral hemorrhage (ICH) at high altitude is not well understood to date. This study investigates the effects of high altitude on ICH, and examines the acute neuroprotection of hyperbaric oxygen (HBO) therapy against high-altitude ICH. Minipigs were placed in a hypobaric chamber for 72 h before the operation. ICH was induced by an infusion of autologous arterial blood (3 ml) into the right basal ganglia. Animals in the high-altitude ICH group received HBO therapy (2.5 ATA for 60 min) 30 min after ICH. Blood gas, blood glucose and brain tissue oxygen partial pressure (PbtO2) were monitored continuously for animals from all groups, as were microdialysis products including glucose, lactate, pyruvate and glutamate in perihematomal tissue from 3 to 12 h post-ICH. High-altitude ICH animals showed significantly lower PbtO2, higher lactate/pyruvate ratio (LPR) and glutamate levels than low-altitude ICH animals. More severe neurological deficits, brain edema and neuronal damage were also observed in high-altitude ICH. After HBO therapy, PbtO2 was significantly increased and LPR and glutamate levels were significantly decreased. Brain edema, neurological deficits and neuronal damage were also ameliorated. The data suggested a more serious disturbance of tissue oxygenation and cerebral metabolism in the acute stage after ICH at high altitude. Early HBO treatment reduced acute brain injury, perhaps through a mechanism involving the amelioration of the derangement of cerebral oxygenation and metabolism following high-altitude ICH.

Chemical imaging analysis of the brain with X-ray methods

NASA Astrophysics Data System (ADS)

Collingwood, Joanna F.; Adams, Freddy

2017-04-01

Cells employ various metal and metalloid ions to augment the structure and the function of proteins and to assist with vital biological processes. In the brain they mediate biochemical processes, and disrupted metabolism of metals may be a contributing factor in neurodegenerative disorders. In this tutorial review we will discuss the particular role of X-ray methods for elemental imaging analysis of accumulated metal species and metal-containing compounds in biological materials, in the context of post-mortem brain tissue. X-rays have the advantage that they have a short wavelength and can penetrate through a thick biological sample. Many of the X-ray microscopy techniques that provide the greatest sensitivity and specificity for trace metal concentrations in biological materials are emerging at synchrotron X-ray facilities. Here, the extremely high flux available across a wide range of soft and hard X-rays, combined with state-of-the-art focusing techniques and ultra-sensitive detectors, makes it viable to undertake direct imaging of a number of elements in brain tissue. The different methods for synchrotron imaging of metals in brain tissues at regional, cellular, and sub-cellular spatial resolution are discussed. Methods covered include X-ray fluorescence for elemental imaging, X-ray absorption spectrometry for speciation imaging, X-ray diffraction for structural imaging, phase contrast for enhanced contrast imaging and scanning transmission X-ray microscopy for spectromicroscopy. Two- and three-dimensional (confocal and tomographic) imaging methods are considered as well as the correlation of X-ray microscopy with other imaging tools.

A model for brain life history evolution.

PubMed

González-Forero, Mauricio; Faulwasser, Timm; Lehmann, Laurent

2017-03-01

Complex cognition and relatively large brains are distributed across various taxa, and many primarily verbal hypotheses exist to explain such diversity. Yet, mathematical approaches formalizing verbal hypotheses would help deepen the understanding of brain and cognition evolution. With this aim, we combine elements of life history and metabolic theories to formulate a metabolically explicit mathematical model for brain life history evolution. We assume that some of the brain's energetic expense is due to production (learning) and maintenance (memory) of energy-extraction skills (or cognitive abilities, knowledge, information, etc.). We also assume that individuals use such skills to extract energy from the environment, and can allocate this energy to grow and maintain the body, including brain and reproductive tissues. The model can be used to ask what fraction of growth energy should be allocated at each age, given natural selection, to growing brain and other tissues under various biological settings. We apply the model to find uninvadable allocation strategies under a baseline setting ("me vs nature"), namely when energy-extraction challenges are environmentally determined and are overcome individually but possibly with maternal help, and use modern-human data to estimate model's parameter values. The resulting uninvadable strategies yield predictions for brain and body mass throughout ontogeny and for the ages at maturity, adulthood, and brain growth arrest. We find that: (1) a me-vs-nature setting is enough to generate adult brain and body mass of ancient human scale and a sequence of childhood, adolescence, and adulthood stages; (2) large brains are favored by intermediately challenging environments, moderately effective skills, and metabolically expensive memory; and (3) adult skill is proportional to brain mass when metabolic costs of memory saturate the brain metabolic rate allocated to skills.

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

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.

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.

Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

The Neuro-Oncology Branch (NOB), Center for Cancer Research (CCR), National Cancer Institute (NCI) of the National Institutes of Health (NIH) is seeking outstanding postdoctoral candidates interested in studying the metabolic changes in brain tumors such as glioblastoma multiforme (GBMs).  NOB’s Metabolomics program is interested in revealing the metabolic alterations of isocitrate dehydrogenase (IDH1)-mutated GBMs and in exploiting these deregulations for therapeutic applications.  A combination of methods such as molecular biology, animal models, as well as in vitro and in vivo metabolomics using Raman Imaging Microscopy, Nuclear Magnetic Resonance spectroscopy (NMR), Mass Spectrometry (MS) and Magnetic Resonance Imaging (MRI) techniques are employed.  The position will specifically focus on molecular biology and Raman Imaging Microscopy, which includes work in Western Blotting, mammalian cell culture and other common biomedical techniques used in cancer bio  logy labs such as handling tissue samples, preparing tissue slides, staining, and extracting proteins from brain tissue.

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

Blood flow

MedlinePlus Videos and Cool Tools

As the heart pumps, the arteries carry oxygen-rich blood (shown in red) away from the heart and toward the body's tissues and vital organs. ... brain, liver, kidneys, stomach, and muscles, including the heart muscle itself. At the same time, the veins ...

Stability of Bovine viral diarrhea virus 1 nucleic acid in fetal bovine samples stored under different conditions.

PubMed

Ridpath, Julia F; Neill, John D; Chiang, Yu-Wei; Waldbillig, Jill

2014-01-01

Infection of pregnant cattle with both species of Bovine viral diarrhea virus (BVDV) can result in reproductive disease that includes fetal reabsorption, mummification, abortion, stillbirths, congenital defects affecting structural, neural, reproductive, and immune systems, and the birth of calves persistently infected with BVDV. Accurate diagnosis of BVDV-associated reproductive disease is important to control BVDV at the production unit level and assessment of the cost of BVDV infections in support of BVDV control programs. The purpose of the current study was to examine the stability of viral nucleic acid in fetal tissues exposed to different conditions, as measured by detection by polymerase chain reaction. Five different types of fetal tissue, including brain, skin and muscle, ear, and 2 different pooled organ samples, were subjected to conditions that mimicked those that might exist for samples collected after abortions in production settings or possible storage conditions after collection and prior to testing. In addition, tissues were archived for 36 months at -20°C and then retested, to mimic conditions that might occur in the case of retrospective surveillance studies. Brain tissue showed the highest stability under the conditions tested. The impact of fecal contamination was increased following archiving in all tissue types suggesting that, for long-term storage, effort should be made to reduce environmental contaminants before archiving.

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.

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.

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.

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.

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.

Sex-specific differences in transcriptome profiles of brain and muscle tissue of the tropical gar.

PubMed

Cribbin, Kayla M; Quackenbush, Corey R; Taylor, Kyle; Arias-Rodriguez, Lenin; Kelley, Joanna L

2017-04-07

The tropical gar (Atractosteus tropicus) is the southernmost species of the seven extant species of gar fishes in the world. In Mexico and Central America, the species is an important food source due to its nutritional quality and low price. Despite its regional importance and increasing concerns about overexploitation and habitat degradation, basic genetic information on the tropical gar is lacking. Determining genetic information on the tropical gar is important for the sustainable management of wild populations, implementation of best practices in aquaculture settings, evolutionary studies of ancient lineages, and an understanding of sex-specific gene expression. In this study, the transcriptome of the tropical gar was sequenced and assembled de novo using tissues from three males and three females using Illumina sequencing technology. Sex-specific and highly differentially expressed transcripts in brain and muscle tissues between adult males and females were subsequently identified. The transcriptome was assembled de novo resulting in 80,611 transcripts with a contig N50 of 3,355 base pairs and over 168 kilobases in total length. Male muscle, brain, and gonad as well as female muscle and brain were included in the assembly. The assembled transcriptome was annotated to identify the putative function of expressed transcripts using Trinotate and SwissProt, a database of well-annotated proteins. The brain and muscle datasets were then aligned to the assembled transcriptome to identify transcripts that were differentially expressed between males and females. The contrast between male and female brain identified 109 transcripts from 106 genes that were significantly differentially expressed. In the muscle comparison, 82 transcripts from 80 genes were identified with evidence for significant differential expression. Almost all genes identified as differentially expressed were sex-specific. The differentially expressed transcripts were enriched for genes involved in cellular functioning, signaling, immune response, and tissue-specific functions. This study identified differentially expressed transcripts between male and female gar in muscle and brain tissue. The majority of differentially expressed transcripts had sex-specific expression. Expanding on these findings to other developmental stages, populations, and species may lead to the identification of genetic factors contributing to the skewed sex ratio seen in the tropical gar and of sex-specific differences in expression in other species. Finally, the transcriptome assembly will open future research avenues on tropical gar development, cell function, environmental resistance, and evolution in the context of other early vertebrates.

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

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.

Gallic acid improved behavior, brain electrophysiology, and inflammation in a rat model of traumatic brain injury.

PubMed

Sarkaki, Alireza; Farbood, Yaghoub; Gharib-Naseri, Mohammad Kazem; Badavi, Mohammad; Mansouri, Mohammad Taghi; Haghparast, Abbas; Mirshekar, Mohammad Ali

2015-08-01

Traumatic brain injury (TBI) is one of the main causes of intellectual and cognitive disabilities. In the clinic it is essential to limit the development of cognitive impairment after TBI. In this study, the effects of gallic acid (GA; 100 mg/kg, per oral, from 7 days before to 2 days after TBI induction) on neurological score, passive avoidance memory, long-term potentiation (LTP) deficits, and levels of proinflammatory cytokines including interleukin-1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) in the brain have been evaluated. Brain injury was induced following Marmarou's method. Data were analyzed by one-way and repeated measures ANOVA followed by Tukey's post-hoc test. The results indicated that memory was significantly impaired (p < 0.001) in the group treated with TBI + vehicle, together with deterioration of the hippocampal LTP and increased brain tissue levels of IL-1β, IL-6, and TNF-α. GA treatment significantly improved memory and LTP in the TBI rats. The brain tissue levels of IL-1β, IL-6, and TNF-α were significantly reduced (p < 0.001) in the group treated with GA. The results suggest that GA has neuroprotective properties against TBI-induced behavioral, electrophysiological, and inflammatory disorders, probably via the decrease of cerebral proinflammatory cytokines.

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...

Impedance Spectrum in Cortical Tissue: Implications for Propagation of LFP Signals on the Microscopic Level

PubMed Central

Miceli, Stéphanie

2017-01-01

Brain research investigating electrical activity within neural tissue is producing an increasing amount of physiological data including local field potentials (LFPs) obtained via extracellular in vivo and in vitro recordings. In order to correctly interpret such electrophysiological data, it is vital to adequately understand the electrical properties of neural tissue itself. An ongoing controversy in the field of neuroscience is whether such frequency-dependent effects bias LFP recordings and affect the proper interpretation of the signal. On macroscopic scales and with large injected currents, previous studies have found various grades of frequency dependence of cortical tissue, ranging from negligible to strong, within the frequency band typically considered relevant for neuroscience (less than a few thousand hertz). Here, we performed a detailed investigation of the frequency dependence of the conductivity within cortical tissue at microscopic distances using small current amplitudes within the typical (neuro)physiological micrometer and sub-nanoampere range. We investigated the propagation of LFPs, induced by extracellular electrical current injections via patch-pipettes, in acute rat brain slice preparations containing the somatosensory cortex in vitro using multielectrode arrays. Based on our data, we determined the cortical tissue conductivity over a 100-fold increase in signal frequency (5–500 Hz). Our results imply at most very weak frequency-dependent effects within the frequency range of physiological LFPs. Using biophysical modeling, we estimated the impact of different putative impedance spectra. Our results indicate that frequency dependencies of the order measured here and in most other studies have negligible impact on the typical analysis and modeling of LFP signals from extracellular brain recordings. PMID:28197543

Impedance Spectrum in Cortical Tissue: Implications for Propagation of LFP Signals on the Microscopic Level.

PubMed

Miceli, Stéphanie; Ness, Torbjørn V; Einevoll, Gaute T; Schubert, Dirk

2017-01-01

Brain research investigating electrical activity within neural tissue is producing an increasing amount of physiological data including local field potentials (LFPs) obtained via extracellular in vivo and in vitro recordings. In order to correctly interpret such electrophysiological data, it is vital to adequately understand the electrical properties of neural tissue itself. An ongoing controversy in the field of neuroscience is whether such frequency-dependent effects bias LFP recordings and affect the proper interpretation of the signal. On macroscopic scales and with large injected currents, previous studies have found various grades of frequency dependence of cortical tissue, ranging from negligible to strong, within the frequency band typically considered relevant for neuroscience (less than a few thousand hertz). Here, we performed a detailed investigation of the frequency dependence of the conductivity within cortical tissue at microscopic distances using small current amplitudes within the typical (neuro)physiological micrometer and sub-nanoampere range. We investigated the propagation of LFPs, induced by extracellular electrical current injections via patch-pipettes, in acute rat brain slice preparations containing the somatosensory cortex in vitro using multielectrode arrays. Based on our data, we determined the cortical tissue conductivity over a 100-fold increase in signal frequency (5-500 Hz). Our results imply at most very weak frequency-dependent effects within the frequency range of physiological LFPs. Using biophysical modeling, we estimated the impact of different putative impedance spectra. Our results indicate that frequency dependencies of the order measured here and in most other studies have negligible impact on the typical analysis and modeling of LFP signals from extracellular brain recordings.

Contaminants of legacy and emerging concern in largescale suckers (Catostomus macrocheilus) and the foodweb in the lower Columbia River, Oregon and Washington, USA.

PubMed

Nilsen, Elena; Zaugg, Steven; Alvarez, David; Morace, Jennifer; Waite, Ian; Counihan, Timothy; Hardiman, Jill; Torres, Leticia; Patiño, Reynaldo; Mesa, Matthew; Grove, Robert

2014-06-15

We investigated occurrence, transport pathways, and effects of polybrominated diphenyl ether (PBDE) flame retardants and other endocrine disrupting chemicals (EDCs) in aquatic media and the foodweb in the lower Columbia River. In 2009 and 2010, foodweb sampling at three sites along a gradient of contaminant exposure near Skamania (Washington), Columbia City (Oregon) and Longview (Washington) included water (via passive samplers), bed sediment, invertebrate biomass residing in sediment, a resident fish species (largescale suckers [Catostomus macrocheilus]), and eggs from osprey (Pandion haliaetus). This paper primarily reports fish tissue concentrations. In 2009, composites of fish brain, fillet, liver, stomach, and gonad tissues revealed that overall contaminant concentrations were highest in livers, followed by brain, stomach, gonad, and fillet. Concentrations of halogenated compounds in tissue samples from all three sites ranged from <1 to 400nanograms per gram of wet tissue. Several chemical classes, including PBDEs, organochlorine pesticides, and polychlorinated biphenyls (PCBs), were detected at all sites and in nearly all fish tissues sampled. In 2010, only fish livers were sampled and inter-site concentration differences were not as pronounced as in 2009. Chemical concentrations in sediments, fish tissues, and osprey eggs increased moving downstream from Skamania to the urbanized sites near Columbia City and Longview. Numerous organochlorine (OC) pesticides, both banned and currently used, and PBDEs, were present at each site in multiple media and concentrations exceeded environmental quality benchmarks in some cases. Frequently detected OC compounds included hexachlorobenzene, pentachloroanisole, dichlorodiphenyltrichloroethane (DDT) and its degradates, chlorpyrifos, and oxyfluorofen. Biomagnification of BDE47, 100, 153, and 154 occurred in largescale suckers and osprey eggs. Results support the hypothesis that contaminants in the environment lead to bioaccumulation and potential negative effects in multiple levels of the foodweb. Published by Elsevier B.V.

Contaminants of legacy and emerging concern in largescale suckers (Catostomus macrocheilus) and the foodweb in the lower Columbia River, Oregon and Washington, USA

USGS Publications Warehouse

Nilsen, Elena B.; Zaugg, Steven D.; Alvarez, David A.; Morace, Jennifer L.; Waite, Ian R.; Counihan, Timothy D.; Hardiman, Jill M.; Torres, Leticia; Patino, Reynaldo; Mesa, Matthew G.; Grove, Robert

2014-01-01

We investigated occurrence, transport pathways, and effects of polybrominated diphenyl ether (PBDE) flame retardants and other endocrine disrupting chemicals (EDCs) in aquatic media and the foodweb in the lower Columbia River. In 2009 and 2010, foodweb sampling at three sites along a gradient of contaminant exposure near Skamania (Washington), Columbia City (Oregon) and Longview (Washington) included water (via passive samplers), bed sediment, invertebrate biomass residing in sediment, a resident fish species (largescale suckers [Catostomus macrocheilus]), and eggs from osprey (Pandion haliaetus). This paper primarily reports fish tissue concentrations. In 2009, composites of fish brain, fillet, liver, stomach, and gonad tissues revealed that overall contaminant concentrations were highest in livers, followed by brain, stomach, gonad, and fillet. Concentrations of halogenated compounds in tissue samples from all three sites ranged from < 1 to 400 nanograms per gram of wet tissue. Several chemical classes, including PBDEs, organochlorine pesticides, and polychlorinated biphenyls (PCBs), were detected at all sites and in nearly all fish tissues sampled. In 2010, only fish livers were sampled and inter-site concentration differences were not as pronounced as in 2009. Chemical concentrations in sediments, fish tissues, and osprey eggs increased moving downstream from Skamania to the urbanized sites near Columbia City and Longview. Numerous organochlorine (OC) pesticides, both banned and currently used, and PBDEs, were present at each site in multiple media and concentrations exceeded environmental quality benchmarks in some cases. Frequently detected OC compounds included hexachlorobenzene, pentachloroanisole, dichlorodiphenyltrichloroethane (DDT) and its degradates, chlorpyrifos, and oxyfluorofen. Biomagnification of BDE47, 100, 153, and 154 occurred in largescale suckers and osprey eggs. Results support the hypothesis that contaminants in the environment lead to bioaccumulation and potential negative effects in multiple levels of the foodweb.

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.

Adaptive optical microscope for brain imaging in vivo

NASA Astrophysics Data System (ADS)

Wang, Kai

2017-04-01

The optical heterogeneity of biological tissue imposes a major limitation to acquire detailed structural and functional information deep in the biological specimens using conventional microscopes. To restore optimal imaging performance, we developed an adaptive optical microscope based on direct wavefront sensing technique. This microscope can reliably measure and correct biological samples induced aberration. We demonstrated its performance and application in structural and functional brain imaging in various animal models, including fruit fly, zebrafish and mouse.

Perspectives and new aspects of metalloproteinases' inhibitors in therapy of CNS disorders: from chemistry to medicine.

PubMed

Boguszewska-Czubara, Anna; Budzynska, Barbara; Skalicka-Wozniak, Krystyna; Kurzepa, Jacek

2018-05-13

Matrix metalloproteinases (MMPs) play a key role in remodelling of the extracellular matrix (ECM) and, at the same time, influence cell differentiation, migration, proliferation and survival. Their importance in variety of human diseases including cancer, rheumatoid arthritis, pulmonary emphysema and fibrotic disorders has been known for many years but special attention should be paid on the role of MMPs in the central nervous system (CNS) disorders. Till now, there are not many well documented physiological MMP target proteins in the brain and only some pathological ones. Numerous neurodegenerative diseases is a consequence or result in disturbed remodeling of brain ECM, therefore proper action of MMPs as well as control of their activity may play crucial roles in the development and the progress of these diseases. In present review we discuss the role of metalloproteinase inhibitors, from the well-known natural endogenous tissue inhibitors of metalloproteinases (TIMPs) through exogenous synthetic ones like (4-phenoxyphenylsulfonyl)methylthiirane (SB-3CT), tetracyclines, batimastat (BB-94) and FN-439. As the MMP-TIMP system has been well described in physiological development as well as in pathological conditions mainly in neoplasctic diseases, the knowledge about the enzymatic system in mammalian brain tissue remain still poorly understood in this context. Therefore, we focus on MMPs inhibition in the context of physiological function of adult brain as well as pathological conditions including neurodegenerative diseases, brain injuries and others. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A model for brain life history evolution

PubMed Central

Lehmann, Laurent

2017-01-01

Complex cognition and relatively large brains are distributed across various taxa, and many primarily verbal hypotheses exist to explain such diversity. Yet, mathematical approaches formalizing verbal hypotheses would help deepen the understanding of brain and cognition evolution. With this aim, we combine elements of life history and metabolic theories to formulate a metabolically explicit mathematical model for brain life history evolution. We assume that some of the brain’s energetic expense is due to production (learning) and maintenance (memory) of energy-extraction skills (or cognitive abilities, knowledge, information, etc.). We also assume that individuals use such skills to extract energy from the environment, and can allocate this energy to grow and maintain the body, including brain and reproductive tissues. The model can be used to ask what fraction of growth energy should be allocated at each age, given natural selection, to growing brain and other tissues under various biological settings. We apply the model to find uninvadable allocation strategies under a baseline setting (“me vs nature”), namely when energy-extraction challenges are environmentally determined and are overcome individually but possibly with maternal help, and use modern-human data to estimate model’s parameter values. The resulting uninvadable strategies yield predictions for brain and body mass throughout ontogeny and for the ages at maturity, adulthood, and brain growth arrest. We find that: (1) a me-vs-nature setting is enough to generate adult brain and body mass of ancient human scale and a sequence of childhood, adolescence, and adulthood stages; (2) large brains are favored by intermediately challenging environments, moderately effective skills, and metabolically expensive memory; and (3) adult skill is proportional to brain mass when metabolic costs of memory saturate the brain metabolic rate allocated to skills. PMID:28278153

Influence of peptide transporter 2 (PEPT2) on the distribution of cefadroxil in mouse brain: A microdialysis study.

PubMed

Chen, Xiaomei; Keep, Richard F; Liang, Yan; Zhu, Hao-Jie; Hammarlund-Udenaes, Margareta; Hu, Yongjun; Smith, David E

2017-05-01

Peptide transporter 2 (PEPT2) is a high-affinity low-capacity transporter belonging to the proton-coupled oligopeptide transporter family. Although many aspects of PEPT2 structure-function are known, including its localization in choroid plexus and neurons, its regional activity in brain, especially extracellular fluid (ECF), is uncertain. In this study, the pharmacokinetics and regional brain distribution of cefadroxil, a β-lactam antibiotic and PEPT2 substrate, were investigated in wildtype and Pept2 null mice using in vivo intracerebral microdialysis. Cefadroxil was infused intravenously over 4h at 0.15mg/min/kg, and samples obtained from plasma, brain ECF, cerebrospinal fluid (CSF) and brain tissue. A permeability-surface area experiment was also performed in which 0.15mg/min/kg cefadroxil was infused intravenously for 10min, and samples obtained from plasma and brain tissues. Our results showed that PEPT2 ablation significantly increased the brain ECF and CSF levels of cefadroxil (2- to 2.5-fold). In contrast, there were no significant differences between wildtype and Pept2 null mice in the amount of cefadroxil in brain cells. The unbound volume of distribution of cefadroxil in brain was 60% lower in Pept2 null mice indicating an uptake function for PEPT2 in brain cells. Finally, PEPT2 did not affect the influx clearance of cefadroxil, thereby, ruling out differences between the two genotypes in drug entry across the blood-brain barriers. These findings demonstrate, for the first time, the impact of PEPT2 on brain ECF as well as the known role of PEPT2 in removing peptide-like drugs, such as cefadroxil, from the CSF to blood. Copyright © 2017 Elsevier Inc. All rights reserved.

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

[Effect of phospholipids containing omega-3 fatty acids on structural changes of microsomal lipids in cell membranes of functionally different cells].

PubMed

Datsenko, Z M; Volkov, H L; Kryvenko, O M; Nechytaĭlo, L O; Shovkun, S A; Khmel', T O; Perederiĭ, O F

2002-01-01

As a result of the experimental researches conducted it has been shown that administration of some normal animal marine phospholipids (PL) including in their structure omega-3 polyunsaturated fatty acids (PUFA) provides for quantitative changes of individual PL, fatty acids (FA) content and quantity in general and individual PL of liver, heart, brain and gonads microsomes. While estimating general microsomal PL fraction FA content under the action of PL omega-3 PUFA FA concentration change, unsaturation index (omega 6/omega 3) and relation of arachidonic acid to docosahexenic (AA/DHA) decrease have been identified. The decrease of AA/DHA relationship occurs due to AA and DHA quantitative changes. In the case of AA increase in some tissues there is observed the decrease of docosapentaenic acid and increase of DHA and eucosapentaenic (EPA) acidds. As a result of studying FA content in the individual PL composition it has been identified that certain PL classes characteristic for some tissues respond by changes of some certain FA. The relationship omega 6/omega 3 has been shown as decreasing in phosphatidilcholine (PC) all tissues microsomes (liver, gonads, heart, brain), in phosphatidilethanolamine (PEA) of liver and cardiac microsomes, in phosphatidilserine (PS) this relationship relationship decreases in the liver, brain and heart, for phosphatidilinositole (PI) the changes take place in liver, gonads, brain. Simultaneously, the decrease of AA/DHA relationship in the individual PL decrease of AA and increase of EPA and DHA depend on the tested tissues. The marine phospholipids might be supposed to render their effect on AA metabolism resulting in AA/DHA relationship in PEA and PS relationship displays itself as specific and depends on the tissues functions. The preference of PEA and PS use by certain tissues microsomes could be explained by their membrane protective capability.

Trace elements during primordial plexiform network formation in human cerebral organoids

PubMed Central

Sartore, Rafaela C.; Cardoso, Simone C.; Lages, Yury V.M.; Paraguassu, Julia M.; Stelling, Mariana P.; Madeiro da Costa, Rodrigo F.; Guimaraes, Marilia Z.; Pérez, Carlos A.

2017-01-01

Systematic studies of micronutrients during brain formation are hindered by restrictions to animal models and adult post-mortem tissues. Recently, advances in stem cell biology have enabled recapitulation of the early stages of human telencephalon development in vitro. In the present work, we analyzed cerebral organoids derived from human pluripotent stem cells by synchrotron radiation X-ray fluorescence in order to measure biologically valuable micronutrients incorporated and distributed into the exogenously developing brain. Our findings indicate that elemental inclusion in organoids is consistent with human brain tissue and involves P, S, K, Ca, Fe and Zn. Occurrence of different concentration gradients also suggests active regulation of elemental transmembrane transport. Finally, the analysis of pairs of elements shows interesting elemental interaction patterns that change from 30 to 45 days of development, suggesting short- or long-term associations, such as storage in similar compartments or relevance for time-dependent biological processes. These findings shed light on which trace elements are important during human brain development and will support studies aimed to unravel the consequences of disrupted metal homeostasis for neurodevelopmental diseases, including those manifested in adulthood. PMID:28194309

[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.

Increased White Matter Inflammation in Aging- and Alzheimer’s Disease Brain

PubMed Central

Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R.; Olah, Marta; Mantingh-Otter, Ietje J.; Van Dam, Debby; De Deyn, Peter P.; den Dunnen, Wilfred; Eggen, Bart J. L.; Amor, Sandra; Boddeke, Erik

2017-01-01

Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer’s disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [11C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration. PMID:28713239

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

Distribution of a macaque immunosuppressive type D retrovirus in neural, lymphoid, and salivary tissues

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

Lackner, A.A.; Rodriguez, M.H.; Bush, C.E.

1988-06-01

Simian acquired immune deficiency syndrome (SAIDS) in rhesus macaques (Macaca mulatta) at the California Primate Research Center is caused by a type D retrovirus designated SAIDS retrovirus serotype 1 (SRV-1). This syndrome is characterized by profound immunosuppression and death associated with opportunistic infections. Neurologic signs and lesions have not been described as part of this syndrome. The distribution of SRV-1 in the salivary glands, lymph nodes, spleens, thymuses, and brains of eight virus-infected rhesus macaques was examined by immunohistochemistry. Electron microscopy, in situ RNA hybridization, and Southern blot hybridization were also performed on selected tissues to detect viral particles, RNA,more » and DNA, respectively. In seven of eight SRV-1-infected animals, the transmembrane envelope glycoprotein (gp20) of SRV-1 was present in three or more tissues, but never in the brain. In the remaining animal, no viral antigen was detected in any tissue. In this same group of animals, viral nucleic acid was detected in the lymph nodes of six of six animals by Southern blot hybridization, in the salivary glands of two of five animals by both Southern blot and in situ hybridizations, and, surprisingly, in the brains of three of three animals by Southern blot and of three of five animals by in situ hybridization, including the one animal in which viral gp20 was undetectable. None of these animals had neurologic signs or lesions. The detection of viral nucleic acid in the absence of viral antigen in the brain suggests latent SRV-1 infection of the central nervous system.« less

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.

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.

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.

SU-G-IeP1-07: Inaccuracy of Lesion Blood Flow Quantification Related to the Proton Density Reference Image in Arterial Spin Labeling MRI of Brain Tumors

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

Jen, M; Johnson, J; Hou, P

Purpose: Cerebral blood flow quantification in arterial spin labeling (ASL) MRI requires an estimate of the equilibrium magnetization of blood, which is often obtained by a set of proton density (PD) reference image. Normally, a constant blood-brain partition coefficient is assumed across the brain. However, this assumption may not be valid for brain lesions. This study aimed to evaluate the impact of lesion-related PD variations on ASL quantification in patients with brain tumors. Methods: MR images for posttreatment evaluation of 42 patients with brain tumors were retrospectively analyzed. These images were acquired on a 3T MRI scanner, including T2-weighted FLAIR,more » 3D pseudo-continuous ASL and post-contrast T1-weighted images. Anatomical images were coregistered with ASL images using the SPM software. Regions of interest (ROIs) of the enhancing and FLAIR lesions were manually drawn on the coregistered images. ROIs of the contralateral normal appearing tissues were also determined, with the consideration of approximating coil sensitivity patterns in lesion ROIs. Relative lesion blood flow (lesion/contralateral tissue) was calculated from both the CBF map (dependent on the PD) and the ΔM map for comparison. Results: The signal intensities in both enhancing and FLAIR lesions were significantly different than contralateral tissues on the PD reference image (p<0.001). The percent signal difference ranged from −15.9 to 19.2%, with a mean of 5.4% for the enhancing lesion, and from −2.8 to 22.9% with a mean of 10.1% for the FLAIR lesion. The high/low lesion-related PD signal resulted in inversely proportional under-/over-estimation of blood flow in both enhancing and FLAIR lesions. Conclusion: Significant signal differences were found between lesions and contralateral tissues in the PD reference image, which introduced errors in blood flow quantification in ASL. The error can be up to 20% in individual patients with an average of 5- 10% for the group of patients with brain tumors.« less

Measurement and Finite Element Model Validation of Immature Porcine Brain-Skull Displacement during Rapid Sagittal Head Rotations.

PubMed

Pasquesi, Stephanie A; Margulies, Susan S

2018-01-01

Computational models are valuable tools for studying tissue-level mechanisms of traumatic brain injury, but to produce more accurate estimates of tissue deformation, these models must be validated against experimental data. In this study, we present in situ measurements of brain-skull displacement in the neonatal piglet head ( n  = 3) at the sagittal midline during six rapid non-impact rotations (two rotations per specimen) with peak angular velocities averaging 51.7 ± 1.4 rad/s. Marks on the sagittally cut brain and skull/rigid potting surfaces were tracked, and peak values of relative brain-skull displacement were extracted and found to be significantly less than values extracted from a previous axial plane model. In a finite element model of the sagittally transected neonatal porcine head, the brain-skull boundary condition was matched to the measured physical experiment data. Despite smaller sagittal plane displacements at the brain-skull boundary, the corresponding finite element boundary condition optimized for sagittal plane rotations is far less stiff than its axial counterpart, likely due to the prominent role of the boundary geometry in restricting interface movement. Finally, bridging veins were included in the finite element model. Varying the bridging vein mechanical behavior over a previously reported range had no influence on the brain-skull boundary displacements. This direction-specific sagittal plane boundary condition can be employed in finite element models of rapid sagittal head rotations.

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.

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.

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.

Proficiency performance benchmarks for removal of simulated brain tumors using a virtual reality simulator NeuroTouch.

PubMed

AlZhrani, Gmaan; Alotaibi, Fahad; Azarnoush, Hamed; Winkler-Schwartz, Alexander; Sabbagh, Abdulrahman; Bajunaid, Khalid; Lajoie, Susanne P; Del Maestro, Rolando F

2015-01-01

Assessment of neurosurgical technical skills involved in the resection of cerebral tumors in operative environments is complex. Educators emphasize the need to develop and use objective and meaningful assessment tools that are reliable and valid for assessing trainees' progress in acquiring surgical skills. The purpose of this study was to develop proficiency performance benchmarks for a newly proposed set of objective measures (metrics) of neurosurgical technical skills performance during simulated brain tumor resection using a new virtual reality simulator (NeuroTouch). Each participant performed the resection of 18 simulated brain tumors of different complexity using the NeuroTouch platform. Surgical performance was computed using Tier 1 and Tier 2 metrics derived from NeuroTouch simulator data consisting of (1) safety metrics, including (a) volume of surrounding simulated normal brain tissue removed, (b) sum of forces utilized, and (c) maximum force applied during tumor resection; (2) quality of operation metric, which involved the percentage of tumor removed; and (3) efficiency metrics, including (a) instrument total tip path lengths and (b) frequency of pedal activation. All studies were conducted in the Neurosurgical Simulation Research Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada. A total of 33 participants were recruited, including 17 experts (board-certified neurosurgeons) and 16 novices (7 senior and 9 junior neurosurgery residents). The results demonstrated that "expert" neurosurgeons resected less surrounding simulated normal brain tissue and less tumor tissue than residents. These data are consistent with the concept that "experts" focused more on safety of the surgical procedure compared with novices. By analyzing experts' neurosurgical technical skills performance on these different metrics, we were able to establish benchmarks for goal proficiency performance training of neurosurgery residents. This study furthers our understanding of expert neurosurgical performance during the resection of simulated virtual reality tumors and provides neurosurgical trainees with predefined proficiency performance benchmarks designed to maximize the learning of specific surgical technical skills. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

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...

Mapping phosphorylation rate of fluoro-deoxy-glucose in rat brain by 19F chemical shift imaging

PubMed Central

Coman, Daniel; Sanganahalli, Basavaraju G.; Cheng, David; McCarthy, Timothy; Rothman, Douglas L.; Hyder, Fahmeed

2014-01-01

19F magnetic resonance spectroscopy (MRS) studies of 2-fluoro-2-deoxy-D-glucose (FDG) and 2-fluoro-2-deoxy-D-glucose-6-phosphate (FDG-6P) can be used for directly assessing total glucose metabolism in vivo. To date, 19F MRS measurements of FDG phosphorylation in the brain have either been achieved ex vivo from extracted tissue or in vivo by unusually long acquisition times. Electrophysiological and functional magnetic resonance imaging (fMRI) measurements indicate that FDG doses up to 500mg/kg can be tolerated with minimal side effects on cerebral physiology and evoked fMRI-BOLD responses to forepaw stimulation. In halothane-anesthetized rats, we report localized in vivo detection and separation of FDG and FDG-6P MRS signals with 19F 2D chemical shift imaging (CSI) at 11.7T. A metabolic model based on reversible transport between plasma and brain tissue, which included a non-saturable plasma to tissue component, was used to calculate spatial distribution of FDG and FDG-6P concentrations in rat brain. In addition, spatial distribution of rate constants and metabolic fluxes of FDG to FDG-6P conversion were estimated. Mapping the rate of FDG to FDG-6P conversion by 19F CSI provides an MR methodology that could impact other in vivo applications such as characterization of tumor pathophysiology. PMID:24581725

Predicting the Electric Field Distribution in the Brain for the Treatment of Glioblastoma

PubMed Central

Miranda, Pedro C.; Mekonnen, Abeye; Salvador, Ricardo; Basser, Peter J.

2014-01-01

The use of alternating electric fields has been recently proposed for the treatment of recurrent glioblastoma. In order to predict the electric field distribution in the brain during the application of such tumor treating fields (TTF), we constructed a realistic head model from MRI data and placed transducer arrays on the scalp to mimic an FDA-approved medical device. Values for the tissue dielectric properties were taken from the literature; values for the device parameters were obtained from the manufacturer. The finite element method was used to calculate the electric field distribution in the brain. We also included a “virtual lesion” in the model to simulate the presence of an idealized tumor. The calculated electric field in the brain varied mostly between 0.5 and 2.0 V/cm and exceeded 1.0 V/cm in 60% of the total brain volume. Regions of local field enhancement occurred near interfaces between tissues with different conductivities wherever the electric field was perpendicular to those interfaces. These increases were strongest near the ventricles but were also present outside the tumor’s necrotic core and in some parts of the gray matter-white matter interface. The electric field values predicted in this model brain are in reasonably good agreement with those that have been shown to reduce cancer cell proliferation in vitro. The electric field distribution is highly non-uniform and depends on tissue geometry and dielectric properties. This could explain some of the variability in treatment outcomes. The proposed modeling framework could be used to better understand the physical basis of TTF efficacy through retrospective analysis and to improve TTF treatment planning. PMID:25003941

Predicting the electric field distribution in the brain for the treatment of glioblastoma

NASA Astrophysics Data System (ADS)

Miranda, Pedro C.; Mekonnen, Abeye; Salvador, Ricardo; Basser, Peter J.

2014-08-01

The use of alternating electric fields has been recently proposed for the treatment of recurrent glioblastoma. In order to predict the electric field distribution in the brain during the application of such tumor treating fields (TTF), we constructed a realistic head model from MRI data and placed transducer arrays on the scalp to mimic an FDA-approved medical device. Values for the tissue dielectric properties were taken from the literature; values for the device parameters were obtained from the manufacturer. The finite element method was used to calculate the electric field distribution in the brain. We also included a ‘virtual lesion’ in the model to simulate the presence of an idealized tumor. The calculated electric field in the brain varied mostly between 0.5 and 2.0 V cm - 1 and exceeded 1.0 V cm - 1 in 60% of the total brain volume. Regions of local field enhancement occurred near interfaces between tissues with different conductivities wherever the electric field was perpendicular to those interfaces. These increases were strongest near the ventricles but were also present outside the tumor’s necrotic core and in some parts of the gray matter-white matter interface. The electric field values predicted in this model brain are in reasonably good agreement with those that have been shown to reduce cancer cell proliferation in vitro. The electric field distribution is highly non-uniform and depends on tissue geometry and dielectric properties. This could explain some of the variability in treatment outcomes. The proposed modeling framework could be used to better understand the physical basis of TTF efficacy through retrospective analysis and to improve TTF treatment planning.

Predicting the electric field distribution in the brain for the treatment of glioblastoma.

PubMed

Miranda, Pedro C; Mekonnen, Abeye; Salvador, Ricardo; Basser, Peter J

2014-08-07

The use of alternating electric fields has been recently proposed for the treatment of recurrent glioblastoma. In order to predict the electric field distribution in the brain during the application of such tumor treating fields (TTF), we constructed a realistic head model from MRI data and placed transducer arrays on the scalp to mimic an FDA-approved medical device. Values for the tissue dielectric properties were taken from the literature; values for the device parameters were obtained from the manufacturer. The finite element method was used to calculate the electric field distribution in the brain. We also included a 'virtual lesion' in the model to simulate the presence of an idealized tumor. The calculated electric field in the brain varied mostly between 0.5 and 2.0 V cm( - 1) and exceeded 1.0 V cm( - 1) in 60% of the total brain volume. Regions of local field enhancement occurred near interfaces between tissues with different conductivities wherever the electric field was perpendicular to those interfaces. These increases were strongest near the ventricles but were also present outside the tumor's necrotic core and in some parts of the gray matter-white matter interface. The electric field values predicted in this model brain are in reasonably good agreement with those that have been shown to reduce cancer cell proliferation in vitro. The electric field distribution is highly non-uniform and depends on tissue geometry and dielectric properties. This could explain some of the variability in treatment outcomes. The proposed modeling framework could be used to better understand the physical basis of TTF efficacy through retrospective analysis and to improve TTF treatment planning.

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.

A Method for Isolation of Extracellular Vesicles and Characterization of Exosomes from Brain Extracellular Space.

PubMed

Pérez-González, Rocío; Gauthier, Sebastien A; Kumar, Asok; Saito, Mitsuo; Saito, Mariko; Levy, Efrat

2017-01-01

Extracellular vesicles (EV), including exosomes, secreted vesicles of endocytic origin, and microvesicles derived from the plasma membrane, have been widely isolated and characterized from conditioned culture media and bodily fluids. The difficulty in isolating EV from tissues, however, has hindered their study in vivo. Here, we describe a novel method designed to isolate EV and characterize exosomes from the extracellular space of brain tissues. The purification of EV is achieved by gentle dissociation of the tissue to free the brain extracellular space, followed by sequential low-speed centrifugations, filtration, and ultracentrifugations. To further purify EV from other extracellular components, they are separated on a sucrose step gradient. Characterization of the sucrose step gradient fractions by electron microscopy demonstrates that this method yields pure EV preparations free of large vesicles, subcellular organelles, or debris. The level of EV secretion and content are determined by assays for acetylcholinesterase activity and total protein estimation, and exosomal identification and protein content are analyzed by Western blot and immuno-electron microscopy. Additionally, we present here a method to delipidate EV in order to improve the resolution of downstream electrophoretic analysis of EV proteins.

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

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.

Common disease signatures from gene expression analysis in Huntington's disease human blood and brain.

PubMed

Mina, Eleni; van Roon-Mom, Willeke; Hettne, Kristina; van Zwet, Erik; Goeman, Jelle; Neri, Christian; A C 't Hoen, Peter; Mons, Barend; Roos, Marco

2016-08-01

Huntington's disease (HD) is a devastating brain disorder with no effective treatment or cure available. The scarcity of brain tissue makes it hard to study changes in the brain and impossible to perform longitudinal studies. However, peripheral pathology in HD suggests that it is possible to study the disease using peripheral tissue as a monitoring tool for disease progression and/or efficacy of novel therapies. In this study, we investigated if blood can be used to monitor disease severity and progression in brain. Since previous attempts using only gene expression proved unsuccessful, we compared blood and brain Huntington's disease signatures in a functional context. Microarray HD gene expression profiles from three brain regions were compared to the transcriptome of HD blood generated by next generation sequencing. The comparison was performed with a combination of weighted gene co-expression network analysis and literature based functional analysis (Concept Profile Analysis). Uniquely, our comparison of blood and brain datasets was not based on (the very limited) gene overlap but on the similarity between the gene annotations in four different semantic categories: "biological process", "cellular component", "molecular function" and "disease or syndrome". We identified signatures in HD blood reflecting a broad pathophysiological spectrum, including alterations in the immune response, sphingolipid biosynthetic processes, lipid transport, cell signaling, protein modification, spliceosome, RNA splicing, vesicle transport, cell signaling and synaptic transmission. Part of this spectrum was reminiscent of the brain pathology. The HD signatures in caudate nucleus and BA4 exhibited the highest similarity with blood, irrespective of the category of semantic annotations used. BA9 exhibited an intermediate similarity, while cerebellum had the least similarity. We present two signatures that were shared between blood and brain: immune response and spinocerebellar ataxias. Our results demonstrate that HD blood exhibits dysregulation that is similar to brain at a functional level, but not necessarily at the level of individual genes. We report two common signatures that can be used to monitor the pathology in brain of HD patients in a non-invasive manner. Our results are an exemplar of how signals in blood data can be used to represent brain disorders. Our methodology can be used to study disease specific signatures in diseases where heterogeneous tissues are involved in the pathology.

Interfacing with the Brain using Organic Electronics

NASA Astrophysics Data System (ADS)

Malliaras, George

One of the most important scientific and technological frontiers of our time lies in the interface between electronics and the human brain. Interfacing the most advanced human engineering endeavor with nature's most refined creation promises to help elucidate aspects of the brain's working mechanism and deliver new tools for diagnosis and treatment of a host of pathologies including epilepsy and Parkinson's disease. Current solutions, however, are limited by the materials that are brought in contact with the tissue and transduce signals across the biotic/abiotic interface. The field of organic electronics has made available materials with a unique combination of attractive properties, including mechanical flexibility, mixed ionic/electronic conduction, enhanced biocompatibility, and capability for drug delivery. I will present examples of organic-based devices for recording and stimulation of brain activity, highlighting the connection between materials properties and device performance. I will show that organic electronic materials provide unparalleled opportunities to design devices that improve our understanding of brain physiology and pathology, and can be used to deliver new therapies.

[Therapeutic strategies targeting brain tumor stem cells].

PubMed

Toda, Masahiro

2009-07-01

Progress in stem cell research reveals cancer stem cells to be present in a variety of malignant tumors. Since they exhibit resistance to anticancer drugs and radiotherapy, analysis of their properties has been rapidly carried forward as an important target for the treatment of intractable malignancies, including brain tumors. In fact, brain cancer stem cells (BCSCs) have been isolated from brain tumor tissue and brain tumor cell lines by using neural stem cell culture methods and isolation methods for side population (SP) cells, which have high drug-efflux capacity. Although the analysis of the properties of BCSCs is the most important to developing methods in treating BCSCs, the absence of BCSC purification methods should be remedied by taking it up as an important research task in the immediate future. Thus far, there are no effective treatment methods for BCSCs, and several treatment methods have been proposed based on the cell biology characteristics of BCSCs. In this article, I outline potential treatment methods damaging treatment-resistant BCSCs, including immunotherapy which is currently a topic of our research.

Multilayered tissues model for wave propagation loss assessment in cochlear implants

NASA Astrophysics Data System (ADS)

Paun, Maria-Alexandra; Dehollain, Catherine

2017-05-01

In this paper, a study of the power loss attenuation of the plane wave travelling through the tissue layers, from the outside to the inside of the skull within a cochlear implant, is performed. Different implantation depths of the internal antenna from 10 to 30 mm are considered. To this purpose, the gain and attenuation in dB are studied. A multilayer tissue model is developed, consisting of mainly skin, mastoid bone and brain. An s-parameter analysis is also carried out, using loop antennas and simulated head tissue. Ansoft Ansys® HFSS software is used for electro-magnetic simulations of the antennas, placed in different types of human tissues. Smith charts for antenna placed in both skin and multi-tissue model are included.

Relative value of diverse brain MRI and blood-based biomarkers for predicting cognitive decline in the elderly

NASA Astrophysics Data System (ADS)

Madsen, Sarah K.; Ver Steeg, Greg; Daianu, Madelaine; Mezher, Adam; Jahanshad, Neda; Nir, Talia M.; Hua, Xue; Gutman, Boris A.; Galstyan, Aram; Thompson, Paul M.

2016-03-01

Cognitive decline accompanies many debilitating illnesses, including Alzheimer's disease (AD). In old age, brain tissue loss also occurs along with cognitive decline. Although blood tests are easier to perform than brain MRI, few studies compare brain scans to standard blood tests to see which kinds of information best predict future decline. In 504 older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we first used linear regression to assess the relative value of different types of data to predict cognitive decline, including 196 blood panel biomarkers, 249 MRI biomarkers obtained from the FreeSurfer software, demographics, and the AD-risk gene APOE. A subset of MRI biomarkers was the strongest predictor. There was no specific blood marker that increased predictive accuracy on its own, we found that a novel unsupervised learning method, CorEx, captured weak correlations among blood markers, and the resulting clusters offered unique predictive power.

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.

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.

[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.

Application of Targeted Mass Spectrometry for the Quantification of Sirtuins in the Central Nervous System

NASA Astrophysics Data System (ADS)

Jayasena, T.; Poljak, A.; Braidy, N.; Zhong, L.; Rowlands, B.; Muenchhoff, J.; Grant, R.; Smythe, G.; Teo, C.; Raftery, M.; Sachdev, P.

2016-10-01

Sirtuin proteins have a variety of intracellular targets, thereby regulating multiple biological pathways including neurodegeneration. However, relatively little is currently known about the role or expression of the 7 mammalian sirtuins in the central nervous system. Western blotting, PCR and ELISA are the main techniques currently used to measure sirtuin levels. To achieve sufficient sensitivity and selectivity in a multiplex-format, a targeted mass spectrometric assay was developed and validated for the quantification of all seven mammalian sirtuins (SIRT1-7). Quantification of all peptides was by multiple reaction monitoring (MRM) using three mass transitions per protein-specific peptide, two specific peptides for each sirtuin and a stable isotope labelled internal standard. The assay was applied to a variety of samples including cultured brain cells, mammalian brain tissue, CSF and plasma. All sirtuin peptides were detected in the human brain, with SIRT2 being the most abundant. Sirtuins were also detected in human CSF and plasma, and guinea pig and mouse tissues. In conclusion, we have successfully applied MRM mass spectrometry for the detection and quantification of sirtuin proteins in the central nervous system, paving the way for more quantitative and functional studies.

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.

Effect of supplemental taurine on juvenile channel catfish Ictalurus punctatus growth

USDA-ARS?s Scientific Manuscript database

Taurine is a beta-amino sulfur amino acid found in most animal tissues. It has many important biological functions in mammals including membrane stabilization, antioxidation, cellular osmoregulation, detoxification, neuromodulation, and brain and eye development. Taurine supplementation in juvenil...

Neurotoxicity induced by arsenic in Gallus Gallus: Regulation of oxidative stress and heat shock protein response.

PubMed

Zhao, Panpan; Guo, Ying; Zhang, Wen; Chai, Hongliang; Xing, Houjuan; Xing, Mingwei

2017-01-01

Arsenic, a naturally occurring heavy metal pollutant, is one of the functioning risk factors for neurological toxicity in humans. However, little is known about the effects of arsenic on the nervous system of Gallus Gallus. To investigate whether arsenic induce neurotoxicity and influence the oxidative stress and heat shock proteins (Hsps) response in chickens, seventy-two 1-day-old male Hy-line chickens were treated with different doses of arsenic trioxide (As 2 O 3 ). The histological changes, antioxidant enzyme activity, and the expressions of Hsps were detected. Results showed slightly histology changes were obvious in the brain tissues exposure to arsenic. The activities of Glutathione peroxidase (GSH-Px) and catalase (CAT) were decreased compared to the control, whereas the malondialdehyde (MDA) content was increased gradually along with increase in diet-arsenic. The mRNA levels of Hsps and protein expressions of Hsp60 and Hsp70 were up-regulated. These results suggested that sub-chronic exposure to arsenic induced neurotoxicity in chickens. Arsenic exposure disturbed the balance of oxidants and antioxidants. Increased heat shock response tried to protect chicken brain tissues from tissues damage caused by oxidative stress. The mechanisms of neurotoxicity induced by arsenic include oxidative stress and heat shock protein response in chicken brain tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Immunohistochemical Demonstration of Specific Antigens in the Human Brain Fixed in Zinc-ethanol-Formaldehyde

PubMed Central

Korzhevskii, D.E.; Sukhorukova, E.G.; Kirik, O.V.; Grigorev, I.P.

2015-01-01

Tissue fixation is critical for immunohistochemistry. Recently, we developed a zinc-ethanol-formalin fixative (ZEF), and the present study was aimed to assess the applicability of the ZEF for the human brain histology and immunohistochemistry and to evaluate the detectability of different antigens in the human brain fixed with ZEF. In total, 11 antigens were tested, including NeuN, neuron-specific enolase, GFAP, Iba-1, calbindin, calretinin, choline acetyltransferase, glutamic acid decarboxylase (GAD65), tyrosine hydroxylase, synaptophysin, and α-tubulin. The obtained data show that: i) the ZEF has potential for use in general histological practice, where detailed characterization of human brain morphology is needed; ii) the antigens tested are well-preserved in the human brain specimens fixed in the ZEF. PMID:26428887

Salmonella as a biological "Trojan horse" for neoplasia: future possibilities including brain cancer.

PubMed

Mlynarczyk, Gregory S A; Berg, Carrie A; Withrock, Isabelle C; Fick, Meghan E; Anderson, Stephen J; Laboissonniere, Lauren A; Jefferson, Matthew A; Brewer, Matthew T; Stock, Matthew L; Lange, Jennifer K; Luna, K C; Acharya, Sreemoyee; Kanuri, Sriharsha; Sharma, Shaunik; Kondru, Naveen C; McCormack, Garrett R; Carlson, Steve A

2014-09-01

This manuscript considers available evidence that a specific Salmonella strain could be used as an effective orally-administered option for cancer therapy involving the brain. It has been established that Salmonella preferentially colonizes neoplastic tissue and thrives as a facultative anaerobe in the intra-tumor environment. Although Salmonella accumulates in tumors by passive processes, it is still possible for lipopolysaccharide to cause sepsis and endotoxic shock during the migration of bacteria to the tumor site. An LPS-free version of a recently identified Salmonella isolate may have the capability to circumvent the blood brain barrier and provide a safer method of reaching brain tumors. This isolate merits further research as a "Trojan horse" for future oral biotherapy of brain cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

3-D Bioprinting of Neural Tissue for Applications in Cell Therapy and Drug Screening

PubMed Central

Thomas, Michaela; Willerth, Stephanie M.

2017-01-01

Neurodegenerative diseases affect millions of individuals in North America and cost the health-care industry billions of dollars for treatment. Current treatment options for degenerative diseases focus on physical rehabilitation or drug therapies, which temporarily mask the effects of cell damage, but quickly lose their efficacy. Cell therapies for the central nervous system remain an untapped market due to the complexity involved in growing neural tissues, controlling their differentiation, and protecting them from the hostile environment they meet upon implantation. Designing tissue constructs for the discovery of better drug treatments are also limited due to the resolution needed for an accurate cellular representation of the brain, in addition to being expensive and difficult to translate to biocompatible materials. 3-D printing offers a streamlined solution for engineering brain tissue for drug discovery or, in the future, for implantation. New microfluidic and bioplotting devices offer increased resolution, little impact on cell viability and have been tested with several bioink materials including fibrin, collagen, hyaluronic acid, poly(caprolactone), and poly(ethylene glycol). This review details current efforts at bioprinting neural tissue and highlights promising avenues for future work. PMID:29204424

Tomographic reconstruction of layered tissue structures

NASA Astrophysics Data System (ADS)

Hielscher, Andreas H.; Azeez-Jan, Mohideen; Bartel, Sebastian

2001-11-01

In recent years the interest in the determination of optical properties of layered tissue structure has resurfaced. Applications include, for example, studies on layered skin tissue and underlying muscles, imaging of the brain underneath layers of skin, skull, and meninges, and imaging of the fetal head in utero beneath the layered structures of the maternal abdomen. In this work we approach the problem of layered structures in the framework of model-based iterative image reconstruction schemes. These schemes are currently developed to determine the optical properties inside tissue from measurement on the surface. If applied to layered structure these techniques yield substantial improvements over currently available semi-analytical approaches.

Locomotor activity and tissue levels following acute ...

EPA Pesticide Factsheets

Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metrics. Products of cyhalothrin, a type II pyrethroid, include mixtures of isomers (e.g., λ-cyhalothrin) as well as enriched active isomers (e.g., γ-cyhalothrin). We measured acute changes in locomotor activity in adult male rats and directly correlated these changes to peak brain and plasma concentrations of λ- and γ-cyhalothrin using a within-subject design. One-hour locomotor activity studies were conducted 1.5 h after oral gavage dosing, and immediately thereafter plasma and brains were collected for analyzing tissue levels using LC/MS/MS methods. Both isomers produced dose-related decreases in activity counts, and the effective dose range for γ-cyhalothrin was lower than for λ-cyhalothrin. Doses calculated to decrease activity by 50% were 2-fold lower for the γ-isomer (1.29 mg/kg) compared to λ-cyhalothrin (2.65 mg/kg). Salivation, typical of type II pyrethroids, was also observed at lower doses of γ-cyhalothrin. Administered dose correlated well with brain and plasma concentrations, which furthermore showed good correlations with activity changes. Brain and plasma levels were tightly correlated across doses. While γ-cyhalothrin was 2-fold more potent based on administ

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.

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.

Investigation of the usefulness of fluorescein sodium fluorescence in stereotactic brain biopsy.

PubMed

Thien, Ady; Han, Julian Xinguang; Kumar, Krishan; Ng, Yew Poh; Rao, Jai Prashanth; Ng, Wai Hoe; King, Nicolas Kon Kam

2018-02-01

Intraoperative frozen section assessment, to confirm acquisition of pathological tissues, is used in stereotactic brain biopsy to minimise sampling errors. Limitations include the dependence on dedicated neuro-oncology pathologists and an increase in operative duration. We investigated the use of intraoperative fluorescein sodium, and compared it to frozen section assessment, for confirming pathological tissue samples in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions. This prospective observational study consisted of 18 consecutive patients (12 men; median age, 63 years) who underwent stereotactic biopsy of gadolinium-contrast-enhancing brain lesions with intravenous fluorescein sodium administration. Twenty-three specimens were obtained and examined for the presence of fluorescence using a microscope with fluorescence visualisation capability. Positive and negative predictive values were calculated based on the fluorescence status of the biopsy samples with its corresponding intraoperative frozen section and definitive histopathological diagnosis. Nineteen specimens (83%) were fluorescent and four (17%) were non-fluorescent. All 19 fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment and were suitable for histopathological diagnosis. Three of the non-fluorescent specimens were confirmed to be lesional on intraoperative frozen section assessment. One non-fluorescent specimen was non-diagnostic on frozen section and histological assessments. The positive predictive value was 100% and the negative predictive value was 25%. Fluorescein sodium fluorescence is as accurate as frozen section assessment in confirming sampling of pathological tissue in the stereotactic biopsy of gadolinium-contrast-enhancing brain lesions. Fluorescein sodium fluorescence-guided stereotactic biopsy is a useful addition to the neurosurgical armamentarium.

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

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.

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...

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.

Polyploidization of glia in neural development links tissue growth to blood-brain barrier integrity.

PubMed

Unhavaithaya, Yingdee; Orr-Weaver, Terry L

2012-01-01

Proper development requires coordination in growth of the cell types composing an organ. Many plant and animal cells are polyploid, but how these polyploid tissues contribute to organ growth is not well understood. We found the Drosophila melanogaster subperineurial glia (SPG) to be polyploid, and ploidy is coordinated with brain mass. Inhibition of SPG polyploidy caused rupture of the septate junctions necessary for the blood-brain barrier. Thus, the increased SPG cell size resulting from polyploidization is required to maintain the SPG envelope surrounding the growing brain. Polyploidization likely is a conserved strategy to coordinate tissue growth during organogenesis, with potential vertebrate examples.

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.

Caffeine and Cannabis Effects on Vital Neurotransmitters and Enzymes in the Brain Tissue of Juvenile Experimental Rats

PubMed Central

Owolabi, J.O.; Olatunji, S.Y.; Olanrewaju, A.J.

2017-01-01

Background Caffeine and cannabis are globally consumed and abused psychoactive substances. While caffeine is legally used in various forms, including in tea and coffee as beverages, it is also consumed in soda and energy drinks as additives. Cannabis, on the other hand, is considered illegal in most countries; albeit, it is being consumed globally particularly by adolescents. Purpose The adolescent stage marks a critical stage of brain development and maturation. Influences of agents on the brain at this stage may affect neuronal structural and functional attributes. To this end, the current experiment considered the effects of cannabis and caffeine on selected key neurotransmitters and enzymes in the brain tissues after regimented caffeine and cannabis treatment for 21 days. Methods A total of 72 juvenile Wistar rats that were approximately 40 days old were divided into 6 groups A-F. The group A served as the control. Other groups were administered various dosages of caffeine or cannabis in distilled water, using oral gavages as follows: group B animals received 100 mg/kg body weight of caffeine, group C animals received 50 mg/kg body weight of caffeine, group D animals received 500 mg/kg body weight of cannabis, group E animals received 200 mg/kg body weight of cannabis, and group F received a low dose of cannabis (200 mg/kg body weight) plus a low dose of caffeine (50 mg/kg body weight). The animals were killed by cervical dislocation 24 h after the last administration. The brain tissues were excised and homogenized. The enzymes cytochrome C oxidase and glucose-6-phosphate dehydrogenase were assayed to observe tissue energy metabolism while the neurotransmitters gamma-amino butyric acid (GABA), glutamate, and dopamine were assayed to observe the effects of the psychoactive substances on their activities relative to mental activities. Results GABA, glutamate, and dopamine were generally higher in the treated groups of animals. The levels of G-6-PDH were higher in all treated animals’ brains. Caffeine produced quite more significant effects relative to cannabis and the combination of both increased the level of G-6-PDH significantly. Conclusion Results showed that caffeine and cannabis influenced the activities of the enzymes and neurotransmitters in the brain. Both stimulants altered brain chemistry relative to the tested enzymes and neurotransmitters. PMID:28588361

Caffeine and Cannabis Effects on Vital Neurotransmitters and Enzymes in the Brain Tissue of Juvenile Experimental Rats.

PubMed

Owolabi, J O; Olatunji, S Y; Olanrewaju, A J

2017-05-01

Caffeine and cannabis are globally consumed and abused psychoactive substances. While caffeine is legally used in various forms, including in tea and coffee as beverages, it is also consumed in soda and energy drinks as additives. Cannabis, on the other hand, is considered illegal in most countries; albeit, it is being consumed globally particularly by adolescents. The adolescent stage marks a critical stage of brain development and maturation. Influences of agents on the brain at this stage may affect neuronal structural and functional attributes. To this end, the current experiment considered the effects of cannabis and caffeine on selected key neurotransmitters and enzymes in the brain tissues after regimented caffeine and cannabis treatment for 21 days. A total of 72 juvenile Wistar rats that were approximately 40 days old were divided into 6 groups A-F. The group A served as the control. Other groups were administered various dosages of caffeine or cannabis in distilled water, using oral gavages as follows: group B animals received 100 mg/kg body weight of caffeine, group C animals received 50 mg/kg body weight of caffeine, group D animals received 500 mg/kg body weight of cannabis, group E animals received 200 mg/kg body weight of cannabis, and group F received a low dose of cannabis (200 mg/kg body weight) plus a low dose of caffeine (50 mg/kg body weight). The animals were killed by cervical dislocation 24 h after the last administration. The brain tissues were excised and homogenized. The enzymes cytochrome C oxidase and glucose-6-phosphate dehydrogenase were assayed to observe tissue energy metabolism while the neurotransmitters gamma-amino butyric acid (GABA), glutamate, and dopamine were assayed to observe the effects of the psychoactive substances on their activities relative to mental activities. GABA, glutamate, and dopamine were generally higher in the treated groups of animals. The levels of G-6-PDH were higher in all treated animals' brains. Caffeine produced quite more significant effects relative to cannabis and the combination of both increased the level of G-6-PDH significantly. Results showed that caffeine and cannabis influenced the activities of the enzymes and neurotransmitters in the brain. Both stimulants altered brain chemistry relative to the tested enzymes and neurotransmitters.

Genotyping and pathobiologic characterization of canine parvovirus circulating in Nanjing, China

PubMed Central

2013-01-01

Background Canine parvovirus (CPV) is an important pathogen that causes acute enteric disease in dogs. It has mutated and spread throughout the world in dog populations. We provide an update on the molecular characterization of CPV that circulated in Nanjing, a provincial capital in China between 2009 and 2012. Results Seventy rectal swab samples were collected from the dogs diagnosed with CPV infection in 8 animal hospitals of Nanjing. Sequence analysis of VP2 genes of 31 samples revealed that 29 viral strains belonged to CPV-2a subtype, while other two strains were classified into CPV-2b. To investigate the pathogenicity of the prevalent virus, we isolated CPV-2a and performed the animal experiment. Nine beagles were inoculated with 105.86 of 50% tissue culture infectious doses (TCID50) of the virus. All the experimentally infected beagles exhibited mild to moderate mucoid or watery diarrhea on day 4 post-infection (p.i.). On day 9 p.i., characteristic histopathological lesions were clearly observed in multiple organs of infected dogs, including liver, spleen, kidney, brain and all segments of the small and large intestines, while viral DNA and antigen staining could be detected in the sampled tissues. It is notable that canine parvovirus was isolated in one from two brain samples processed. Conclusion Our results indicated that CPV-2a is the predominant subtype in Nanjing of China. And this virus caused extensive lesions in a variety of tissues, including the brain. PMID:23988202

Genotyping and pathobiologic characterization of canine parvovirus circulating in Nanjing, China.

PubMed

Zhao, Yanbing; Lin, Yan; Zeng, Xujian; Lu, Chengping; Hou, Jiafa

2013-08-29

Canine parvovirus (CPV) is an important pathogen that causes acute enteric disease in dogs. It has mutated and spread throughout the world in dog populations. We provide an update on the molecular characterization of CPV that circulated in Nanjing, a provincial capital in China between 2009 and 2012. Seventy rectal swab samples were collected from the dogs diagnosed with CPV infection in 8 animal hospitals of Nanjing. Sequence analysis of VP2 genes of 31 samples revealed that 29 viral strains belonged to CPV-2a subtype, while other two strains were classified into CPV-2b. To investigate the pathogenicity of the prevalent virus, we isolated CPV-2a and performed the animal experiment. Nine beagles were inoculated with 105.86 of 50% tissue culture infectious doses (TCID50) of the virus. All the experimentally infected beagles exhibited mild to moderate mucoid or watery diarrhea on day 4 post-infection (p.i.). On day 9 p.i., characteristic histopathological lesions were clearly observed in multiple organs of infected dogs, including liver, spleen, kidney, brain and all segments of the small and large intestines, while viral DNA and antigen staining could be detected in the sampled tissues. It is notable that canine parvovirus was isolated in one from two brain samples processed. Our results indicated that CPV-2a is the predominant subtype in Nanjing of China. And this virus caused extensive lesions in a variety of tissues, including the brain.

Sterile Inflammation of Brain, due to Activation of Innate Immunity, as a Culprit in Psychiatric Disorders

PubMed Central

Ratajczak, Mariusz Z.; Pedziwiatr, Daniel; Cymer, Monika; Kucia, Magda; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy

2018-01-01

Evidence has accumulated that the occurrence of psychiatric disorders is related to chronic inflammation. In support of this linkage, changes in the levels of circulating pro-inflammatory cytokines and chemokines in the peripheral blood (PB) of psychiatric patients as well as correlations between chronic inflammatory processes and psychiatric disorders have been described. Furthermore, an inflammatory process known as “sterile inflammation” when initiated directly in brain tissue may trigger the onset of psychoses. In this review, we will present the hypothesis that prolonged or chronic activation of the complement cascade (ComC) directly triggers inflammation in the brain and affects the proper function of this organ. Based on the current literature and our own work on mechanisms activating the ComC we hypothesize that inflammation in the brain is initiated by the mannan-binding lectin pathway of ComC activation. This activation is triggered by an increase in brain tissue of danger-associated molecular pattern (DAMP) mediators, including extracellular ATP and high-mobility group box 1 (HMGB1) protein, which are recognized by circulating pattern-recognition receptors, including mannan-binding lectin (MBL), that activate the ComC. On the other hand, this process is controlled by the anti-inflammatory action of heme oxygenase 1 (HO-1). In this review, we will try to connect changes in the release of DAMPs in the brain with inflammatory processes triggered by the innate immunity involving activation of the ComC as well as the inflammation-limiting effects of the anti-inflammatory HO-1 pathway. We will also discuss parallel observations that during ComC activation subsets of stem cells are mobilized into PB from bone marrow that are potentially involved in repair mechanisms. PMID:29541038

Sterile Inflammation of Brain, due to Activation of Innate Immunity, as a Culprit in Psychiatric Disorders.

PubMed

Ratajczak, Mariusz Z; Pedziwiatr, Daniel; Cymer, Monika; Kucia, Magda; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy

2018-01-01

Evidence has accumulated that the occurrence of psychiatric disorders is related to chronic inflammation. In support of this linkage, changes in the levels of circulating pro-inflammatory cytokines and chemokines in the peripheral blood (PB) of psychiatric patients as well as correlations between chronic inflammatory processes and psychiatric disorders have been described. Furthermore, an inflammatory process known as "sterile inflammation" when initiated directly in brain tissue may trigger the onset of psychoses. In this review, we will present the hypothesis that prolonged or chronic activation of the complement cascade (ComC) directly triggers inflammation in the brain and affects the proper function of this organ. Based on the current literature and our own work on mechanisms activating the ComC we hypothesize that inflammation in the brain is initiated by the mannan-binding lectin pathway of ComC activation. This activation is triggered by an increase in brain tissue of danger-associated molecular pattern (DAMP) mediators, including extracellular ATP and high-mobility group box 1 (HMGB1) protein, which are recognized by circulating pattern-recognition receptors, including mannan-binding lectin (MBL), that activate the ComC. On the other hand, this process is controlled by the anti-inflammatory action of heme oxygenase 1 (HO-1). In this review, we will try to connect changes in the release of DAMPs in the brain with inflammatory processes triggered by the innate immunity involving activation of the ComC as well as the inflammation-limiting effects of the anti-inflammatory HO-1 pathway. We will also discuss parallel observations that during ComC activation subsets of stem cells are mobilized into PB from bone marrow that are potentially involved in repair mechanisms.

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.

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.

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.

Improved spatial coverage for brain 3D PRESS MRSI by automatic placement of outer-volume suppression saturation bands.

PubMed

Ozhinsky, Eugene; Vigneron, Daniel B; Nelson, Sarah J

2011-04-01

To develop a technique for optimizing coverage of brain 3D (1) H magnetic resonance spectroscopic imaging (MRSI) by automatic placement of outer-volume suppression (OVS) saturation bands (sat bands) and to compare the performance for point-resolved spectroscopic sequence (PRESS) MRSI protocols with manual and automatic placement of sat bands. The automated OVS procedure includes the acquisition of anatomic images from the head, obtaining brain and lipid tissue maps, calculating optimal sat band placement, and then using those optimized parameters during the MRSI acquisition. The data were analyzed to quantify brain coverage volume and data quality. 3D PRESS MRSI data were acquired from three healthy volunteers and 29 patients using protocols that included either manual or automatic sat band placement. On average, the automatic sat band placement allowed the acquisition of PRESS MRSI data from 2.7 times larger brain volumes than the conventional method while maintaining data quality. The technique developed helps solve two of the most significant problems with brain PRESS MRSI acquisitions: limited brain coverage and difficulty in prescription. This new method will facilitate routine clinical brain 3D MRSI exams and will be important for performing serial evaluation of response to therapy in patients with brain tumors and other neurological diseases. Copyright © 2011 Wiley-Liss, Inc.

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 ...

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.

Monkey alcohol tissue research resource: banking tissues for alcohol research.

PubMed

Daunais, James B; Davenport, April T; Helms, Christa M; Gonzales, Steven W; Hemby, Scott E; Friedman, David P; Farro, Jonathan P; Baker, Erich J; Grant, Kathleen A

2014-07-01

An estimated 18 million adults in the United States meet the clinical criteria for diagnosis of alcohol abuse or alcoholism, a disorder ranked as the third leading cause of preventable death. In addition to brain pathology, heavy alcohol consumption is comorbid with damage to major organs including heart, lungs, liver, pancreas, and kidneys. Much of what is known about risk for and consequences of heavy consumption derive from rodent or retrospective human studies. The neurobiological effects of chronic intake in rodent studies may not easily translate to humans due to key differences in brain structure and organization between species, including a lack of higher-order cognitive functions, and differences in underlying prefrontal cortical neural structures that characterize the primate brain. Further, rodents do not voluntarily consume large quantities of ethanol (EtOH) and they metabolize it more rapidly than primates. The basis of the Monkey Alcohol Tissue Research Resource (MATRR) is that nonhuman primates, specifically monkeys, show a range of drinking excessive amounts of alcohol (>3.0 g/kg or a 12 drink equivalent per day) over long periods of time (12 to 30 months) with concomitant pathological changes in endocrine, hepatic, and central nervous system (CNS) processes. The patterns and range of alcohol intake that monkeys voluntarily consume parallel what is observed in humans with alcohol use disorders and the longitudinal experimental design spans stages of drinking from the EtOH-naïve state to early exposure through chronic abuse. Age- and sex-matched control animals self-administer an isocaloric solution under identical operant procedures. The MATRR is a unique postmortem tissue bank that provides CNS and peripheral tissues, and associated bioinformatics from monkeys that self-administer EtOH using a standardized experimental paradigm to the broader alcohol research community. This resource provides a translational platform from which we can better understand the disease processes associated with alcoholism. Copyright © 2014 by the Research Society on Alcoholism.

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.

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.

Design and optimization of an ultra wideband and compact microwave antenna for radiometric monitoring of brain temperature.

PubMed

Rodrigues, Dario B; Maccarini, Paolo F; Salahi, Sara; Oliveira, Tiago R; Pereira, Pedro J S; Limao-Vieira, Paulo; Snow, Brent W; Reudink, Doug; Stauffer, Paul R

2014-07-01

We present the modeling efforts on antenna design and frequency selection to monitor brain temperature during prolonged surgery using noninvasive microwave radiometry. A tapered log-spiral antenna design is chosen for its wideband characteristics that allow higher power collection from deep brain. Parametric analysis with the software HFSS is used to optimize antenna performance for deep brain temperature sensing. Radiometric antenna efficiency (η) is evaluated in terms of the ratio of power collected from brain to total power received by the antenna. Anatomical information extracted from several adult computed tomography scans is used to establish design parameters for constructing an accurate layered 3-D tissue phantom. This head phantom includes separate brain and scalp regions, with tissue equivalent liquids circulating at independent temperatures on either side of an intact skull. The optimized frequency band is 1.1-1.6 GHz producing an average antenna efficiency of 50.3% from a two turn log-spiral antenna. The entire sensor package is contained in a lightweight and low-profile 2.8 cm diameter by 1.5 cm high assembly that can be held in place over the skin with an electromagnetic interference shielding adhesive patch. The calculated radiometric equivalent brain temperature tracks within 0.4 °C of the measured brain phantom temperature when the brain phantom is lowered 10 °C and then returned to the original temperature (37 °C) over a 4.6-h experiment. The numerical and experimental results demonstrate that the optimized 2.5-cm log-spiral antenna is well suited for the noninvasive radiometric sensing of deep brain temperature.

Emerging insights into barriers to effective brain tumor therapeutics.

PubMed

Woodworth, Graeme F; Dunn, Gavin P; Nance, Elizabeth A; Hanes, Justin; Brem, Henry

2014-01-01

There is great promise that ongoing advances in the delivery of therapeutics to the central nervous system (CNS) combined with rapidly expanding knowledge of brain tumor patho-biology will provide new, more effective therapies. Brain tumors that form from brain cells, as opposed to those that come from other parts of the body, rarely metastasize outside of the CNS. Instead, the tumor cells invade deep into the brain itself, causing disruption in brain circuits, blood vessel and blood flow changes, and tissue swelling. Patients with the most common and deadly form, glioblastoma (GBM) rarely live more than 2 years even with the most aggressive treatments and often with devastating neurological consequences. Current treatments include maximal safe surgical removal or biopsy followed by radiation and chemotherapy to address the residual tumor mass and invading tumor cells. However, delivering effective and sustained treatments to these invading cells without damaging healthy brain tissue is a major challenge and focus of the emerging fields of nanomedicine and viral and cell-based therapies. New treatment strategies, particularly those directed against the invasive component of this devastating CNS disease, are sorely needed. In this review, we (1) discuss the history and evolution of treatments for GBM, (2) define and explore three critical barriers to improving therapeutic delivery to invasive brain tumors, specifically, the neuro-vascular unit as it relates to the blood brain barrier, the extra-cellular space in regard to the brain penetration barrier, and the tumor genetic heterogeneity and instability in association with the treatment efficacy barrier, and (3) identify promising new therapeutic delivery approaches that have the potential to address these barriers and create sustained, meaningful efficacy against GBM.

Insulin receptor in the brain: Mechanisms of activation and the role in the CNS pathology and treatment.

PubMed

Pomytkin, Igor; Costa-Nunes, João P; Kasatkin, Vladimir; Veniaminova, Ekaterina; Demchenko, Anna; Lyundup, Alexey; Lesch, Klaus-Peter; Ponomarev, Eugene D; Strekalova, Tatyana

2018-04-24

While the insulin receptor (IR) was found in the CNS decades ago, the brain was long considered to be an insulin-insensitive organ. This view is currently revisited, given emerging evidence of critical roles of IR-mediated signaling in development, neuroprotection, metabolism, and plasticity in the brain. These diverse cellular and physiological IR activities are distinct from metabolic IR functions in peripheral tissues, thus highlighting region specificity of IR properties. This particularly concerns the fact that two IR isoforms, A and B, are predominantly expressed in either the brain or peripheral tissues, respectively, and neurons express exclusively IR-A. Intriguingly, in comparison with IR-B, IR-A displays high binding affinity and is also activated by low concentrations of insulin-like growth factor-2 (IGF-2), a regulator of neuronal plasticity, whose dysregulation is associated with neuropathologic processes. Deficiencies in IR activation, insulin availability, and downstream IR-related mechanisms may result in aberrant IR-mediated functions and, subsequently, a broad range of brain disorders, including neurodevelopmental syndromes, neoplasms, neurodegenerative conditions, and depression. Here, we discuss findings on the brain-specific features of IR-mediated signaling with focus on mechanisms of primary receptor activation and their roles in the neuropathology. We aimed to uncover the remaining gaps in current knowledge on IR physiology and highlight new therapies targeting IR, such as IR sensitizers. © 2018 John Wiley & Sons Ltd.

Label-free volumetric optical imaging of intact murine brains

NASA Astrophysics Data System (ADS)

Ren, Jian; Choi, Heejin; Chung, Kwanghun; Bouma, Brett E.

2017-04-01

A central effort of today’s neuroscience is to study the brain’s ’wiring diagram’. The nervous system is believed to be a network of neurons interacting with each other through synaptic connection between axons and dendrites, therefore the neuronal connectivity map not only depicts the underlying anatomy, but also has important behavioral implications. Different approaches have been utilized to decipher neuronal circuits, including electron microscopy (EM) and light microscopy (LM). However, these approaches typically demand extensive sectioning and reconstruction for a brain sample. Recently, tissue clearing methods have enabled the investigation of a fully assembled biological system with greatly improved light penetration. Yet, most of these implementations, still require either genetic or exogenous contrast labeling for light microscopy. Here we demonstrate a high-speed approach, termed as Clearing Assisted Scattering Tomography (CAST), where intact brains can be imaged at optical resolution without labeling by leveraging tissue clearing and the scattering contrast of optical frequency domain imaging (OFDI).

Detection and characterization of naturally acquired West Nile virus infection in a female wild turkey.

PubMed

Zhang, Z; Wilson, F; Read, R; Pace, L; Zhang, S

2006-03-01

An adult female wild turkey exhibiting disorientation and failure to flee when approached was submitted to the Mississippi Veterinary Research and Diagnostic Laboratory. Gross pathologic examination revealed evidence of dehydration and the presence of modest numbers of adult nematodes in the small intestine. Histologic examination revealed extensive multifocal perivascular lymphocytic infiltration in brain, marked heterophilic hyperplasia in bone marrow, and multifocal interstitial lymphocytic infiltration in heart, pancreas, ventriculus, and skeletal muscles. West Nile virus (WNV) was isolated from the brain, lung, and kidney tissues using cultured Vero cells. Higher copies of viral RNA were detected from brain, lung, and kidney than from heart, liver, or spleen by quantitative real-time reverse transcription-polymerase chain reaction (RRT-PCR) analysis. Immunohistochemical (IHC) analysis detected WNV antigen in various tissues including neurons, kidney, respiratory tract epithelium, heart, and bone marrow. On the basis of the data from this investigation, it is concluded that WNV caused encephalitis along with many other pathologic changes in the affected wild turkey.

Comprehensive analysis of a microRNA expression profile in pediatric medulloblastoma.

PubMed

Dai, Junqiang; Li, Qiao; Bing, Zhitong; Zhang, Yinian; Niu, Liang; Yin, Hang; Yuan, Guoqiang; Pan, Yawen

2017-06-01

Medulloblastoma is the most common malignant brain tumor of the central nervous system among children. Medulloblastoma is an embryonal tumor, of which little is known about the pathogenesis. Several efforts have been made to understand the molecular aspects of its tumorigenic pathways; however, these are poorly understood. microRNA (miRNA), a type of non‑coding short RNA, has been proven to be associated with a number of physiological processes and pathological processes of serious diseases, including brain tumors. Differentially expressed miRNAs serve an important role in numerous types of malignancy. The present study aims to define a differentially expressed set of miRNAs in medulloblastoma tumor tissue, compared with normal samples, to improve the understanding of the tumorigenesis. It was identified that 22 miRNAs were upregulated and 26 miRNAs were downregulated in the tumor tissue compared with the normal group. However, when the medulloblastoma tissue was compared with normal cerebellum tissue, 9 miRNAs were identified to be up or downregulated in the tumor samples. The differentially expressed miRNAs in the tumor tissue were identified in order to clarify the networks and pathways of tumorigenesis using Ingenuity Pathway Analysis. Subsequently, key regulatory genes associated with the development of medulloblastoma were identified, including tumor protein p53, insulin like growth factor 1 receptor, argonaute 2, mitogen‑activated protein kinases 1 and 3, sirtuin 1 and Y box binding protein 1.

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.

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

Neuronal nuclei isolation from human postmortem brain tissue.

PubMed

Matevossian, Anouch; Akbarian, Schahram

2008-10-01

Neurons in the human brain become postmitotic largely during prenatal development, and thus maintain their nuclei throughout the full lifespan. However, little is known about changes in neuronal chromatin and nuclear organization during the course of development and aging, or in chronic neuropsychiatric disease. However, to date most chromatin and DNA based assays (other than FISH) lack single cell resolution. To this end, the considerable cellular heterogeneity of brain tissue poses a significant limitation, because typically various subpopulations of neurons are intermingled with different types of glia and other non-neuronal cells. One possible solution would be to grow cell-type specific cultures, but most CNS cells, including neurons, are ex vivo sustainable, at best, for only a few weeks and thus would provide an incomplete model for epigenetic mechanisms potentially operating across the full lifespan. Here, we provide a protocol to extract and purify nuclei from frozen (never fixed) human postmortem brain. The method involves extraction of nuclei in hypotonic lysis buffer, followed by ultracentrifugation and immunotagging with anti-NeuN antibody. Labeled neuronal nuclei are then collected separately using fluorescence-activated sorting. This method should be applicable to any brain region in a wide range of species and suitable for chromatin immunoprecipitation studies with site- and modification-specific anti-histone antibodies, and for DNA methylation and other assays.

Visualizing spatial distribution of alectinib in murine brain using quantitative mass spectrometry imaging.

PubMed

Aikawa, Hiroaki; Hayashi, Mitsuhiro; Ryu, Shoraku; Yamashita, Makiko; Ohtsuka, Naoto; Nishidate, Masanobu; Fujiwara, Yasuhiro; Hamada, Akinobu

2016-03-30

In the development of anticancer drugs, drug concentration measurements in the target tissue have been thought to be crucial for predicting drug efficacy and safety. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is commonly used for determination of average drug concentrations; however, complete loss of spatial information in the target tissue occurs. Mass spectrometry imaging (MSI) has been recently applied as an innovative tool for detection of molecular distribution of pharmacological agents in heterogeneous targets. This study examined the intra-brain transitivity of alectinib, a novel anaplastic lymphoma kinase inhibitor, using a combination of matrix-assisted laser desorption ionization-MSI and LC-MS/MS techniques. We first analyzed the pharmacokinetic profiles in FVB mice and then examined the effect of the multidrug resistance protein-1 (MDR1) using Mdr1a/b knockout mice including quantitative distribution of alectinib in the brain. While no differences were observed between the mice for the plasma alectinib concentrations, diffuse alectinib distributions were found in the brain of the Mdr1a/b knockout versus FVB mice. These results indicate the potential for using quantitative MSI for clarifying drug distribution in the brain on a microscopic level, in addition to suggesting a possible use in designing studies for anticancer drug development and translational research.

Visualizing spatial distribution of alectinib in murine brain using quantitative mass spectrometry imaging

PubMed Central

Aikawa, Hiroaki; Hayashi, Mitsuhiro; Ryu, Shoraku; Yamashita, Makiko; Ohtsuka, Naoto; Nishidate, Masanobu; Fujiwara, Yasuhiro; Hamada, Akinobu

2016-01-01

In the development of anticancer drugs, drug concentration measurements in the target tissue have been thought to be crucial for predicting drug efficacy and safety. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is commonly used for determination of average drug concentrations; however, complete loss of spatial information in the target tissue occurs. Mass spectrometry imaging (MSI) has been recently applied as an innovative tool for detection of molecular distribution of pharmacological agents in heterogeneous targets. This study examined the intra-brain transitivity of alectinib, a novel anaplastic lymphoma kinase inhibitor, using a combination of matrix-assisted laser desorption ionization–MSI and LC-MS/MS techniques. We first analyzed the pharmacokinetic profiles in FVB mice and then examined the effect of the multidrug resistance protein-1 (MDR1) using Mdr1a/b knockout mice including quantitative distribution of alectinib in the brain. While no differences were observed between the mice for the plasma alectinib concentrations, diffuse alectinib distributions were found in the brain of the Mdr1a/b knockout versus FVB mice. These results indicate the potential for using quantitative MSI for clarifying drug distribution in the brain on a microscopic level, in addition to suggesting a possible use in designing studies for anticancer drug development and translational research. PMID:27026287

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 ...

Comparison of doses received by the hippocampus in patients treated with single isocenter– vs multiple isocenter–based stereotactic radiation therapy to the brain for multiple brain metastases

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

Algan, Ozer, E-mail: oalgan@ouhsc.edu; Giem, Jared; Young, Julie

To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)–based or multiple isocenter (MI)–based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A totalmore » of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63 mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V{sub 100}. All of the other measured dosimetric parameters including the V{sub 95}, V{sub 99}, and D{sub 100} were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.« less

Comparison of doses received by the hippocampus in patients treated with single isocenter- vs multiple isocenter-based stereotactic radiation therapy to the brain for multiple brain metastases.

PubMed

Algan, Ozer; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

2015-01-01

To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)-based or multiple isocenter (MI)-based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V100. All of the other measured dosimetric parameters including the V95, V99, and D100 were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Regular aerobic exercise correlates with reduced anxiety and incresed levels of irisin in brain and white adipose tissue.

PubMed

Uysal, Nazan; Yuksel, Oguz; Kizildag, Servet; Yuce, Zeynep; Gumus, Hikmet; Karakilic, Aslı; Guvendi, Guven; Koc, Basar; Kandis, Sevim; Ates, Mehmet

2018-05-29

We have recently shown that regular voluntary aerobic exercised rats have low levels of anxiety. Irisin is an exercise-induced myokine that is produced by many tissues; and the role it plays in anxiolytic behavior is unknown. In this study we aimed to investigate the correlation between anxiety like behavior and irisin levels following regular voluntary aerobic exercise in male mice. We've have shown that anxiety levels decreased in exercised mice, while irisin levels increased in the brain, brown adipose tissue, white adipose tissue, kidney, and pancreas tissues. No significant difference of irisin levels in the liver, muscle and serum were detected in the exercise group, when compared to controls. In addition, there was a strong positive correlation between brain irisin levels and activity in middle area of open field test and in the open arms of elevated plus maze test; both which are indicators of low anxiety levels. Our results suggest that decrease in anxiolytic behavior due to regular voluntary exercise may be associated with locally produced brain irisin. White adipose tissue irisin levels also correlated very strongly with low anxiety. However, no serum irisin increase was detected, ruling out the possibility of increased peripheral irisin levels affecting the brain via the bloodstream. Further research is necessary to explain the mechanisms of which peripheral and central irisin effects anxiety and the brain region affected. Copyright © 2018 Elsevier B.V. All rights reserved.

Implementation of magnetic resonance elastography for the investigation of traumatic brain injuries

NASA Astrophysics Data System (ADS)

Boulet, Thomas

Magnetic resonance elastography (MRE) is a potentially transformative imaging modality allowing local and non-invasive measurement of biological tissue mechanical properties. It uses a specific phase contrast MR pulse sequence to measure induced vibratory motion in soft material, from which material properties can be estimated. Compared to other imaging techniques, MRE is able to detect tissue pathology at early stages by quantifying the changes in tissue stiffness associated with diseases. In an effort to develop the technique and improve its capabilities, two inversion algorithms were written to evaluate viscoelastic properties from the measured displacements fields. The first one was based on a direct algebraic inversion of the differential equation of motion, which decouples under certain simplifying assumptions, and featured a spatio-temporal multi-directional filter. The second one relies on a finite element discretization of the governing equations to perform a direct inversion. Several applications of this technique have also been investigated, including the estimation of mechanical parameters in various gel phantoms and polymers, as well as the use of MRE as a diagnostic tools for brain disorders. In this respect, the particular interest was to investigate traumatic brain injury (TBI), a complex and diverse injury affecting 1.7 million Americans annually. The sensitivity of MRE to TBI was first assessed on excised rat brains subjected to a controlled cortical impact (CCI) injury, before execution of in vivo experiments in mice. MRE was also applied in vivo on mouse models of medulloblastoma tumors and multiple sclerosis. These studies showed the potential of MRE in mapping the brain mechanically and providing non-invasive in vivo imaging markers for neuropathology and pathogenesis of brain diseases. Furthermore, MRE can easily be translatable to clinical settings; thus, while this technique may not be used directly to diagnose different abnormalities in the brain at this time, it may be helpful to detect abnormalities, follow therapies, and trace macroscopic changes that are not seen by conventional methods with clinical relevance.

Association between polychlorinated biphenyls and Parkinson's disease neuropathology.

PubMed

Hatcher-Martin, Jaime M; Gearing, Marla; Steenland, Kyle; Levey, Allan I; Miller, Gary W; Pennell, Kurt D

2012-10-01

Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson's disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson's disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson's disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson's disease patients. When stratified by sex, the female Parkinson's disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson's disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson's disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson's disease, including greater susceptibility of females. Copyright © 2012 Elsevier Inc. All rights reserved.

Association between polychlorinated biphenyls and Parkinson’s disease neuropathology

PubMed Central

Hatcher-Martin, Jaime M.; Gearing, Marla; Steenland, Kyle; Levey, Allan I.; Miller, Gary W.; Pennell, Kurt D.

2012-01-01

Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson’s disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson’s disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson’s disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson’s disease patients. When stratified by sex, the female Parkinson’s disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson’s disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson’s disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson’s disease, including greater susceptibility of females. PMID:22906799

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

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.

The biochemical, nanomechanical and chemometric signatures of brain cancer.

PubMed

Abramczyk, Halina; Imiela, Anna

2018-01-05

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 2845cm -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 75.7kPa, and the mean of 27.16kPa. 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. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.