WorldWideScience

Sample records for brain tissue transplantation

  1. Enhancement of Sexual Behavior in Female Rats by Neonatal Transplantation of Brain Tissue from Males

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  3. Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation.

    Science.gov (United States)

    Vargas, Hugo E; Laskus, Tomasz; Radkowski, Marek; Wilkinson, Jeff; Balan, Vijay; Douglas, David D; Harrison, M Edwyn; Mulligan, David C; Olden, Kevin; Adair, Debra; Rakela, Jorge

    2002-11-01

    Patients with chronic hepatitis C frequently report tiredness, easy fatigability, and depression. The aim of this study is to determine whether hepatitis C virus (HCV) replication could be found in brain tissue in patients with hepatitis C and depression. We report two patients with recurrent hepatitis C after liver transplantation who also developed severe depression. One patient died of multiorgan failure and the other, septicemia caused by Staphylococcus aureussis. Both patients had evidence of severe hepatitis C recurrence with features of cholestatic fibrosing hepatitis. We were able to study samples of their central nervous system obtained at autopsy for evidence of HCV replication. The presence of HCV RNA-negative strand, which is the viral replicative form, was determined by strand-specific Tth-based reverse-transcriptase polymerase chain reaction. Viral sequences were compared by means of single-strand conformation polymorphism and direct sequencing. HCV RNA-negative strands were found in subcortical white matter from one patient and cerebral cortex from the other patient. HCV RNA-negative strands amplified from brain tissue differed by several nucleotide substitutions from serum consensus sequences in the 5' untranslated region. These findings support the concept of HCV neuroinvasion, and we speculate that it may provide a biological substrate to neuropsychiatric disorders observed in patients with chronic hepatitis C. The exact lineage of cells permissive for HCV replication and the possible interaction between viral replication and cerebral function that may lead to depression remain to be elucidated.

  4. Intrinsic control of electroresponsive properties of transplanted mammalian brain neurons

    DEFF Research Database (Denmark)

    Hounsgaard, J; Yarom, Y

    1985-01-01

    The present study presents the first analysis of neurons in mammalian brain transplants based on intracellular recording. The results, obtained in brain slices including both donor and host tissue, showed that neuronal precursor cells in embryonic transplants retained their ability to complete th...

  5. Banking brain tissue for research

    NARCIS (Netherlands)

    Klioueva, Natasja; Bovenberg, Jasper; Huitinga, I.

    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

  6. TRANSPLANTATION AND POTENTIAL IMMORTALITY OF MAMMALIAN TISSUES

    Science.gov (United States)

    Loeb, Leo

    1926-01-01

    1. Serial transplantation of tumors made it possible in 1901 and following years to draw the conclusion that various mammalian tissues have potential immortality. Serial transplantations of normal tissues did not succeed at first, because the homoioreaction on the part of the lymphocytes and connective tissue of the host injures the transplant. 2. In continuation of these experiments we found that cartilage of the rat can be transplanted serially to other rats at least for a period of 3 years. At the end of that time great parts of the transplanted cartilage and perichondrium are alive. 3. Not only the cartilage of young rats can be homoiotransplanted, but also the cartilage of very old rats which are nearing the end of life. By using such animals we have been able to obtain cartilage and perichondrium approaching an age of 6 years which is almost double the average age of a rat. 4. We found that cartilage can be homoiotransplanted more readily than other tissues for the following reasons: (a) While in principle the homoioreaction towards cartilage is the same as against other tissues, cartilage elicits this reaction with less intensity; (b) cartilage is better able to resist the invasion of lymphocytes and connective tissue than the majority of other tissues; (c) a gradual adaptation between transplant and host seems to take place in the case of cartilage transplantation, as a result of which the lymphocytic reaction on the part of the host tissue decreases progressively the longer the cartilage is kept in the strange host. 5. At time of examination we not only found living transplanted cartilage tissue, but also perichondrial tissue, which in response to a stimulus apparently originating in the necrotic central cartilage, had been proliferating and replacing it. These results suggest that it may perhaps be possible under favorable conditions to keep cartilage alive indefinitely through serial transplantations. 6. At the same time these experiments permit the

  7. Live birth after ovarian tissue transplant

    Science.gov (United States)

    Lee, D. M.; Yeoman, R. R.; Battaglia, D. E.; Stouffer, R. L.; Zelinski-Wooten, M. B.; Fanton, J. W.; Wolf, D. P.

    2004-03-01

    Radiation and high-dose chemotherapy may render women with cancer prematurely sterile, a side-effect that would be avoided if ovarian tissue that had been removed before treatment could be made to function afterwards. Live offspring have been produced from transplanted ovarian tissue in mice and sheep but not in monkeys or humans, although sex steroid hormones are still secreted. Here we describe the successful transplantation of fresh ovarian tissue to a different site in a monkey, which has led to the birth of a healthy female after oocyte production, fertilization and transfer to a surrogate mother. The ectopically grafted tissue functions without surgical connection to major blood vessels and sets the stage for the transplantation of cryopreserved ovarian tissue in humans.

  8. Differentiation and Cell-Cell Interactions of Neural Progenitor Cells Transplanted into Intact Adult Brain.

    Science.gov (United States)

    Sukhinich, K K; Kosykh, A V; Aleksandrova, M A

    2015-11-01

    We studied the behavior and cell-cell interactions of embryonic brain cell from GFP-reporter mice after their transplantation into the intact adult brain. Fragments or cell suspensions of fetal neocortical cells at different stages of development were transplanted into the neocortex and striatum of adult recipients. Even in intact brain, the processes of transplanted neurons formed extensive networks in the striatum and neocortical layers I and V-VI. Processes of transplanted cells at different stages of development attained the rostral areas of the frontal cortex and some of them reached the internal capsule. However, the cells transplanted in suspension had lower process growth potency than cells from tissue fragments. Tyrosine hydroxylase fibers penetrated from the recipient brain into grafts at both early and late stages of development. Our experiments demonstrated the formation of extensive reciprocal networks between the transplanted fetal neural cells and recipient brain neurons even in intact brain.

  9. Planarian immobilization, partial irradiation, and tissue transplantation.

    Science.gov (United States)

    Guedelhoefer, Otto C; Sánchez Alvarado, Alejandro

    2012-08-06

    The planarian, a freshwater flatworm, has proven to be a powerful system for dissecting metazoan regeneration and stem cell biology. Planarian regeneration of any missing or damaged tissues is made possible by adult stem cells termed neoblasts. Although these stem cells have been definitively shown to be pluripotent and singularly capable of reconstituting an entire animal, the heterogeneity within the stem cell population and the dynamics of their cellular behaviors remain largely unresolved. Due to the large number and wide distribution of stem cells throughout the planarian body plan, advanced methods for manipulating subpopulations of stem cells for molecular and functional study in vivo are needed. Tissue transplantation and partial irradiation are two methods by which a subpopulation of planarian stem cells can be isolated for further study. Each technique has distinct advantages. Tissue transplantation allows for the introduction of stem cells, into a naïve host, that are either inherently genetically distinct or have been previously treated pharmacologically. Alternatively, partial irradiation allows for the isolation of stem cells within a host, juxtaposed to tissue devoid of stem cells, without the introduction of a wound or any breech in tissue integrity. Using these two methods, one can investigate the cell autonomous and non-autonomous factors that control stem cell functions, such as proliferation, differentiation, and migration. Both tissue transplantation and partial irradiation have been used historically in defining many of the questions about planarian regeneration that remain under study today. However, these techniques have remained underused due to the laborious and inconsistent nature of previous methods. The protocols presented here represent a large step forward in decreasing the time and effort necessary to reproducibly generate large numbers of grafted or partially irradiated animals with efficacies approaching 100 percent. We cover the

  10. Tissue-intrinsic dysfunction of circadian clock confers transplant arteriosclerosis.

    Science.gov (United States)

    Cheng, Bo; Anea, Ciprian B; Yao, Lin; Chen, Feng; Patel, Vijay; Merloiu, Ana; Pati, Paramita; Caldwell, R William; Fulton, David J; Rudic, R Daniel

    2011-10-11

    The suprachiasmatic nucleus of the brain is the circadian center, relaying rhythmic environmental and behavioral information to peripheral tissues to control circadian physiology. As such, central clock dysfunction can alter systemic homeostasis to consequently impair peripheral physiology in a manner that is secondary to circadian malfunction. To determine the impact of circadian clock function in organ transplantation and dissect the influence of intrinsic tissue clocks versus extrinsic clocks, we implemented a blood vessel grafting approach to surgically assemble a chimeric mouse that was part wild-type (WT) and part circadian clock mutant. Arterial isografts from donor WT mice that had been anastamosed to common carotid arteries of recipient WT mice (WT:WT) exhibited no pathology in this syngeneic transplant strategy. Similarly, when WT grafts were anastamosed to mice with disrupted circadian clocks, the structural features of the WT grafts immersed in the milieu of circadian malfunction were normal and absent of lesions, comparable to WT:WT grafts. In contrast, aortic grafts from Bmal1 knockout (KO) or Period-2,3 double-KO mice transplanted into littermate control WT mice developed robust arteriosclerotic disease. These lesions observed in donor grafts of Bmal1-KO were associated with up-regulation in T-cell receptors, macrophages, and infiltrating cells in the vascular grafts, but were independent of hemodynamics and B and T cell-mediated immunity. These data demonstrate the significance of intrinsic tissue clocks as an autonomous influence in experimental models of arteriosclerotic disease, which may have implications with regard to the influence of circadian clock function in organ transplantation.

  11. [Growth inhibition of embryonic tissues transplanted to syngeneic newborn recipients].

    Science.gov (United States)

    Zinzar, S N; Karmanova NVa; Svet-Moldavskiĭ, G I

    1976-01-01

    Skin grafts of embryos and teratomas formed after the transplantation of ground tissues of embryos (18-20 day and 12-14-day) to neonatal syngeneic recipients were studied; it appeared that their growth was considerably delayed in comparison with analogous transplants in adult recipients. It is supposed that the organism of embryos and neonates has factors controlling the growth of embryonic tissues.

  12. The safety of transplanting cryopreserved ovarian tissue in cancer patients

    DEFF Research Database (Denmark)

    Rosendahl, Mikkel; Greve, Tine; Andersen, Claus Yding

    2013-01-01

    Transplantation of frozen/thawed ovarian tissue from patients with a malignant condition is associated with a risk of re-introduction of the disease as the tissue usually is removed before anti-cancer therapy and may thus contain malignant cells. We review studies investigating the presence of ma...... of malignant cells in cryopreserved ovarian tissue from patients with malignant disease and based on the strength of the evidence, recommendations for transplantations are proposed....

  13. Tissue and organ donation and transplantation in Iran.

    Science.gov (United States)

    Goodarzi, Parisa; Aghayan, Hamid Reza; Larijani, Bagher; Rafiee, Alireza Baradaran; Falahzadeh, Khadijeh; Sahebjam, Mehrnaz; Ghaderi, Firoozeh; Arjmand, Babak

    2015-06-01

    Tissue and organ transplantation is one of the most promising treatments for some incurable diseases. Nowadays, transplantation is the common therapy in many countries. Unfortunately, availability of donated tissues and organs is limited. There are several factors which may affect donation rate for instance; social factors, culture, religion, and family decision. Accordingly, religious beliefs have a crucial role in tissue and organ donation and transplantation. Islam as a code of life has a comprehensive road map to lead mankind. Spiritual view of human life is considered to be much more valuable in Islam. Therefore, saving a human life is one of the most important Islamic teachings. In Iran as a Muslim country, tissue and organ transplantation program was established based on religious scholars' permission which has an essential role towards considerable development of the program in Iran.

  14. Transplantation of Cadaver Tissues and Organs. Part 15. Chapter 338

    Science.gov (United States)

    1984-01-09

    who provides cadaveric tissues and organs to transplantation surgeons. During the agonal days of a patient’s course, the family and neurosurgeon...Amendments of 1976. METHODS OF STERILIZATION OF TISSUES 45 Donald J. Prolo, M.D. Tissues for implantation must rigorously be free of contaminating bacteria

  15. Long-term function of ovarian tissue transplants

    Directory of Open Access Journals (Sweden)

    Sherman J. Silber

    2012-12-01

    Full Text Available The long term duration of function of ovarian cortical tissue grafts is reviewed in this paper by describing cases of restoration of fertility by transplant of ovarian cortical tissue from matching donors where the recipient was in need of the transplant due to sterilizing effects of leukemia, premature ovarian failure (POF, and to reflect that it may be possible to postpone the normal time of menopause or to alleviate its symptoms.

  16. Immediate tissue transplantation in upper limb trauma: spare parts reconstruction.

    Science.gov (United States)

    Lin, Chih Hung; Webb, Kelli; Neumeister, Michael W

    2014-07-01

    The management of mutilated upper extremity wounds offers challenges for all hand surgeons. Loss of composite tissues usually requires grafts or flaps to gain coverage and restore function. Nonsalvagable digits or amputated parts are a source of spare tissues that can be used for reconstruction of the hand or limb. Immediate tissue transplantation is a resourceful technique for hand surgeons to limit donor morbidity while making the most out of a terrible injury to the hand or upper extremity. This article reviews the various methods by which immediate tissue transplantation can be employed in hand trauma. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Hypoalbuminaemia in brain-dead donors for liver transplantation

    African Journals Online (AJOL)

    Nicky

    We retrospectively reviewed the charts of the 37 brain-dead patients referred to the organ transplant unit at Groote. Schuur Hospital in 2001 and 2002 as potential donors for liver transplantation. All potential donors were assessed, investigated and man- aged according to standard protocols. The assessment con- sisted of ...

  18. Simultaneous transplantation of fetal ventral mesencephalic tissue and encapsulated genetically modified cells releasing GDNF in a hemi-parkinsonian rat model of Parkinson's disease

    DEFF Research Database (Denmark)

    Perez-Bouza, Alberto; Di Santo, Stefano; Seiler, Stefanie

    2017-01-01

    Transplantation of fetal ventral mesencephalic (VM) neurons for Parkinson's disease (PD) is limited by poor survival and suboptimal integration of grafted tissue into the host brain. In a 6-OHDA rat model of PD we investigated the feasibility of simultaneous transplantation of rat fetal VM tissue...

  19. Alterações fisiológicas da morte encefálica em potenciais doadores de órgãos e tecidos para transplantes Los cambios fisiológicos de la muerte cerebral en potenciales donadores de órganos y tejidos para trasplante Physiological changes of brain death in potential donors of organs and tissues for transplantation

    Directory of Open Access Journals (Sweden)

    Sarah Gabriel Freire

    2012-12-01

    órnea (3,1%. Se cree que el conocimiento de estos cambios permite al equipo de atención de la salud dirigir sus acciones al potencial donador de acuerdo a sus necesidades y así mantener los órganos/tejidos viables para el trasplante.The objective was to describe the physiologic changes of brain death in potential donors of organs and tissues for transplantation. Exploratory descriptive study with prospective data and quantitative approach carried out in emergency and intensive care units hospital adult, in the period from April to October 2011. The population consisted of 32 potential donors of organs and tissues for transplantation. After approval of Ethics Committee, data were collected, tabulated and analyzed by descriptive statistics by SPSS 15.0 software and presented in tables. Physiological changes were: hypotension (100%, hypothermia (75%, hypernatremia (62,5%, diabetes insipidus (37,5%, hyperglycemia (32,3%, infection (25,0%, hypertension (9,4% and corneal ulcer (3,1%. It was found that knowledge of these changes allows the team of health care to direct the potential donors according to their needs and thus keep the organ/tissue viable for transplant.

  20. The donor management algorithm in transplantation of a composite facial tissue allograft.. First experience in Russia

    Directory of Open Access Journals (Sweden)

    V. V. Uyba

    2016-01-01

    Full Text Available In the period from 2005 to December 2015, 37 transplantations of vascularized composite facial tissue allografts (VCAs were performed in the world. A vascularized composite tissue allotransplantation has been recognized as a solid organ transplantation rather than a special kind of tissue transplantation. The recent classification of composite tissue allografts into the category of donor organs gave rise to a number of organizational, ethical, legal, technical, and economic problems. In May 2015, the first successful transplantation of a composite facial tissue allograft was performed in Russia. The article describes our experience of multiple team interactions at donor management stage when involved in the identification, conditioning, harvesting, and delivering donor organs to various hospitals. A man, aged 51 years old, diagnosed with traumatic brain injury became a donor after the diagnosis of brain deathhad been made, his death had been ascertained, and the requested consent for organ donation had been obtained from relatives. At donor management stage, a tracheostomy was performed and a posthumous facial mask was molded. The "face first, concurrent completion" algorithm was chosen for organ harvesting and facial VCA procurement; meanwhile, the facial allograft was procured as the "full face" category. The total surgery duration from the incision to completing the procurement (including that of solid organs made 8 hours 20 minutes. Immediately after the procurement, the facial VCA complex was sent to the St. Petersburg clinic by medical aircraft transportation, and was there transplanted 9 hours later. Donor kidneys were transported to Moscow bycivil aviation and transplanted 17 and 20 hours later. The authors believe that this clinical case report demonstrates the feasibility and safety of multiple harvesting of solid organs and a vascularized composite facial tissue allograft. However, this kind of surgery requires an essential

  1. The role of the transplant coordinator on tissue donation in Turkey.

    Science.gov (United States)

    Yücetin, L; Keçecioğlu, N; Ozenci, A M; Söğüncü, Y; Islamoğlu, K; Ersoy, F F

    2004-01-01

    While solid organs represent the dramatic and lifesaving aspect of donation after death, the transplantation of tissues from donors after death is a much larger-scale activity that benefits enormous numbers of patients, usually in a life-enhancing rather than a lifesaving manner. Some types of tissue transplantation, such as heart valve and cornea transplantation, have been established for many decades and are reasonably well understood by health professionals and the public. Many other types of tissue donation, such as bone, skin, tendons, etc, are much less well known but nonetheless result in beneficial treatment for large numbers of patients. Skin is used to prevent fluid loss and infection following a major burn; bone is used to improve the clinical success of a range of orthopedic operations, such as joint replacements, spinal fusions, and reconstructions following trauma or tumor. In the United States more than 20,000 donors provided cadaveric tissue in 1999, compared to 6,000 in 1994. We ask all families of brain-dead donors for consent for tissue donation. Between January 1, 1999, and January 3, 2003, we had 58 actual cadaveric donors, procuring three skins, 15 tendons, six bones, 13 heart valves, and 40 corneas. We performed three skin, 40 tendon, and three bone transplants as well as storing other tissues. One donor can give health to 50 different recipients. In general, the argument runs for a transplant coordinator "if you can do it, then you must." We can save lives and present a better quality of life with solid organ and tissue donation.

  2. Visceral adipose tissue is associated with microstructural brain tissue damage.

    Science.gov (United States)

    Widya, Ralph L; Kroft, Lucia J M; Altmann-Schneider, Irmhild; van den Berg-Huysmans, Annette A; van der Bijl, Noortje; de Roos, Albert; Lamb, Hildo J; van Buchem, Mark A; Slagboom, P Eline; van Heemst, Diana; van der Grond, Jeroen

    2015-05-01

    Obesity has been associated with microstructural brain tissue damage. Different fat compartments demonstrate different metabolic and endocrine behaviors. The aim was to investigate the individual associations between abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and microstructural integrity in the brain. This study comprised 243 subjects aged 65.4 ± 6.7 years. The associations between abdominal VAT and SAT, assessed by CT, and magnetization transfer imaging markers of brain microstructure for gray and white matter were analyzed and adjusted for confounding factors. VAT was associated with normalized MTR peak height in gray (β -0.216) and white matter (β -0.240) (both P  0.05). Stepwise linear regression analysis showed that only VAT was associated with normalized MTR peak height in gray and white matter (both P VAT rather than SAT is associated with microstructural brain tissue damage in elderly individuals. © 2015 The Obesity Society.

  3. Knowledge and opinions about tissue donation and transplantation among Polish students and physicians.

    Science.gov (United States)

    Olender, Ewa; Palczynska, Anna; Rykowski, Michal; Uhrynowska-Tyszkiewicz, Izabela; Kaminski, Artur

    2010-05-01

    The idea of transplantation seems to be commonly identified by lay and professional people only with transplantation of vascularized organs like kidney or heart. The question arises whether there is any awareness of tissue transplantation among the public. A survey was therefore undertaken to assess awareness of and approaches to tissue donation and transplantation among selected social groups. A questionnaire on donation and transplantation issues was administered to respondents from the following groups: secondary school students, non-medical university students, medical university students, physicians. On the whole, 441 non-randomly sampled respondents were surveyed. The awareness of tissue transplantation is narrower than the awareness of organ transplantation. The support for tissue transplantation is weaker than for organ transplantation. This study shows that there is an acute need for education in the legal aspects of transplantation and that ways of motivating healthcare professionals to promote transplantation should be developed.

  4. Evaluation of the ovarian reserve in women transplanted with frozen and thawed ovarian cortical tissue

    DEFF Research Database (Denmark)

    Greve, Tine; Schmidt, Kirsten Tryde; Kristensen, Stine Gry

    2012-01-01

    To investigate ovarian reserve and ovarian function in women transplanted with frozen/thawed ovarian tissue.......To investigate ovarian reserve and ovarian function in women transplanted with frozen/thawed ovarian tissue....

  5. Cryopreservation, Culture, and Transplantation of Human Fetal Mesencephalic Tissue into Monkeys

    Science.gov (United States)

    Redmond, D. E.; Naftolin, F.; Collier, T. J.; Leranth, C.; Robbins, R. J.; Sladek, C. D.; Roth, R. H.; Sladek, J. R.

    1988-11-01

    Studies in animals suggest that fetal neural grafts might restore lost neurological function in Parkinson's disease. In monkeys, such grafts survive for many months and reverse signs of parkinsonism, without attendant graft rejection. The successful and reliable application of a similar transplantation procedure to human patients, however, will require neural tissue obtained from human fetal cadavers, with demonstrated cellular identity, viability, and biological safety. In this report, human fetal neural tissue was successfully grafted into the brains of monkeys. Neural tissue was collected from human fetal cadavers after 9 to 12 weeks of gestation and cryopreserved in liquid nitrogen. Viability after up to 2 months of storage was demonstrated by cell culture and by transplantation into monkeys. Cryopreservation and storage of human fetal neural tissue would allow formation of a tissue bank. The stored cells could then be specifically tested to assure their cellular identity, viability, and bacteriological and virological safety before clinical use. The capacity to collect and maintain viable human fetal neural tissue would also facilitate research efforts to understand the development and function of the human brain and provide opportunities to study neurological diseases.

  6. Uterine Tissue Engineering and the Future of Uterus Transplantation.

    Science.gov (United States)

    Hellström, Mats; Bandstein, Sara; Brännström, Mats

    2017-07-01

    The recent successful births following live donor uterus transplantation are proof-of-concept that absolute uterine factor infertility is a treatable condition which affects several hundred thousand infertile women world-wide due to a dysfunctional uterus. This strategy also provides an alternative to gestational surrogate motherhood which is not practiced in most countries due to ethical, religious or legal reasons. The live donor surgery involved in uterus transplantation takes more than 10 h and is then followed by years of immunosuppressive medication to prevent uterine rejection. Immunosuppression is associated with significant adverse side effects, including nephrotoxicity, increased risk of serious infections, and diabetes. Thus, the development of alternative approaches to treat absolute uterine factor infertility would be desirable. This review discusses tissue engineering principles in general, but also details strategies on how to create a bioengineered uterus that could be used for transplantation, without risky donor surgery and any need for immunosuppression. We discuss scaffolds derived from decellularized organs/tissues which may be recellularized using various types of autologous somatic/stem cells, in particular for uterine tissue engineering. It further highlights the hurdles that lay ahead in developing an alternative to an allogeneic source for uterus transplantation.

  7. 21 CFR 1270.21 - Determination of donor suitability for human tissue intended for transplantation.

    Science.gov (United States)

    2010-04-01

    ... tissue intended for transplantation. 1270.21 Section 1270.21 Food and Drugs FOOD AND DRUG ADMINISTRATION... FOOD AND DRUG ADMINISTRATION HUMAN TISSUE INTENDED FOR TRANSPLANTATION Donor Screening and Testing § 1270.21 Determination of donor suitability for human tissue intended for transplantation. (a) Donor...

  8. Intra-Hospital Committee for Donation of Organs and Tissues for Transplant: ethical issues

    Directory of Open Access Journals (Sweden)

    Josiane Cappellaro

    2015-02-01

    Full Text Available The objective of this study was to demonstrate ethical aspects involved in the donation, collection and transplantation of organs and tissues through the experiences of workers in an intra-hospital committee for donation of organs and tissues for transplant. Exploratory qualitative research developed with eleven health workers. Data collection was performed at a university hospital in Pelotas, RS, Brazil, in the period of January-March 2010, through interviews. Data analysis resulted in the following categories: understanding of brain death diagnosis as an ethical issue; and, ethical issues experienced by workers in the relationship established with the family. It was concluded that such situations instigate workers to reflect on their attitudes, values, and their role as a health team member and protector of lives.

  9. Matrix-Assisted Transplantation of Functional Beige Adipose Tissue

    OpenAIRE

    Tharp, Kevin M.; Jha, Amit K.; Kraiczy, Judith; Yesian, Alexandra; Karateev, Grigory; Sinisi, Riccardo; Dubikovskaya, Elena A.; Healy, Kevin E.; Stahl, Andreas

    2015-01-01

    Novel, clinically relevant, approaches to shift energy balance are urgently needed to combat metabolic disorders such as obesity and diabetes. One promising approach has been the expansion of brown adipose tissues that express uncoupling protein (UCP) 1 and thus can uncouple mitochondrial respiration from ATP synthesis. While expansion of UCP1-expressing adipose depots may be achieved in rodents via genetic and pharmacological manipulations or the transplantation of brown fat depots, these me...

  10. Temperature Effects on Brain Tissue in Compression

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael; 10.1016/j.jmbbm.2012.04.005

    2013-01-01

    Extensive research has been carried out for at least 50 years to understand the mechanical properties of brain tissue in order to understand the mechanisms of traumatic brain injury (TBI). The observed large variability in experimental results may be due to the inhomogeneous nature of brain tissue and to the broad range of test conditions. However, test temperature is also considered as one of the factors influencing the properties of brain tissue. In this research, the mechanical properties of porcine brain have been investigated at 22C (room temperature) and at 37C (body temperature) while maintaining a constant preservation temperature of approximately 4-5C. Unconfined compression tests were performed at dynamic strain rates of 30 and 50/s using a custom made test apparatus. There was no significant difference (p = 0.8559 - 0.9290) between the average engineering stresses of the brain tissue at the two different temperature conditions. The results of this study should help to understand the behavior of bra...

  11. Simultaneous Transplantation of Fetal Ventral Mesencephalic Tissue and Encapsulated Genetically Modified Cells Releasing GDNF in a Hemi-Parkinsonian Rat Model of Parkinson's Disease.

    Science.gov (United States)

    Perez-Bouza, Alberto; Di Santo, Stefano; Seiler, Stefanie; Meyer, Morten; Andereggen, Lukas; Huber, Alexander; Guzman, Raphael; Widmer, Hans R

    2017-09-01

    Transplantation of fetal ventral mesencephalic (VM) neurons for Parkinson's disease (PD) is limited by poor survival and suboptimal integration of grafted tissue into the host brain. In a 6-hydroxydopamine rat model of PD, we investigated the feasibility of simultaneous transplantation of rat fetal VM tissue and polymer-encapsulated C2C12 myoblasts genetically modified to produce glial cell line-derived neurotrophic factor (GDNF) or mock-transfected myoblasts on graft function. Amphetamine-induced rotations were assessed prior to transplantation and 2, 4, 6 and 9 wk posttransplantation. We found that rats grafted with VM transplants and GDNF capsules showed a significant functional recovery 4 wk after implantation. In contrast, rats from the VM transplant and mock-capsule group did not improve at any time point analyzed. Moreover, we detected a significantly higher number of tyrosine hydroxylase immunoreactive (TH-ir) cells per graft (2-fold), a tendency for a larger graft volume and an overall higher TH-ir fiber outgrowth into the host brain (1.7-fold) in the group with VM transplants and GDNF capsules as compared to the VM transplant and mock-capsule group. Most prominent was the TH-ir fiber outgrowth toward the capsule (9-fold). Grafting of GDNF-pretreated VM transplants in combination with the implantation of GDNF capsules resulted in a tendency for a higher TH-ir fiber outgrowth into the host brain (1.7-fold) as compared to the group transplanted with untreated VM transplants and GDNF capsules. No differences between groups were observed for the number of surviving TH-ir neurons or graft volume. In conclusion, our findings demonstrate that simultaneous transplantation of fetal VM tissue and encapsulated GDNF-releasing cells is feasible and support the graft survival and function. Pretreatment of donor tissue with GDNF may offer a way to further improve cell transplantation approaches for PD.

  12. Simultaneous transplantation of fetal ventral mesencephalic tissue and encapsulated genetically modified cells releasing GDNF in a hemi-parkinsonian rat model of Parkinson's disease

    DEFF Research Database (Denmark)

    Perez-Bouza, Alberto; Di Santo, Stefano; Seiler, Stefanie

    2017-01-01

    between groups were observed for the number of surviving TH-ir neurons or graft volume. In conclusion, our findings demonstrate that simultaneous transplantation of fetal VM tissue and encapsulated GDNF-releasing cells is feasible and support the graft survival and function. Pre-treatment of donor tissue......Transplantation of fetal ventral mesencephalic (VM) neurons for Parkinson's disease (PD) is limited by poor survival and suboptimal integration of grafted tissue into the host brain. In a 6-OHDA rat model of PD we investigated the feasibility of simultaneous transplantation of rat fetal VM tissue...... and polymer-encapsulated C2C12 myoblasts genetically modified to produce glial cell line-derived neurotrophic factor or mocktransfected myoblasts on graft function. Amphetamine-induced rotations were assessed prior and 2, 4, 6 and 9 weeks post-transplantation. We found that rats grafted with VM transplants...

  13. Long-term duration of function of ovarian tissue transplants

    DEFF Research Database (Denmark)

    Andersen, Claus Yding; Silber, Sherman J; Berghold, Stinne Holm

    2012-01-01

    These three case reports describe the long-term duration of function of ovarian cortical tissue grafts among patients in a university fertility preservation programme in Europe and in a private practice programme in the USA. One woman underwent sterilizing cancer treatment and had frozen ovarian...... (repeatedly in some cases) of cryopreserved ovarian tissue has restored reproductive function to all other women in the study centres' programmes for some years. The sustained longevity of function of the transplanted tissue suggests that it may also be possible to postpone the normal time of menopause...... or to alleviate its symptoms. These three case reports describe the long-term duration of function of ovarian cortical tissue grafts among patients in a university fertility preservation programme in Europe and in a private practice programme in the USA. One woman underwent sterilizing cancer treatment and had...

  14. Tissue-engineered epithelium transplantation for severe ocular surface burns.

    Science.gov (United States)

    Guo, Qing; Pi, Yuli; Dong, Ying; Zhu, Jing

    2013-03-01

    To evaluate the clinical outcomes of tissue-engineered epithelium transplantation for severe ocular surface burns. This was a retrospective observational case series. From October 2005 to May 2011, 19 eyes of 19 patients with grade IV to VI ocular surface burns (Dua Classification) were treated by autologous transplantation of corneal stem cells cultivated on a fibrin gel membrane, with a mean follow-up of 16.2 months (range 12-36 months). Postoperative corneal surface stability, visual acuity (VA), corneal opacity, and neovascularization were evaluated. No corneal perforations occurred and the entire corneal surface was free from epithelial defects in all eyes. At the final follow-up visit, VA in 17 eyes was improved after surgery, with 6 eyes achieving a VA of 20/100 or better. Corneal vascularization was significantly reduced in 17 (89.5%) eyes. Corneal opacity was also improved in 12 (63.2%) eyes. All donor eyes remained healthy. Tissue-engineered epithelium transplantation can promote rapid reepithelialization of the ocular surface, inhibit corneal neovascularization, and improve vision for patients with severe ocular surface burns.

  15. Current Status and Future Development of Cell Transplantation Therapy for Periodontal Tissue Regeneration

    OpenAIRE

    Yoshida, Toshiyuki; Washio, Kaoru; Iwata, Takanori; Okano, Teruo; Ishikawa, Isao

    2012-01-01

    It has been shown that stem cell transplantation can regenerate periodontal tissue, and several clinical trials involving transplantation of stem cells into human patients have already begun or are in preparation. However, stem cell transplantation therapy is a new technology, and the events following transplantation are poorly understood. Several studies have reported side effects and potential risks associated with stem cell transplantation therapy. To protect patients from such risks, gove...

  16. Identification, tissue distribution and evaluation of brain ...

    Indian Academy of Sciences (India)

    Prakash

    mechanisms regulating feeding in order to improve its performance in captivity. The objectives of this study were to clone NPY cDNA, evaluate the mRNA levels in different tissues of flounder, and also evaluate brain NPY expression to associate food intake with NPY expression levels. A 597 bp NPY cDNA was cloned from ...

  17. Modelling Brain Tissue using Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Dyrby, Tim Bjørn

    2008-01-01

    Diffusion MRI, or diffusion weighted imaging (DWI), is a technique that measures the restricted diffusion of water molecules within brain tissue. Different reconstruction methods quantify water-diffusion anisotropy in the intra- and extra-cellular spaces of the neural environment. Fibre tracking...

  18. Histomorphological Evaluation of Fresh Ovarian Tissue Transplanted Into Back Muscles of Balb/C Mice

    Directory of Open Access Journals (Sweden)

    I Amiri

    2011-06-01

    Full Text Available & objectives: Today, different methods for maintaining reproductive capability in young women with cancer are being considered. One of the most prominent of these methods is ovarian tissue transplant. Despite the relative success of this method, the appropriate location and methods of transplantation is still a matter of discussion. The present study evaluated the histomorphology of fresh ovarian tissue transplantation by two methods, inter muscular and intra muscular, in Balb/C mice. Methods & Materials: The study was conducted at Hamedan University of Medical Sciences in 2009. Fresh ovarian tissues from 12-14 day old Balb/C mice were transplanted into back muscles of ovarectomized 6 week old Balb/C mice both intermuscularly and intramuscularly. All transplanted mice received intra-peritoneal injections of a unit of rFSH for 4 weeks, every other day. At the end of the tenth week, all transplant recipient mice were killed and the transplanted ovarian tissues were removed. All samples were assessed for the angiogenesis and viability of follicles. Data were analyzed using SPSS software, using independent t- test. Results: In intermuscular transplanted group, the transplanted tissues were rejected in two cases. In the sections prepared from the other cases, in spite of the presence of some small necrotic areas, the majority of ovarian tissues had a healthy appearance within the primordial, primary, secondary and antral follicles. Apart from a significant reduction in the number of follicles and smaller size of follicles in the transplanted tissue in comparison with control group, no other major differences in morphology, histology, and the process of maturation of ovarian follicles were observed between the transplanted and control groups. Conclusion: Fresh ovarian tissue transplantation into muscles of the back area without basic vascular pedicle has new angiogenesis capabilities, appropriate survival and development of primordial follicles and

  19. Metabolomics studies in brain tissue: A review.

    Science.gov (United States)

    Gonzalez-Riano, Carolina; Garcia, Antonia; Barbas, Coral

    2016-10-25

    Brain is still an organ with a composition to be discovered but beyond that, mental disorders and especially all diseases that curse with dementia are devastating for the patient, the family and the society. Metabolomics can offer an alternative tool for unveiling new insights in the discovery of new treatments and biomarkers of mental disorders. Until now, most of metabolomic studies have been based on biofluids: serum/plasma or urine, because brain tissue accessibility is limited to animal models or post mortem studies, but even so it is crucial for understanding the pathological processes. Metabolomics studies of brain tissue imply several challenges due to sample extraction, along with brain heterogeneity, sample storage, and sample treatment for a wide coverage of metabolites with a wide range of concentrations of many lipophilic and some polar compounds. In this review, the current analytical practices for target and non-targeted metabolomics are described and discussed with emphasis on critical aspects: sample treatment (quenching, homogenization, filtration, centrifugation and extraction), analytical methods, as well as findings considering the used strategies. Besides that, the altered analytes in the different brain regions have been associated with their corresponding pathways to obtain a global overview of their dysregulation, trying to establish the link between altered biological pathways and pathophysiological conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Mechanical characterization of human brain tissue.

    Science.gov (United States)

    Budday, S; Sommer, G; Birkl, C; Langkammer, C; Haybaeck, J; Kohnert, J; Bauer, M; Paulsen, F; Steinmann, P; Kuhl, E; Holzapfel, G A

    2017-01-15

    Mechanics are increasingly recognized to play an important role in modulating brain form and function. Computational simulations are a powerful tool to predict the mechanical behavior of the human brain in health and disease. The success of these simulations depends critically on the underlying constitutive model and on the reliable identification of its material parameters. Thus, there is an urgent need to thoroughly characterize the mechanical behavior of brain tissue and to identify mathematical models that capture the tissue response under arbitrary loading conditions. However, most constitutive models have only been calibrated for a single loading mode. Here, we perform a sequence of multiple loading modes on the same human brain specimen - simple shear in two orthogonal directions, compression, and tension - and characterize the loading-mode specific regional and directional behavior. We complement these three individual tests by combined multiaxial compression/tension-shear tests and discuss effects of conditioning and hysteresis. To explore to which extent the macrostructural response is a result of the underlying microstructural architecture, we supplement our biomechanical tests with diffusion tensor imaging and histology. We show that the heterogeneous microstructure leads to a regional but not directional dependence of the mechanical properties. Our experiments confirm that human brain tissue is nonlinear and viscoelastic, with a pronounced compression-tension asymmetry. Using our measurements, we compare the performance of five common constitutive models, neo-Hookean, Mooney-Rivlin, Demiray, Gent, and Ogden, and show that only the isotropic modified one-term Ogden model is capable of representing the hyperelastic behavior under combined shear, compression, and tension loadings: with a shear modulus of 0.4-1.4kPa and a negative nonlinearity parameter it captures the compression-tension asymmetry and the increase in shear stress under superimposed

  1. [Japanese ethos and organ transplantation from brain-dead donors].

    Science.gov (United States)

    Akiba, Etsuko

    2010-12-01

    A trend observed since the 1980s in the Japanese academic scene is the overturning of Hippocratic ethics by American individualistic bioethics. However, the Japanese ethos is more sympathetic to personalistic bioethics rooted in Hippocratic ethics, which assumes the universal view of the 'interdependent self' clearly marked off from the 'independent self' specific to American culture. In Japan, organ transplantation from brain-dead donors is promoted despite the lack of consensus on whether brain death signifies death of the individual. From the viewpoint of personalistic bioethics, this situation is problematic because it violates the dictum primum non nocere of the Hippocratic Oath. We should therefore first establish consensus on brain death and then promote a 'culture of donation' based on human dignity.

  2. Effect of vitro preservation on mechanical properties of brain tissue

    Science.gov (United States)

    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.

  3. Matrix-Assisted Transplantation of Functional Beige Adipose Tissue.

    Science.gov (United States)

    Tharp, Kevin M; Jha, Amit K; Kraiczy, Judith; Yesian, Alexandra; Karateev, Grigory; Sinisi, Riccardo; Dubikovskaya, Elena A; Healy, Kevin E; Stahl, Andreas

    2015-11-01

    Novel, clinically relevant, approaches to shift energy balance are urgently needed to combat metabolic disorders such as obesity and diabetes. One promising approach has been the expansion of brown adipose tissues that express uncoupling protein (UCP) 1 and thus can uncouple mitochondrial respiration from ATP synthesis. While expansion of UCP1-expressing adipose depots may be achieved in rodents via genetic and pharmacological manipulations or the transplantation of brown fat depots, these methods are difficult to use for human clinical intervention. We present a novel cell scaffold technology optimized to establish functional brown fat-like depots in vivo. We adapted the biophysical properties of hyaluronic acid-based hydrogels to support the differentiation of white adipose tissue-derived multipotent stem cells (ADMSCs) into lipid-accumulating, UCP1-expressing beige adipose tissue. Subcutaneous implantation of ADMSCs within optimized hydrogels resulted in the establishment of distinct UCP1-expressing implants that successfully attracted host vasculature and persisted for several weeks. Importantly, implant recipients demonstrated elevated core body temperature during cold challenges, enhanced respiration rates, improved glucose homeostasis, and reduced weight gain, demonstrating the therapeutic merit of this highly translatable approach. This novel approach is the first truly clinically translatable system to unlock the therapeutic potential of brown fat-like tissue expansion. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  4. Methodological aspects of MRI of transplanted superparamagnetic iron oxide-labeled mesenchymal stem cells in live rat brain.

    Directory of Open Access Journals (Sweden)

    Daria Namestnikova

    Full Text Available In vivo tracking of transplanted mesenchymal stem cells (MSCs migration and homing is vital for understanding the mechanisms of beneficial effects of MSCs transplantation in animal models of diseases and in clinical trials. Transplanted cells can be labeled with superparamagnetic iron oxide (SPIO particles and visualized in vivo using a number of iron sensitive MRI techniques. However, the applicability of those techniques for SPIO-labeled MSCs tracking in live brain has not been sufficiently investigated. The goal of this study was to estimate the efficiency of various MRI techniques of SPIO-labeled cell tracing in the brain. To achieve that goal, the precision and specificity of T2WI, T2*WI and SWI (Susceptibility-Weighted Imaging techniques of SPIO-labeled MSCs tracing in vitro and in live rat brain were for the first time compared in the same experiment. We have shown that SWI presents the most sensitive pulse sequence for SPIO-labeled MSCs MR visualization. After intracerebral administration due to limitations caused by local micro-hemorrhages the visualization threshold was 102 cells, while after intra-arterial transplantation SWI permitted detection of several cells or even single cells. There is just one publication claiming detection of individual SPIO-labeled MSCs in live brain, while the other state much lower sensitivity, describe detection of different cell types or high resolution tracing of MSCs in other tissues. This study confirms the possibility of single cell tracing in live brain and outlines the necessary conditions. SWI is a method convenient for the detection of single SPIO labeled MSCs and small groups of SPIO labeled MSCs in brain tissue and can be appropriate for monitoring migration and homing of transplanted cells in basic and translational neuroscience.

  5. Methodological aspects of MRI of transplanted superparamagnetic iron oxide-labeled mesenchymal stem cells in live rat brain.

    Science.gov (United States)

    Namestnikova, Daria; Gubskiy, Ilya; Kholodenko, Irina; Melnikov, Pavel; Sukhinich, Kirill; Gabashvili, Anna; Vishnevskiy, Daniil; Soloveva, Anastasia; Abakumov, Maxim; Vakhrushev, Igor; Lupatov, Alexei; Chekhonin, Vladimir; Gubsky, Leonid; Yarygin, Konstantin

    2017-01-01

    In vivo tracking of transplanted mesenchymal stem cells (MSCs) migration and homing is vital for understanding the mechanisms of beneficial effects of MSCs transplantation in animal models of diseases and in clinical trials. Transplanted cells can be labeled with superparamagnetic iron oxide (SPIO) particles and visualized in vivo using a number of iron sensitive MRI techniques. However, the applicability of those techniques for SPIO-labeled MSCs tracking in live brain has not been sufficiently investigated. The goal of this study was to estimate the efficiency of various MRI techniques of SPIO-labeled cell tracing in the brain. To achieve that goal, the precision and specificity of T2WI, T2*WI and SWI (Susceptibility-Weighted Imaging) techniques of SPIO-labeled MSCs tracing in vitro and in live rat brain were for the first time compared in the same experiment. We have shown that SWI presents the most sensitive pulse sequence for SPIO-labeled MSCs MR visualization. After intracerebral administration due to limitations caused by local micro-hemorrhages the visualization threshold was 102 cells, while after intra-arterial transplantation SWI permitted detection of several cells or even single cells. There is just one publication claiming detection of individual SPIO-labeled MSCs in live brain, while the other state much lower sensitivity, describe detection of different cell types or high resolution tracing of MSCs in other tissues. This study confirms the possibility of single cell tracing in live brain and outlines the necessary conditions. SWI is a method convenient for the detection of single SPIO labeled MSCs and small groups of SPIO labeled MSCs in brain tissue and can be appropriate for monitoring migration and homing of transplanted cells in basic and translational neuroscience.

  6. Risk of transferring malignant cells with transplanted frozen-thawed ovarian tissue

    DEFF Research Database (Denmark)

    Dolmans, Marie-Madeleine; Luyckx, Valérie; Donnez, Jacques

    2013-01-01

    Ovarian tissue cryopreservation and transplantation is a real option to preserve and restore fertility in young cancer patients. However, there is a concern regarding the possible presence of malignant cells in the ovarian tissue, which could lead to recurrence of the primary disease after...... residual disease before ovarian tissue transplantation. Indeed, these pathologies, reviewed here in detail, are considered to be most at risk of ovarian metastasis....... reimplantation. A review of the existing literature was done to evaluate the risk of transplanting malignant cells in case of the main malignant indications for ovarian tissue cryopreservation. For ovarian tissue from patients with hematologic malignancies, it is of paramount importance to identify minimal...

  7. Physiological Function and Transplantation of Scaffold-Free and Vascularized Human Cardiac Muscle Tissue

    National Research Council Canada - National Science Library

    K. R. Stevens; K. L. Kreutziger; S. K. Dupras; F. S. Korte; M. Regnier; V. Muskheli; M. B. Nourse; K. Bendixen; H. Reinecke; C. E. Murry; William A. Catterall

    2009-01-01

    Success of human myocardial tissue engineering for cardiac repair has been limited by adverse effects of scaffold materials, necrosis at the tissue core, and poor survival after transplantation due to ischemie injury...

  8. Current Status and Future Development of Cell Transplantation Therapy for Periodontal Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Toshiyuki Yoshida

    2012-01-01

    Full Text Available It has been shown that stem cell transplantation can regenerate periodontal tissue, and several clinical trials involving transplantation of stem cells into human patients have already begun or are in preparation. However, stem cell transplantation therapy is a new technology, and the events following transplantation are poorly understood. Several studies have reported side effects and potential risks associated with stem cell transplantation therapy. To protect patients from such risks, governments have placed regulations on stem cell transplantation therapies. It is important for the clinicians to understand the relevant risks and governmental regulations. This paper describes the ongoing clinical studies, basic research, risks, and governmental controls related to stem cell transplantation therapy. Then, one clinical study is introduced as an example of a government-approved periodontal cell transplantation therapy.

  9. Do not resuscitate, brain death, and organ transplantation: Islamic perspective

    Science.gov (United States)

    Chamsi-Pasha, Hassan; Albar, Mohammed Ali

    2017-01-01

    Muslim patients and families are often reluctant to discuss and accept fatal diagnoses and prognoses. In many instances, aggressive therapy is requested by a patient's family, prolonging the life of the patient at all costs. Islamic law permits the withdrawal of futile treatment, including life support, from terminally ill patients allowing death to take its natural course. “Do not resuscitate” is permitted in Islamic law in certain situations. Debate continues about the certainty of brain death criteria within Islamic scholars. Although brain death is accepted as true death by the majority of Muslim scholars and medical organizations, the consensus in the Muslim world is not unanimous, and some scholars still accept death only by cardiopulmonary criteria. Organ transplantation has been accepted in Islamic countries (with some resistance from some jurists). Many fatwas (decrees) of Islamic Jurisprudence Councils have been issued and allowed organs to be donated from living competent adult donor; and from deceased (cadavers), provided that they have agreed to donate or their families have agreed to donate after their death (usually these are brain-dead cases). A clear and well-defined policy from the ministry of health regarding do not resuscitate, brain death, and other end-of-life issues is urgently needed for all hospitals and health providers in most (if not all) Muslim and Arab countries. PMID:28469984

  10. Viscoelastic parameter identification of human brain tissue.

    Science.gov (United States)

    Budday, S; Sommer, G; Holzapfel, G A; Steinmann, P; Kuhl, E

    2017-10-01

    Understanding the constitutive behavior of the human brain is critical to interpret the physical environment during neurodevelopment, neurosurgery, and neurodegeneration. A wide variety of constitutive models has been proposed to characterize the brain at different temporal and spatial scales. Yet, their model parameters are typically calibrated with a single loading mode and fail to predict the behavior under arbitrary loading conditions. Here we used a finite viscoelastic Ogden model with six material parameters-an elastic stiffness, two viscoelastic stiffnesses, a nonlinearity parameter, and two viscous time constants-to model the characteristic nonlinearity, conditioning, hysteresis and tension-compression asymmetry of the human brain. We calibrated the model under shear, shear relaxation, compression, compression relaxation, and tension for four different regions of the human brain, the cortex, basal ganglia, corona radiata, and corpus callosum. Strikingly, unconditioned gray matter with 0.36kPa and white matter with 0.35kPa were equally stiff, whereas conditioned gray matter with 0.52kPa was three times stiffer than white matter with 0.18kPa. While both unconditioned viscous time constants were larger in gray than in white matter, both conditioned constants were smaller. These rheological differences suggest a different porosity between both tissues and explain-at least in part-the ongoing controversy between reported stiffness differences in gray and white matter. Our unconditioned and conditioned parameter sets are readily available for finite element simulations with commercial software packages that feature Ogden type models at finite deformations. As such, our results have direct implications on improving the accuracy of human brain simulations in health and disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Differential expression of proteoglycans in tissue remodeling and lymphangiogenesis after experimental renal transplantation in rats.

    Science.gov (United States)

    Rienstra, Heleen; Katta, Kirankumar; Celie, Johanna W A M; van Goor, Harry; Navis, Gerjan; van den Born, Jacob; Hillebrands, Jan-Luuk

    2010-02-05

    Chronic transplant dysfunction explains the majority of late renal allograft loss and is accompanied by extensive tissue remodeling leading to transplant vasculopathy, glomerulosclerosis and interstitial fibrosis. Matrix proteoglycans mediate cell-cell and cell-matrix interactions and play key roles in tissue remodeling. The aim of this study was to characterize differential heparan sulfate proteoglycan and chondroitin sulfate proteoglycan expression in transplant vasculopathy, glomerulosclerosis and interstitial fibrosis in renal allografts with chronic transplant dysfunction. Renal allografts were transplanted in the Dark Agouti-to-Wistar Furth rat strain combination. Dark Agouti-to-Dark Agouti isografts and non-transplanted Dark Agouti kidneys served as controls. Allograft and isograft recipients were sacrificed 66 and 81 days (mean) after transplantation, respectively. Heparan sulfate proteoglycan (collXVIII, perlecan and agrin) and chondroitin sulfate proteoglycan (versican) expression, as well as CD31 and LYVE-1 (vascular and lymphatic endothelium, respectively) expression were (semi-) quantitatively analyzed using immunofluorescence. Arteries with transplant vasculopathy and sclerotic glomeruli in allografts displayed pronounced neo-expression of collXVIII and perlecan. In contrast, in interstitial fibrosis expression of the chondroitin sulfate proteoglycan versican dominated. In the cortical tubular basement membranes in both iso- and allografts, induction of collXVIII was detected. Allografts presented extensive lymphangiogenesis (pproteoglycans being expressed are tightly associated with tissue remodeling after renal transplantation. Therefore, proteoglycans might be potential targets for clinical intervention in renal chronic transplant dysfunction.

  12. Transplantation of human neural stem cells restores cognition in an immunodeficient rodent model of traumatic brain injury.

    Science.gov (United States)

    Haus, Daniel L; López-Velázquez, Luci; Gold, Eric M; Cunningham, Kelly M; Perez, Harvey; Anderson, Aileen J; Cummings, Brian J

    2016-07-01

    Traumatic brain injury (TBI) in humans can result in permanent tissue damage and has been linked to cognitive impairment that lasts years beyond the initial insult. Clinically effective treatment strategies have yet to be developed. Transplantation of human neural stem cells (hNSCs) has the potential to restore cognition lost due to injury, however, the vast majority of rodent TBI/hNSC studies to date have evaluated cognition only at early time points, typically cell transplantation. Additionally, human cell engraftment and long-term survival in rodent models of TBI has been difficult to achieve due to host immunorejection of the transplanted human cells, which confounds conclusions pertaining to transplant-mediated behavioral improvement. To overcome these shortfalls, we have developed a novel TBI xenotransplantation model that utilizes immunodeficient athymic nude (ATN) rats as the host recipient for the post-TBI transplantation of human embryonic stem cell (hESC) derived NSCs and have evaluated cognition in these animals at long-term (≥2months) time points post-injury. We report that immunodeficient ATN rats demonstrate hippocampal-dependent spatial memory deficits (Novel Place, Morris Water Maze), but not non-spatial (Novel Object) or emotional/anxiety-related (Elevated Plus Maze, Conditioned Taste Aversion) deficits, at 2-3months post-TBI, confirming that ATN rats recapitulate some of the cognitive deficits found in immunosufficient animal strains. Approximately 9-25% of transplanted hNSCs survived for at least 5months post-transplantation and differentiated into mature neurons (NeuN, 18-38%), astrocytes (GFAP, 13-16%), and oligodendrocytes (Olig2, 11-13%). Furthermore, while this model of TBI (cortical impact) targets primarily cortex and the underlying hippocampus and generates a large lesion cavity, hNSC transplantation facilitated cognitive recovery without affecting either lesion volume or total spared cortical or hippocampal tissue volume. Instead, we

  13. Transgenic reporter mice as tools for studies of transplantability and connectivity of dopamine neuron precursors in fetal tissue grafts.

    Science.gov (United States)

    Thompson, Lachlan H; Björklund, Anders

    2009-01-01

    Cell therapy for Parkinson's disease (PD) is based on the idea that new midbrain dopamine (mDA) neurons, implanted directly into the brain of the patient, can structurally and functionally replace those lost to the disease. Clinical trials have provided proof-of-principle that the grafted mDA neurons can survive and function after implantation in order to provide sustained improvement in motor function for some patients. Nonetheless, there are a number of issues limiting the application of this approach as mainstream therapy, including: the use of human fetal tissue as the only safe and reliable source of transplantable mDA neurons, and variability in the therapeutic outcome. Here we review recent progress in this area from investigations using rodent models of PD, paying particular attention to the use of transgenic reporter mice as tools for neural transplantation studies. Cell type-specific expression of reporter genes, such as green fluorescent protein, affords valuable technical advantages in transplantation experiments, such as the ability to selectively isolate specific cell fractions from mixed populations prior to grafting, and the unambiguous visualization of graft-derived dopamine neuron fiber patterns after transplantation. The results from these investigations have given new insights into the transplantability of mDA precursors as well as their connectivity after grafting and have interesting implications for the development of stem cell based approaches for the treatment of PD.

  14. Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach.

    Science.gov (United States)

    Nih, Lina R; Moshayedi, Pouria; Llorente, Irene L; Berg, Andrew R; Cinkornpumin, Jessica; Lowry, William E; Segura, Tatiana; Carmichael, S Thomas

    2017-02-01

    This article presents data related to the research article "Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain" (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016) [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA)-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs) after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1) Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2) the use of a design of Experiment (DOE) approach (M.W. 2 Weible and T. Chan-Ling, 2007) [2] to select multi-factorial experimental conditions, and (3) Inflammatory response and cell survival after transplantation.

  15. Root and periodontal tissue development after allogenic tooth transplantation between rat littermates.

    Science.gov (United States)

    Andou, K; Nakamura, M; Ina, Y; Sasaki, K; Sasano, Y

    2011-05-01

    The study was designed to investigate the development of roots and periodontal tissues after allogenic tooth transplantation between rat littermates by micro-computed tomography (micro-CT) and histology. The upper right second molars in 2-week-old rats were extracted and immediately transplanted into the upper right first molar socket of rat littermates under anesthesia. The upper left second molars in 2-week-old recipient rats were used as a control. The rats were fixed and tissues analyzed at 0, 4, 8, or 12 weeks after transplantation. Root development of seven rats in each group was analyzed quantitatively using micro-CT. Periodontal tissue formation was examined qualitatively by histologic methods. Roots developed after allogenic transplantation, but they were significantly shorter than control roots. The number of roots varied from one to four in transplanted teeth, while it was consistently four in control teeth. Periodontal tissue formation in transplanted teeth was equivalent to that of the control teeth. Allogenic transplantation between rat littermates permits root development and periodontal tissue formation. © 2010 John Wiley & Sons A/S.

  16. [Brain death and organ transplantation: ethical dilemmas for nursing?].

    Science.gov (United States)

    Windels-Buhr, D

    1997-06-01

    According to the WHO Program, nurses should be active in public health care as equal members of a multiprofessional team. This position requires competent professional action, which also implies moral competence, especially necessitated by the coming paradigmatic changes caused by shifts in the previous and current boundaries of the paradigm human being. One reason for this shift are the greater medical technical possibilities. The medical definition of brain death as the death of a human being per se is one example of the altered boundary and its consequences. Must future components of the nursing metaparadigm be changed because of this? To what extent is nursing ethically obligated to integrate changes in social values into its metaparadigm, ethics and objectives? The nursing metaparadigm, Henderson's definition of nursing, the ICN's Basic Code of Ethics, and the nursing model according to Roper, Logan & Tierney were used as the basis in the analysis of the subject matter and problems. Furthermore, philosophical viewpoints of Jonas & Harris will be included to clarify the deontological and teleological aspects of standard ethics. Finally, conclusions are drawn about the intra- and interprofessional ethical discourse about brain death and organ transplantation among nursing professionals.

  17. Legal termination of a pregnancy resulting from transplanted cryopreserved ovarian tissue due to cancer recurrence

    DEFF Research Database (Denmark)

    Ernst, Emil Hagen; Offersen, Birgitte Vrou; Andersen, Claus Yding

    2013-01-01

    To report on a woman who conceived naturally and had a normal intrauterine pregnancy following transplantation of frozen/thawed ovarian tissue but decided to have an early abortion due to recurrence of breast cancer.......To report on a woman who conceived naturally and had a normal intrauterine pregnancy following transplantation of frozen/thawed ovarian tissue but decided to have an early abortion due to recurrence of breast cancer....

  18. Effects of brain death on donor organ viability in transplantation

    NARCIS (Netherlands)

    Hoeven, Joost Alexander Boreas van der

    2005-01-01

    Organ transplantation has evolved from an experimental procedure in the 1950's and 60's to the therapy of choice for end-stage organ failure. The first solid organ to outgrow the experimental transplantation setting was the kidney. At that time the succesful transplant programs were those in which

  19. Intracerebral transplants of primary muscle cells: a potential 'platform' for transgene expression in the brain

    Science.gov (United States)

    Jiao, S.; Schultz, E.; Wolff, J. A.

    1992-01-01

    After the transplantation of rat primary muscle cells into the caudate or cortex of recipient rats, the muscle cells were able to persist for at least 6 months. Muscle cells transfected with expression plasmids prior to transplantation were able to express reporter genes in the brains for at least 2 months. These results suggest that muscle cells might be a useful 'platform' for transgene expression in the brain.

  20. Robotic multimodality stereotactic brain tissue identification: work in progress

    Science.gov (United States)

    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.

  1. The concept of brain death did not evolve to benefit organ transplants.

    Science.gov (United States)

    Machado, Calixto; Kerein, Julius; Ferrer, Yazmina; Portela, Liana; de la C García, Maria; Manero, José M

    2007-04-01

    Although it is commonly believed that the concept of brain death (BD) was developed to benefit organ transplants, it evolved independently. Transplantation owed its development to advances in surgery and immunosuppressive treatment; BD owed its origin to the development of intensive care. The first autotransplant was achieved in the early 1900s, when studies of increased intracranial pressure causing respiratory arrest with preserved heartbeat were reported. Between 1902 and 1950, the BD concept was supported by the discovery of EEG, Crile's definition of death, the use of EEG to demonstrate abolition of brain potentials after ischaemia, and Crafoord's statement that death was due to cessation of blood flow. Transplantation saw the first xenotransplant in humans and the first unsuccessful kidney transplant from a cadaver. In the 1950s, circulatory arrest in coma was identified by angiography, and the death of the nervous system and coma dépassé were described. Murray performed the first successful kidney transplant. In the 1960s, the BD concept and organ transplants were instantly linked when the first kidney transplant using a brain-dead donor was performed; Schwab proposed to use EEG in BD; the Harvard Committee report and the Sydney Declaration appeared; the first successful kidney, lung and pancreas transplants using cadaveric (not brain-dead) donors were achieved; Barnard performed the first human heart transplant. This historical review demonstrates that the BD concept and organ transplantation arose separately and advanced in parallel, and only began to progress together in the late 1960s. Therefore, the BD concept did not evolve to benefit transplantation.

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

    Science.gov (United States)

    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

  3. Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology.

    Science.gov (United States)

    Sopko, Nikolai A; Matsui, Hotaka; Lough, Denver M; Miller, Devin; Harris, Kelly; Kates, Max; Liu, Xiaopu; Billups, Kevin; Redett, Richard; Burnett, Arthur L; Brandacher, Gerald; Bivalacqua, Trinity J

    2017-04-01

    Penile transplantation is a potential treatment option for severe penile tissue loss. Models of human penile rejection are lacking. Evaluate effects of rejection and immunosuppression on cavernous tissue using a novel ex vivo mixed lymphocyte reaction (MLR) model. Cavernous tissue and peripheral blood mononuclear cells (PBMCs) from 10 patients undergoing penile prosthesis operations and PBMCs from a healthy volunteer were obtained. Ex vivo MLRs were prepared by culturing cavernous tissue for 48h in media alone, in media with autologous PBMCs, or in media with allogenic PBMCs to simulate control, autotransplant, and allogenic transplant conditions with or without 1μM cyclosporine A (CsA) or 20nM tacrolimus (FK506) treatment. Rejection was characterized by PBMC flow cytometry and gene expression transplant array. Cavernous tissues were evaluated by histomorphology and myography to assess contraction and relaxation. Data were analyzed using two-way analysis of variance and unpaired Student t test. Flow cytometry and tissue array demonstrated allogenic PBMC activation consistent with rejection. Rejection impaired cavernous tissue physiology and was associated with cellular infiltration and apoptosis. CsA prevented rejection but did not improve tissue relaxation. CsA treatment impaired relaxation in tissues cultured without PBMCs compared with media and FK506. Study limitations included the use of penile tissue with erectile dysfunction and lack of cross-matching data. This model could be used to investigate the effects of penile rejection and immunosuppression. Additional studies are needed to optimize immunosuppression to prevent rejection and maximize corporal tissue physiology. This report describes a novel ex vivo model of human penile transplantation rejection. Tissue rejection impaired erectile tissue physiology. This report suggests that cyclosporin A might hinder corporal physiology and that other immunosuppressant agents, such as FK506, might be better suited

  4. The donor advocacy team: a risk management program for living organ, tissue, and cell transplant donors.

    Science.gov (United States)

    Eguchi, Susumu; Soyama, Akihiko; Nagai, Kazuhiro; Miyazaki, Yasushi; Kurihara, Shintaro; Hidaka, Masaaki; Ono, Shinichiro; Adachi, Tomohiko; Natsuda, Koji; Hara, Takanobu; Fujita, Fumihiko; Kanetaka, Kengo; Takatsuki, Mistuhisa

    2017-08-01

    Although the incidence of living donor death is low in Japan, statistics show one living liver donor death in more than 7000 living liver transplants. Thus, medical transplant personnel must recognize that the death of a living organ or tissue transplant donor can occur and develop an appropriate risk management program. We describe how Nagasaki University Hospital established and implemented a Donor Advocacy Team (DAT) program: a risk management program for initiation in the event of serious, persistent, or fatal impairment of an organ, tissue, or cell transplantation from a living donor. The purposes of the DAT program are as follows: 1. To disclose official information without delay. 2. To provide physical and psychological care to the patient experiencing impairment and their family. 3. To provide psychological care to the medical staff in charge of the transplant. 4. To standardize the responses of the diagnosis and treatment department staff and other hospital staff. 5. To minimize the damage that the whole medical transplantation system may suffer and leverage the occurrence for improvement. To address (1) and (5), actions, such as reporting and responses to the government, mass media, transplant-related societies, and organ transplant networks, have been established to ensure implementation.

  5. Autogenous tooth transplantation: evaluation of pulp tissue regeneration.

    Science.gov (United States)

    Marques-Ferreira, Manuel; Rabaça-Botelho, Maria-Filomena; Carvalho, Lina; Oliveiros, Barbara; Palmeirão-Carrilho, Eunice-Virgínia

    2011-11-01

    The aim of this study was to assess the pulp survival that occur in transplants of autologous teeth, by comparing two surgical techniques: the conventional technique (autotransplantation for newly formed alveoli), and an alternative technique, (autotransplants for alveoli in the initial phase of healing). In each surgical techniques were applied, randomly, either saline solution or Emdogain®. The study group comprised 26 patents, in which 28 teeth were transplanted to recipient sockets prepared mechanically. Of the 28 teeth transplanted, 4 were intentional replants, and of the remainer, 11 had the apex closed and 13 open. The mean age at the time of transplantation was 22.34 ± 8.14 years (mean ± SD). The transplantation were performed by the same operator, with the informed consent of the patient and authorized by the ethical committee of the hospital. Clinical and radiological examinations were performed during 24 to 65 months (48 ± 12.96; MED ± SD), from 10 days, 1 month, 3 months, 6 months and annually to 5.6 years. Only two transplanted teeth were lost, due persistent apical periodontitis, and one transplanted patient with open apex missed the treatment. In the teeth with pulp, we needed to perform root canal therapy in 9. In the 73% of the teeth with closed apex, we needed to perform root canal treatment, with no statistically significant difference found among closed apex and root canal therapy (p=0.083). In only 8% of the teeth with open apex did we need to perform root canal treatment, with an association between open apex and root canal therapy (p=0.0002). The overall success rate was 98% with significant difference for losses (p=0.0001). Although not a frequent procedure, it was concluded that autotransplanted teeth, performed with appropriate surgical care had a good prognosis, and can render a very useful service to the patients.

  6. Brain Tumor Tropism of Transplanted Human Neural Stem Cells Is Induced by Vascular Endothelial Growth Factor

    Directory of Open Access Journals (Sweden)

    Nils Ole Schmidt

    2005-06-01

    Full Text Available The transplantation of neural stem cells (NSCs offers a new potential therapeutic approach as a cell-based delivery system for gene therapy in brain tumors. This is based on the unique capacity of NSCs to migrate throughout the brain and to target invading tumor cells. However, the signals controlling the targeted migration of transplanted NSCs are poorly defined. We analyzed the in vitro and in vivo effects of angiogenic growth factors and protein extracts from surgical specimens of brain tumor patients on NSC migration. Here, we demonstrate that vascular endothelial growth factor (VEGF is able to induce a long-range attraction of transplanted human NSCs from distant sites in the adult brain. Our results indicate that tumorupregulated VEGF and angiogenic-activated microvasculature are relevant guidance signals for NSC tropism toward brain tumors.

  7. Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach

    Directory of Open Access Journals (Sweden)

    Lina R. Nih

    2017-02-01

    Full Text Available This article presents data related to the research article “Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain” (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016 [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1 Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2 the use of a design of Experiment (DOE approach (M.W. 2 Weible and T. Chan-Ling, 2007 [2] to select multi-factorial experimental conditions, and (3 Inflammatory response and cell survival after transplantation.

  8. Transplanted bone marrow stromal cells protect neurovascular units and ameliorate brain damage in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    Ito, Masaki; Kuroda, Satoshi; Sugiyama, Taku; Maruichi, Katsuhiko; Kawabori, Masahito; Nakayama, Naoki; Houkin, Kiyohiro; Iwasaki, Yoshinobu

    2012-10-01

    This study was aimed to assess whether bone marrow stromal cells (BMSC) could ameliorate brain damage when transplanted into the brain of stroke-prone spontaneously hypertensive rats (SHR-SP). The BMSC or vehicle was stereotactically engrafted into the striatum of male SHR-SP at 8 weeks of age. Daily loading with 0.5% NaCl-containing water was started from 9 weeks. MRIs and histological analysis were performed at 11 and 12 weeks, respectively. Wistar-Kyoto rats were employed as the control. As a result, T2-weighted images demonstrated neither cerebral infarct nor intracerebral hemorrhage, but identified abnormal dilatation of the lateral ventricles in SHR-SP. HE staining demonstrated selective neuronal injury in their neocortices. Double fluorescence immunohistochemistry revealed that they had a decreased density of the collagen IV-positive microvessels and a decreased number of the microvessels with normal integrity between basement membrane and astrocyte end-feet. BMSC transplantation significantly ameliorated the ventricular dilatation and the breakdown of neurovascular integrity. These findings strongly suggest that long-lasting hypertension may primarily damage neurovascular integrity and neurons, leading to tissue atrophy and ventricular dilatation prior to the occurrence of cerebral stroke. The BMSC may ameliorate these damaging processes when directly transplanted into the brain, opening the possibility of prophylactic medicine to prevent microvascular and parenchymal-damaging processes in hypertensive patients at higher risk for cerebral stroke. © 2012 Japanese Society of Neuropathology.

  9. Experience of nurses in the process of donation of organs and tissues for transplant

    Directory of Open Access Journals (Sweden)

    Edvaldo Leal de Moraes

    2014-04-01

    Full Text Available OBJECTIVE: to investigate the meaning of the action of nurses in the donation process to maintain the viability of organs and tissues for transplantation.METHOD: this qualitative study with a social phenomenological approach was conducted through individual interviews with ten nurses of three Organ and Tissue Procurement Services of the city of São Paulo.RESULTS: the experience of the nurses in the donation process was represented by the categories: obstacles experienced in the donation process, and interventions performed. The meaning of the action to maintain the viability of organs and tissues for transplantation was described by the categories: to change paradigms, to humanize the donation process, to expand the donation, and to save lives.FINAL CONSIDERATIONS: knowledge of the experience of the nurses in this process is important for healthcare professionals who work in different realities, indicating strategies to optimize the procurement of organs and tissues for transplantation.

  10. Experience of nurses in the process of donation of organs and tissues for transplant.

    Science.gov (United States)

    de Moraes, Edvaldo Leal; dos Santos, Marcelo José; Merighi, Miriam Aparecida Barbosa; Massarollo, Maria Cristina Komatsu Braga

    2014-01-01

    to investigate the meaning of the action of nurses in the donation process to maintain the viability of organs and tissues for transplantation. this qualitative study with a social phenomenological approach was conducted through individual interviews with ten nurses of three Organ and Tissue Procurement Services of the city of São Paulo. the experience of the nurses in the donation process was represented by the categories: obstacles experienced in the donation process, and interventions performed. The meaning of the action to maintain the viability of organs and tissues for transplantation was described by the categories: to change paradigms, to humanize the donation process, to expand the donation, and to save lives. knowledge of the experience of the nurses in this process is important for healthcare professionals who work in different realities, indicating strategies to optimize the procurement of organs and tissues for transplantation.

  11. A family of hyperelastic models for human brain tissue

    Science.gov (United States)

    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.

  12. Survival of transplanted human neural stem cell line (ReNcell VM) into the rat brain with and without immunosuppression.

    Science.gov (United States)

    Hovakimyan, M; Müller, J; Wree, A; Ortinau, S; Rolfs, A; Schmitt, O

    2012-09-01

    Functional replacement of specific neuronal populations through transplantation of neural tissue represents an attractive therapeutic strategy for treating neurodegenerative disorders like Parkinson's disease (PD). Even though the brain is a partially immune privileged site, immunosuppression is still needed for the prevention of host immune response, and thus, xenograft rejection. Here, we investigated the fate of human ventral mesencephalon derived immortalized cell line ReNcell VM upon unilateral transplantation into the intact rat striatum with or without immunosuppression with cyclosporine A (CsA). The status of xenografted human ReNcell VM cells was analysed by immunohistochemistry/immunofluorescence 4 and 6weeks after transplantation. Four weeks after transplantation, ReNcell VM cells could be detected in both groups, although the number of survived cells was significantly higher in brains of immunosuppressed rats. In contrast, only 2 out of 6 brains grafted without immunosuppression revealed human ReNcell VM cells 6weeks post grafting, whereas a considerable number of human cells could still be found in all the brains of immunosuppressed rats. Immunohistochemical analysis of grafted cells showed almost no evidence of neuronal differentiation, but rather astroglial development. In summary, we have shown that the immunosuppression is needed for the survival of human VM derived progenitor cells in the rat striatum. CsA affected cell survival, but not differentiation capacity: in both groups, grafted either with or without immunosuppression, the ReNcell VM cells lacked neuronal phenotype and developed preferentially into astroglia. Copyright © 2012 Elsevier GmbH. All rights reserved.

  13. Follicle activation is a significant and immediate cause of follicle loss after ovarian tissue transplantation.

    Science.gov (United States)

    Gavish, Zohar; Spector, Itay; Peer, Gil; Schlatt, Stefan; Wistuba, Joachim; Roness, Hadassa; Meirow, Dror

    2017-11-03

    Extensive follicle loss has been demonstrated in ovarian grafts post transplantation, reducing their productivity and lifespan. Several mechanisms for this loss have been proposed, and this study aims to clarify when and how the massive follicle loss associated with transplantation of ovarian tissue graft occurs. An understanding of the mechanisms of follicle loss will pinpoint potential new targets for optimization and improvement of this important fertility preservation technique. Frozen-thawed marmoset (n = 15), bovine (n = 37), and human (n = 46) ovarian cortical tissue strips were transplanted subcutaneously into immunodeficient castrated male mice for 3 or 7 days. Histological (H&E, Masson's trichrome) analysis and immunostaining (Ki-67, GDF9, cleaved caspase-3) were conducted to assess transplantation-associated follicle dynamics, with untransplanted frozen-thawed tissue serving as a negative control. Evidence of extensive primordial follicle (PMF) activation and loss was observed already 3 days post transplantation in marmoset, bovine, and human tissue grafts, compared to frozen-thawed untransplanted controls (p < 0.001). No significant additional PMF loss was observed 7 days post transplantation. Recovered grafts of all species showed markedly higher rates of proliferative activity and progression from dormant to growing follicles (Ki-67 and GDF9 staining) as well as higher growing/primordial (GF/PMF) ratio (p < 0.02) and higher collagen levels compared with untransplanted controls. This multi-species study demonstrates that follicle activation plays an important role in transplantation-induced follicle loss, and that it occurs within a very short time frame after grafting. These results underline the need to prevent this activation at the time of transplantation in order to retain the maximal possible follicle reserve and extend graft lifespan.

  14. Allogeneic corneoscleral limbus tissue transplantation for treatment of the necrosis in porphyria eye disease

    Directory of Open Access Journals (Sweden)

    Feng Yan

    2014-08-01

    Full Text Available Porphyria cutanea tarda (PCT with ocular complications are rarely reported. To the best of our knowledge, no reports exist on allogeneic corneoscleral limbus tissue transplantation for treatment of these. Amniotic membrane grafting had been performed in their patient suffering from porphyria eye disease, but necrosis developed in the grafts. Nevertheless, in our patient, allogeneic corneoscleral limbus transplantation prevented necrosis from development at corneoscleral limbus. So we considered that the allogeneic corneoscleral limbus transplantation might be an option to repair the necrosis in porphyria eye disease with avoiding sunlight and using artificial tear drops.

  15. The mouse cornea as a transplantation site for live imaging of engineered tissue constructs.

    Science.gov (United States)

    Poché, Ross A; Saik, Jennifer E; West, Jennifer L; Dickinson, Mary E

    2010-04-01

    The field of tissue engineering aims to recapitulate healthy human organs and 3-D tissue structures in vitro and then transplant these constructs in vivo where they can be effectively integrated within the recipient patient and become perfused by the host circulation. To improve the design of materials for artificial tissue scaffolds, it would be ideal to have a high-throughput imaging system that allows one to directly monitor transplanted tissue constructs in live animals over an extended period of time. By combining such an assay with transgenic, cell-specific fluorescent reporters, one could monitor such parameters as tissue construct perfusion, donor cell survival, and donor-host cell interaction/integration. Here, we describe a protocol for a modified version of the classical corneal micropocket angiogenesis assay, employing it as a live imaging "window" to monitor angiogenic poly(ethylene glycol) (PEG)-based hydrogel tissue constructs.

  16. Alteration of Brain Oxygenation During "Piggy Back" Liver Transplantation

    Science.gov (United States)

    Panzera, Piercarmine; Greco, Luigi; Carravetta, Giuseppe; Gentile, Antonella; Catalano, Giorgio; Cicco, Giuseppe; Memeo, Vincenzo

    Relevant changes in cerebral circulation occur during "Piggy Back" liver transplantation. Particularly at the washout-reperfusion time the cerebral perfusion suddenly changes from its lowest to its highest values. Further investigation is required to evaluate whether patients with the greatest change in cerebral oxygenation at this time point will suffer neurological complications after transplantation.

  17. SUITABILITY OF CORNEAL TISSUE FOR TRANSPLANTATION PROCURED FROM HANGING CASES

    Directory of Open Access Journals (Sweden)

    Rekha Gyanchand

    2017-06-01

    Full Text Available BACKGROUND Requirement of donor cornea is essential to target the corneal blind. The best method to procure such corneas is from any major hospitals, which has a mortuary facility. The eye donation with hanging as the cause of death is very common in a mortuary setup. Some factors that are concerning regarding corneas procured from death due to hanging is the prolonged exposure of the cornea at the time of death, the exact time of death is not known, most of the cadavers are refrigerated for investigations as these arrive at the mortuary usually at night. Due to these reasons, the corneal surgeons are hesitant to use corneas procured from death due to hanging for corneal transplantation. Analysing these corneas would contribute to a great extent to the donor cornea pool in providing sight to the corneal blind, especially as majority are young individuals who commit suicide by hanging. In this study, the donor corneas were analysed with regards to corneal epithelial defect, endothelial cell morphology and utilisation of these corneas for transplantation. The aim of the HCRP study is to analyse the effect of death due to hanging on donor cornea. 1. Corneal epithelial status. 2. Corneal endothelial cell morphology. 3. Utilisation of corneas for transplantation. MATERIALS AND METHODS Donor corneas from 22 donors who died due to hanging were procured from hospital mortuary. All the 44 corneas were transplanted. Various parameters like demography, death to enucleation time, cadaver preservation in cold storage, endothelial cell density and utilisation of cornea for transplantation were noted. Design- Retrospective study. Statistical Analysis- Descriptive statistics, Pearson and Spearman correlation and Chi-square test were used to test the hypotheses. RESULTS Out of the 44 corneas analysed, 75% of the donors were refrigerated as a part of medicolegal investigations protocol. The average DTP time was 12 hours in refrigerated group and 5 hours in non

  18. Neural Stem Cell Transplantation Promotes Functional Recovery from Traumatic Brain Injury via Brain Derived Neurotrophic Factor-Mediated Neuroplasticity.

    Science.gov (United States)

    Xiong, Liu-Lin; Hu, Yue; Zhang, Piao; Zhang, Zhuo; Li, Li-Hong; Gao, Guo-Dong; Zhou, Xin-Fu; Wang, Ting-Hua

    2017-04-18

    Traumatic brain injury (TBI) induces cognitive impairments, motor and behavioral deficits. Previous evidences have suggested that neural stem cell (NSC) transplantation could facilitate functional recovery from brain insults, but their underlying mechanisms remains to be elucidated. Here, we established TBI model by an electromagnetic-controlled cortical impact device in the rats. Then, 5 μl NSCs (5.0 × 10 5 /μl), derived from green fluorescent protein (GFP) transgenic mouse, was transplanted into the traumatic brain regions of rats at 24 h after injury. After differentiation of the NSCs was determined using immunohistochemistry, neurological severity scores (NSS) and rotarod test were conducted to detect the neurological behavior. Western blot and RT-PCR as well as ELASA were used to evaluate the expression of synaptophysin and brain-derived neurotrophic factor (BDNF). In order to elucidate the role of BDNF on the neural recovery after NSC transplantation, BDNF knockdown in NSC was performed and transplanted into the rats with TBI, and potential mechanism for BDNF knockdown in the NSC was analyzed using microassay analysis. Meanwhile, BDNF antibody blockade was conducted to further confirm the effect of BDNF on neural activity. As a result, an increasing neurological function improvement was seen in NSC transplanted rats, which was associated with the upregulation of synaptophysin and BDNF expression. Moreover, transplantation of BDNF knockdown NSCs and BDNF antibody block reduced not only the level of synaptophysin but also exacerbated neurological function deficits. Microassay analysis showed that 14 genes such as Wnt and Gsk3-β were downregulated after BDNF knockdown. The present data therefore showed that BDNF-mediated neuroplasticity underlie the mechanism of NSC transplantation for the treatment of TBI in adult rats.

  19. Transplantation of embryonic porcine neocortical tissue into newborn rats

    DEFF Research Database (Denmark)

    Castro, Anthony J; Meyer, Morten; Møller Dall, Annette

    2003-01-01

    Several previous studies, suggesting the potential use of embryonic xenografts in the treatment of neurological disorders, indicate that neural growth and axonal guidance factors may function across species. In this light, blocks of fetal porcine neocortex were grafted into small cortical lesion...... with cyclosporin A did not appear to promote graft survival. Some transplants grew to extremely large proportions and were characterized by bands of cells and bundles of axons as observed using immunohistochemical staining for pig neurofilament. Neurofilament-positive axons projected from several of the grafts...... to course through the corpus callosum to the contralateral cortex or to course ipsilaterally within the subcortical white matter, where labeled fibers could be traced to the midbrain crus cerebri in older transplants. Bundles of axons were also observed coursing within the ipsilateral caudate putamen where...

  20. Measuring thrombin activity in frozen brain tissue.

    Science.gov (United States)

    Reuveni, Gilad; Golderman, Valery; Shavit-Stein, Efrat; Rosman, Yossi; Shrot, Shai; Chapman, Joab; Harnof, Sagi

    2017-12-06

    Thrombin is a coagulation factor implicated in various pathological and physiological processes in the brain, exerting beneficial and deleterious effects in a concentration-dependent manner. Measurement of thrombin activity levels in pathological animal models is needed and in some cases, because of technical considerations, only frozen samples are available. In the current study, we used a quantitative method to evaluate thrombin activity in fresh and frozen brain sections of 43 male and female adult healthy mice. We stratified data per brain section, brain hemisphere, and mouse sex. We found lower thrombin activity in frozen sections compared with fresh sections, falling within levels considered central nervous system protective in previous studies. The results suggest that fresh section thrombin activity levels in healthy mice can be extrapolated from frozen brain sections. In addition, we found varying thrombin activity across the brain sections, with maximal activity in the olfactory system and hippocampus-containing sections. Thrombin activity did not vary between males and females, or between the right and the left hemispheres, in a statistically significantly manner.

  1. Chemical Probes for Visualizing Intact Animal and Human Brain Tissue.

    Science.gov (United States)

    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.

  2. Autologous subcutaneous adipose tissue transplants improve adipose tissue metabolism and reduce insulin resistance and fatty liver in diet?induced obesity rats

    OpenAIRE

    Torres?Villalobos, Gonzalo; Hamdan?P?rez, Nashla; D?az?Villase?or, Andrea; Tovar, Armando R.; Torre?Villalvazo, Ivan; Ordaz?Nava, Guillermo; Mor?n?Ramos, Sof?a; Noriega, Lilia G.; Mart?nez?Ben?tez, Braulio; L?pez?Garibay, Alejandro; Torres?Landa, Samuel; Ceballos?Cant?, Juan C.; Tovar?Palacio, Claudia; Figueroa?Ju?rez, Elizabeth; Hiriart, Marcia

    2016-01-01

    Abstract Long?term dietary and pharmacological treatments for obesity have been questioned, particularly in individuals with severe obesity, so a new approach may involve adipose tissue transplants, particularly autologous transplants. Thus, the aim of this study was to evaluate the metabolic effects of autologous subcutaneous adipose tissue (SAT) transplants into two specific intraabdominal cavity sites (omental and retroperitoneal) after 90?days. The study was performed using two different ...

  3. Evidence of the Association Between Psychology and Tissue and Organ Transplantation in Brazil.

    Science.gov (United States)

    Silva, J D A; Ariente, L C; Roza, B A; Mucci, S

    2016-09-01

    The addition of psychologists to organ transplant teams is still new in Brazil. In seeking the efficient performance of this professional, the knowledge of the scientific production and the development of research in the area is fundamental. In this sense, this study aims to survey the Brazilian scientific research that has investigated the psychologic aspects involved in tissue and organ transplantation. A literature narrative review was performed with the use of the "Transplante AND Psicologia" descriptors in the Biblioteca Virtual em Saúde and the CAPES Journal Portal. Fifty-three articles were found, of which 22 met the inclusion criteria: publications dating from 2000 to 2014 and the main topic of interest of the studies being quality of life, followed by organ donation. The instruments used most frequently were interviews developed by the researchers and the SF-36 Quality of Life Questionnaire. Recent Brazilian studies on the association between psychology and transplantation are still scarce, possibly because of the recent addition of psychologists to transplantation teams. Therefore, it is suggested that more scientific research is made in the area and that the objects of study are more varied, to ensure adequacy of the psychologist to meet the specific demands of organ and tissue transplantation process. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Liver Transplantation in the Mouse: Insights Into Liver Immunobiology, Tissue Injury and Allograft Tolerance

    Science.gov (United States)

    Yokota, Shinichiro; Yoshida, Osamu; Ono, Yoshihiro; Geller, David A.; Thomson, Angus W.

    2016-01-01

    The surgically-demanding mouse orthotopic liver transplant model was first described in 1991. It has proved a powerful research tool for investigation of liver biology, tissue injury, the regulation of alloimmunity and tolerance induction and the pathogenesis of specific liver diseases. Liver transplantation in mice has unique advantages over transplantation of the liver in larger species, such as the rat or pig, since the mouse genome is well-characterized and there is much greater availability of both genetically-modified animals and research reagents. Liver transplant experiments using various transgenic or gene knockout mice has provided valuable mechanistic insights into the immuno- and pathobiology of the liver and the regulation of graft rejection and tolerance over the past 25 years. The molecular pathways identified in regulation of tissue injury and promotion of liver transplant tolerance provide new potential targets for therapeutic intervention to control adverse inflammatory responses/ immune-mediated events in the hepatic environment and systemically. Conclusion: Orthotopic liver transplantation in the mouse is a valuable model for gaining improved insights into liver biology, immunopathology and allograft tolerance that may result in therapeutic innovation in liver and other diseases. PMID:26709949

  5. Verification of cell viability in bioengineered tissues and organs before clinical transplantation.

    Science.gov (United States)

    Jungebluth, Philipp; Haag, Johannes C; Lim, Mei L; Lemon, Greg; Sjöqvist, Sebastian; Gustafsson, Ylva; Ajalloueian, Fatemeh; Gilevich, Irina; Simonson, Oscar E; Grinnemo, Karl H; Corbascio, Matthias; Baiguera, Silvia; Del Gaudio, Costantino; Strömblad, Staffan; Macchiarini, Paolo

    2013-05-01

    The clinical outcome of transplantations of bioartificial tissues and organs depends on the presence of living cells. There are still no standard operative protocols that are simple, fast and reliable for confirming the presence of viable cells on bioartificial scaffolds prior to transplantation. By using mathematical modeling, we have developed a colorimetric-based system (colorimetric scale bar) to predict the cell viability and density for sufficient surface coverage. First, we refined a method which can provide information about cell viability and numbers in an in vitro setting: i) immunohistological staining by Phalloidin/DAPI and ii) a modified colorimetric cell viability assay. These laboratory-based methods and the developed colorimetric-based system were then validated in rat transplantation studies of unseeded and seeded tracheal grafts. This was done to provide critical information on whether the graft would be suitable for transplantation or if additional cell seeding was necessary. The potential clinical impact of the colorimetric scale bar was confirmed using patient samples. In conclusion, we have developed a robust, fast and reproducible colorimetric tool that can verify and warrant viability and integrity of an engineered tissue/organ prior to transplantation. This should facilitate a successful transplantation outcome and ensure patient safety. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Facilitated assessment of tissue loss following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Anders eHånell

    2012-03-01

    Full Text Available All experimental models of traumatic brain injury (TBI result in a progressive loss of brain tissue. The extent of tissue loss reflects the injury severity and can be measured to evaluate the potential neuroprotective effect of experimental treatments. Quantitation of tissue volumes is commonly performed using evenly spaced brain sections stained using routine histochemical methods and digitally captured. The brain tissue areas are then measured and the corresponding volumes are calculated using the distance between the sections. Measurements of areas are usually performed using a general purpose image analysis software and the results are then transferred to another program for volume calculations. To facilitate the measurement of brain tissue loss we developed novel algorithms which automatically separate the areas of brain tissue from the surrounding image background and identify the ventricles. We implemented these new algorithms by creating a new computer program (SectionToVolume which also has functions for image organization, image adjustments and volume calculations. We analyzed brain sections from mice subjected to severe focal TBI using both SectionToVolume and ImageJ, a commonly used image analysis program. The volume measurements made by the two programs were highly correlated and analysis using SectionToVolume required considerably less time. The inter-rater reliability was high. Given the extensive use of brain tissue loss measurements in TBI research, SectionToVolume will likely be a useful tool for TBI research. We therefore provide both the source code and the program as attachments to this article.

  7. Brain-gut-adipose-tissue communication pathways at a glance.

    Science.gov (United States)

    Yi, Chun-Xia; Tschöp, Matthias H

    2012-09-01

    One of the 'side effects' of our modern lifestyle is a range of metabolic diseases: the incidence of obesity, type 2 diabetes and associated cardiovascular diseases has grown to pandemic proportions. This increase, which shows no sign of reversing course, has occurred despite education and new treatment options, and is largely due to a lack of knowledge about the precise pathology and etiology of metabolic disorders. Accumulating evidence suggests that the communication pathways linking the brain, gut and adipose tissue might be promising intervention points for metabolic disorders. To maintain energy homeostasis, the brain must tightly monitor the peripheral energy state. This monitoring is also extremely important for the brain's survival, because the brain does not store energy but depends solely on a continuous supply of nutrients from the general circulation. Two major groups of metabolic inputs inform the brain about the peripheral energy state: short-term signals produced by the gut system and long-term signals produced by adipose tissue. After central integration of these inputs, the brain generates neuronal and hormonal outputs to balance energy intake with expenditure. Miscommunication between the gut, brain and adipose tissue, or the degradation of input signals once inside the brain, lead to the brain misunderstanding the peripheral energy state. Under certain circumstances, the brain responds to this miscommunication by increasing energy intake and production, eventually causing metabolic disorders. This poster article overviews current knowledge about communication pathways between the brain, gut and adipose tissue, and discusses potential research directions that might lead to a better understanding of the mechanisms underlying metabolic disorders.

  8. The effect of Setarud (IMODTM) on angiogenesis in transplanted human ovarian tissue to nude mice

    Science.gov (United States)

    Hormozi, Maryam; Talebi, Saeed; Khorram Khorshid, Hamid Reza; Zarnani, Amir-Hassan; Kamali, Koorosh; Jeddi-Tehrani, Mahmood; Soltangoraee, Haleh; Akhondi, Mohammad Mehdi

    2015-01-01

    Background: One of the promising methods in fertility preservation among women with cancer is cryopreservation of ovarian cortex but there are many drawbacks such as apoptosis and considerable reduction of follicular density in the transplanted ovary. One solution to reduce ischemic damage is enhancing angiogenesis after transplantation of ovarian cortex tissue. Objective: The aim of this study was to investigate the effect of Setarud, on angiogenesis in transplanted human ovarian tissue. Materials and Methods: In this case control study, twenty four nude mice were implanted subcutaneously, with human ovarian tissues, from four women. The mice were randomly divided into two groups (n=12): the experimental group was treated with Setarud, while control group received only vehicle. Each group was divided into three subgroups (n=4) based on the graft recovery days post transplantation (PT). The transplanted fragments were removed on days 2, 7, and 30 PT and the expression of Angiopoietin-1, Angiopoietin-2, and Vascular endothelial growth factor at both gene and protein levels and vascular density were studied in the grafted ovarian tissues. Results: On the 2nd and 7th day PT, the level of Angiopoietin-1 gene expression in case group was significantly lower than that in control group, while the opposite results were obtained for Angiopoietin-2 and Vascular endothelial growth factor. These results were also confirmed at the protein level. The density of vessels in Setarud group elevated significantly on day 7 PT compared to pre-treatment state. Conclusion: Our results showed that administration of Setarud may stimulates angiogenesis in transplanted human ovarian tissues, although further researches are needed before a clear judgment is made. PMID:26644788

  9. Pesticide residues in brain tissues of dairy cattle in Lembang

    Directory of Open Access Journals (Sweden)

    Indraningsih

    2006-03-01

    Full Text Available The use of pesticides to control plant diseases may cause residual formation in crops, its byproduct and environmental. Furthermore, the use of agriculture byproduct as animal feed may cause poisoning or residual formation in animal products. The purpose of this study is to investigate of pesticide residues in brain tissues of dairy cattle in relation to animal feed as a contamination source. Samples consisted of animal feeds (19 samples of fodder and 6 samples of feed, 31 samples of sera and 25 samples of brain tissues of dairy cattle collected from Lembang, West Java. Feeds and fodders were collected from dairy farms located in Lembang. Sera were directly collected from 31 heads of Frisien Holstein (FH cattle from the same location, while brain tissues of FH cattle were collected from a local animal slaughtering house. Pesticide residues were analysed using gas chromatography (GC. Both residues of organochlorines and organophosphates were detected from brain tissues with average residue concentration OP was 22.7 ppb and OC was 5.1 ppb and a total residue was 27.8 ppb. The pesticide residues in brain tissues are new information that should be taken into consideration since the Indonesian consumed this tissues as an oval. Although pesticides residue concentration was low, pathological changes were noted microscopically from the brain tissues including extracellular vacuolisation, focal necrosis, haemorrhages, dilatation of basement membrane without cellular infiltration. Both pesticide residues were also detected in sera, where OP (9.0 ppb was higher than OC (4.9 ppb. These pesticides were also detected in animal feeds consisting fodders and feeds. Residues of OP (12.0 ppb were higher than OC (1.8 ppb in feeds, but residues of OP (16.8 ppb were lower than OC (18.7 ppb in fodders. Although, pesticide residues in sera and brain tissues were below the maximum residue limits (MRL of fat, the presence of pesticides in brain tissues should be taken

  10. The role of allofibroblasts transplantation in cartilaginous tissue regeneration process

    OpenAIRE

    Khadjibaev Аbdukhakim Muminovich; Tilyakov Akbar Buriyevich; Magrupov Bokhodir Asadullaevich; Urazmetova Maisa Dmitriyevna; Ubaydullaev Bobur Sabirovich

    2017-01-01

    Aim of investigation. Ground of embryonal allofibroblasts in the process of cartilaginous tissue regeneration. Material and methods. Investigation is based on the study the results of stimulation cartilaginous tissue regeneration process in the conditions of embryonal allofibroblasts application in 24 experimental sexually mature rabbits in which the model of symphysis pubis rupture with its following recovery have been used. Pieces of cartilaginous tissue have been fixed in 10% neutral forma...

  11. Which Donor for Uterus Transplants: Brain-Dead Donor or Living Donor? A Systematic Review.

    Science.gov (United States)

    Lavoué, Vincent; Vigneau, Cécile; Duros, Solène; Boudjema, Karim; Levêque, Jean; Piver, Pascal; Aubard, Yves; Gauthier, Tristan

    2017-02-01

    The aim of this systematic review was to evaluate and compare the pros and cons of using living donors or brain-dead donors in uterus transplantation programs, 2 years after the first worldwide live birth after uterus transplantation. The Medline database and the Central Cochrane Library were used to locate uterine transplantation studies carried out in human or nonhuman primates. All types of articles (case reports, original studies, meta-analyses, reviews) in English or French were considered for inclusion. Overall, 92 articles were screened and 44 were retained for review. Proof of concept for human uterine transplantation was demonstrated in 2014 with a living donor. Compared with a brain-dead donor strategy, a living donor strategy offers greater possibilities for planning surgery and also decreases cold ischemia time, potentially translating into a higher success rate. However, this approach poses ethical problems, given that the donor is exposed to surgery risks but does not derive any direct benefit. A brain-dead donor strategy is more acceptable from an ethical viewpoint, but its feasibility is currently unproven, potentially owing to a lack of compatible donors, and is associated with a longer cold ischemia time and a potentially higher rejection rate. The systematic review demonstrates that uterine transplantation is a major surgical innovation for the treatment of absolute uterine factor infertility. Living and brain-dead donor strategies are not mutually exclusive and, in view of the current scarcity of uterine grafts and the anticipated future rise in demand, both will probably be necessary.

  12. Regeneration of Cartilaginous Tissue After Transplantation of Allofibroblasts

    Directory of Open Access Journals (Sweden)

    A. B. Tilyakov

    2016-01-01

    Full Text Available Aim of investigation. To prove the usefulness of the use of embryonic fibroblasts for the regeneration of cartilaginous tissue.Material and methods. New experimental model of symphysis pubis rupture followed by its recovery was employed in 24 male Shinshilla rabbits (2.3—3.5 kg body mass in 3 series of experiments. In the first series, reconstruction was not employed. In the 2nd series, the reconstruction of symphisis was performed with the aid of tantal wired cerclage (d=1.2 mm. In the 3d series, the reconstitution was the same as in the previous series of experiments with addition of grown embrional allofibroblast tissue pieces. Duration of experiments was 7, 14, 21and 30 days. After each experiment, pieces of cartilaginous tissue were fixed with 10% neutral formalin and embedded in paraffin. Histological sections were stained with hematoxylin, eosin and VanGieson. Results. After the rupture of symphysis pubis of the pelvic bone, the cartilaginous tissue undergone alterations followed by formation of chondromatous nodules of different sizes and sclerosis of surrounding muscular and osseous tissues. In the second series of experiment after pelvis symphysis pubis rupture and symphysis recovery with the help of cerclage, the morphologic investigation revealed the formation of mixed initial callus consisting of connective and chondromatous tissue elements. In the third series of experiment it has been shown that within 4 weeks of experiment, the connective tissue with intensive basophil stain is formed in the area of symphysis pubisrupture. Connective tissue formation in surrounding soft tissue structures was associated with the formation of cartilaginous cells.Conclusion. Process of formation of cartilaginous tissue in the area of symphysis pubis rupture as evident by the experimental observation demonstrates the stimulating influence of allogeneic fibroblasts on process of cartilaginous tissue regeneration that ensures premises for

  13. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    Science.gov (United States)

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-07-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

  14. Digital tissue and what it may reveal about the brain.

    Science.gov (United States)

    Morgan, Josh L; Lichtman, Jeff W

    2017-10-30

    Imaging as a means of scientific data storage has evolved rapidly over the past century from hand drawings, to photography, to digital images. Only recently can sufficiently large datasets be acquired, stored, and processed such that tissue digitization can actually reveal more than direct observation of tissue. One field where this transformation is occurring is connectomics: the mapping of neural connections in large volumes of digitized brain tissue.

  15. Measurement of Steroid Concentrations in Brain Tissue: Methodological Considerations

    Science.gov (United States)

    Taves, Matthew D.; Ma, Chunqi; Heimovics, Sarah A.; Saldanha, Colin J.; Soma, Kiran K.

    2011-01-01

    It is well recognized that steroids are synthesized de novo in the brain (neurosteroids). In addition, steroids circulating in the blood enter the brain. Steroids play numerous roles in the brain, such as influencing neural development, adult neuroplasticity, behavior, neuroinflammation, and neurodegenerative diseases such as Alzheimer’s disease. In order to understand the regulation and functions of steroids in the brain, it is important to directly measure steroid concentrations in brain tissue. In this brief review, we discuss methods for the detection and quantification of steroids in the brain. We concisely present the major advantages and disadvantages of different technical approaches at various experimental stages: euthanasia, tissue collection, steroid extraction, steroid separation, and steroid measurement. We discuss, among other topics, the potential effects of anesthesia and saline perfusion prior to tissue collection; microdissection via Palkovits punch; solid phase extraction; chromatographic separation of steroids; and immunoassays and mass spectrometry for steroid quantification, particularly the use of mass spectrometry for “steroid profiling.” Finally, we discuss the interpretation of local steroid concentrations, such as comparing steroid levels in brain tissue with those in the circulation (plasma vs. whole blood samples; total vs. free steroid levels). We also present reference values for a variety of steroids in different brain regions of adult rats. This brief review highlights some of the major methodological considerations at multiple experimental stages and provides a broad framework for designing studies that examine local steroid levels in the brain as well as other steroidogenic tissues, such as thymus, breast, and prostate. PMID:22654806

  16. FORUM Human tissue and organ transplant provisions: Chapter 8 of ...

    African Journals Online (AJOL)

    permanent residents; (iii) donations of human bodies and tissue of deceased persons; (iv) consent to donations of human tissue on behalf of deceased persons; (v) allocation and use of human organs of ... It is also an offence to sell or trade.

  17. Targeting of Deep Brain Structures with Microinjections for Delivery of Drugs, Viral Vectors, or Cell Transplants

    Science.gov (United States)

    Gonzalez-Perez, Oscar; Guerrero-Cazares, Hugo; Quiñones-Hinojosa, Alfredo

    2010-01-01

    Microinjections into the brain parenchyma are important procedures to deliver drugs, viral vectors or cell transplants. The brain lesion that an injecting needle produces during its trajectory is a major concern especially in the mouse brain for not only the brain is small but also sometimes multiple injections are needed. We show here a method to produce glass capillary needles with a 50-μm lumen which significantly reduces the brain damage and allows a precise targeting into the rodent brain. This method allows a delivery of small volumes (from 20 to 100 nl), reduces bleeding risks, and minimizes passive diffusion of drugs into the brain parenchyma. By using different size of capillary glass tubes, or changing the needle lumen, several types of substances and cells can be injected. Microinjections with a glass capillary tube represent a significant improvement in injection techniques and deep brain targeting with minimal collateral damage in small rodents. PMID:21178958

  18. Optimizing outcomes from ovarian tissue cryopreservation and transplantation; activation versus preservation

    DEFF Research Database (Denmark)

    Meirow, Dror; Roness, Hadassa; Kristensen, Stine Gry

    2015-01-01

    Ovarian tissue cryopreservation and transplantation (OTCP) is gaining increasing traction in the field of fertility preservation as a result of accumulated successes. We now have a decade of experience with the technique, with tens of live births and greater than 90% return of ovarian function...

  19. West Nile Virus RNA in Tissues from Donor Associated with Transmission to Organ Transplant Recipients

    Centers for Disease Control (CDC) Podcasts

    2013-11-19

    William Hale reads an abridged version of the Emerging Infectious Diseases’ dispatch, West Nile Virus RNA in Tissues from Donor Associated with Transmission to Organ Transplant Recipients.  Created: 11/19/2013 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/21/2013.

  20. Alterações fisiológicas da morte encefálica em potenciais doadores de órgãos e tecidos para transplantes Los cambios fisiológicos de la muerte cerebral en potenciales donadores de órganos y tejidos para trasplante Physiological changes of brain death in potential donors of organs and tissues for transplantation

    OpenAIRE

    Sarah Gabriel Freire; Izaura Luzia Silvério Freire; Juliana Teixeira Jales Menescal Pinto; Quinidia Lúcia Duarte de Almeida Quithé de Vasconcelos; Gilson de Vasconcelos Torres

    2012-01-01

    Objetivou-se descrever as alterações fisiológicas da morte encefálica em potenciais doadores de órgãos e tecidos para transplantes. Estudo exploratório descritivo com dados prospectivos e abordagem quantitativa realizado nas unidades de emergência e terapia intensiva adulto de um hospital de Pernambuco no período de abril a outubro de 2011. A população constou de 32 potenciais doadores de órgãos e tecidos para transplantes. Após aprovação do Comitê de Ética em Pesquisa, os dados foram coletad...

  1. Combined transplantation of mesenchymal stem cells and endothelial progenitor cells for tissue engineering: a systematic review and meta-analysis.

    Science.gov (United States)

    Sun, Kunming; Zhou, Zheng; Ju, Xinxin; Zhou, Yang; Lan, Jiaojiao; Chen, Dongdong; Chen, Hongzhi; Liu, Manli; Pang, Lijuan

    2016-10-10

    Combined cell implantation has been widely applied in tissue engineering in recent years. In this meta-analysis, we aimed to establish whether the combined transplantation of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) promotes angiogenesis and tissue repair, compared with transplantation of a single cell type, following tissue injury or during tissue regeneration. The electronic databases PubMed, EMBASE, MEDLINE, Chinese Biomedical Literature, and China National Knowledge Infrastructure were searched in this systematic review and meta-analysis. Eighteen controlled preclinical studies involving MSC and EPC transplantation in animal models of disease, or in coculture in vitro, were included in this review. The vessel density and other functional indexes, which were classified according to the organ source, were used to evaluate the efficiency of cotransplantation. Publication bias was assessed. There was no obvious difference in angiogenesis following combined cell transplantation (EPCs and MSCs) and transplantation of EPCs alone; however, an improvement in the function of damaged organs was observed following cotransplantation. In addition, combined cell transplantation significantly promoted tissue recovery in cardiovascular disease, cerebrovascular disease, and during bone regeneration. Compared with combined transplantation (EPCs and MSCs) and transplantation of MSCs alone, cotransplantation significantly promoted angiogenesis and bone regeneration, as well as vessel revascularization and tissue repair in cerebrovascular disease; however, no obvious effects on cardiovascular disease were observed. As an exploratory field in the discipline of tissue engineering, MSC and EPC cotransplantation offers advantages, although it is essential to assess the feasibility of this approach before clinical trials can be performed.

  2. Coronaviruses in brain tissue from patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Dessau, R B; Lisby, G; Frederiksen, J L

    2001-01-01

    Brain tissue from 25 patients with clinically definite multiple sclerosis (MS) and as controls brain tissue from 36 patients without neurological disease was tested for the presence of human coronaviral RNA. Four PCR assays with primers specific for N-protein of human coronavirus strain 229E and ...... in the proportion of positive signals from the MS patients compared to controls. Evidence for a chronic infection with the human coronaviruses strain 229E or OC43 in brain tissue from patients with MS or controls has not been found in this study.......Brain tissue from 25 patients with clinically definite multiple sclerosis (MS) and as controls brain tissue from 36 patients without neurological disease was tested for the presence of human coronaviral RNA. Four PCR assays with primers specific for N-protein of human coronavirus strain 229E...... and three PCR assays with primers specific for the nucleocapsid protein of human coronavirus strain OC43 were performed. Sporadic positive PCR assays were observed in both patients and controls in some of the PCR assays. However, these results were not reproducible and there was no difference...

  3. The case for regulatory compliance of electronic medical records about human tissue intended for transplantation.

    Science.gov (United States)

    Carrier, Robert

    2004-01-01

    It is vital that patients receiving human tissue by transplantation be able to trust in the suitability of the product. In short, patient safety must be ensured to the highest degree possible. To this end, firms operating tissue banks and those providing tissue donor coordination services are inspected by the U.S. Food and Drug Administration (FDA). The suitability of tissue for transplantation is objectively documented at all phases, beginning with donor screening. This process often involves the use of custom software applications that produce electronic medical records (EMRs) and databases that store the results. When a firm elects to keep the medical records relevant to human tissue products in electronic form, the record system must comply with applicable codified regulations. Unfortunately for the patient, many firms have yet to achieve regulatory compliance, and FDA enforcement is only beginning to approach the intensity appropriate to regulate this fast-growing industry. This article discusses current FDA trends in enforcement and rule-making related to human tissue intended for transplantation, as well as expectations the FDA has during an inspection.

  4. Two Distinct Processes of Bone-like Tissue Formation by Dental Pulp Cells after Tooth Transplantation

    Science.gov (United States)

    Yukita, Akira; Yoshiba, Kunihiko; Yoshiba, Nagako; Takahashi, Masafumi; Nakamura, Hiroaki

    2012-01-01

    Dental pulp is involved in the formation of bone-like tissue in response to external stimuli. However, the origin of osteoblast-like cells constructing this tissue and the mechanism of their induction remain unknown. We therefore evaluated pulp mineralization induced by transplantation of a green fluorescent protein (GFP)–labeled tooth into a GFP-negative hypodermis of host rats. Five days after the transplantation, the upper pulp cavity became necrotic; however, cell-rich hard tissue was observed adjacent to dentin at the root apex. At 10 days, woven bone-like tissue was formed apart from the dentin in the upper pulp. After 20 days, these hard tissues expanded and became histologically similar to bone. GFP immunoreactivity was detected in the hard tissue-forming cells within the root apex as well as in the upper pulp. Furthermore, immunohistochemical observation of α–smooth muscle actin, a marker for undifferentiated cells, showed a positive reaction in cells surrounding this bone-like tissue within the upper pulp but not in those within the root apex. Immunoreactivities of Smad4, Runx2, and Osterix were detected in the hard tissue-forming cells within both areas. These results collectively suggest that the dental pulp contains various types of osteoblast progenitors and that these cells might thus induce bone-like tissue in severely injured pulp. PMID:22899860

  5. Development of a transplantation transmission sentinel network to improve safety and traceability of organ and tissues.

    Science.gov (United States)

    Strong, D Michael; Seem, Debbie; Taylor, Gloria; Parker, Jory; Stewart, Darren; Kuehnert, Matthew J

    2010-11-01

    The US lags behind other developed countries in creating a system to monitor disease transmission and other complications from human allograft use, despite a pressing need. The risks of transmission are amplified in transplantation, since at least 8 organs and more than 100 tissues can be recovered from a single common organ and tissue donor. Moreover, since many allografts collected in the US are distributed internationally, tissue safety is a global concern. In June 2005, participants of a US government-sponsored workshop concluded that a communication network for the tracking and reporting of disease transmissions for tissues and organs was critically needed. The United Network for Organ Sharing (UNOS) entered into a cooperative agreement with the Centers for Disease Control and Prevention (CDC) in 2006 to develop a system prototype. Over the following 3 years, the Transplantation Transmission Sentinel Network (TTSN) was developed and piloted with the participation of organ procurement organizations, tissue banks and transplant centers. The prototype centered around three elements of data entry: (1) donation, (2) tissue implantation, and (3) adverse event. The pilot proved that a system can be built and operated successfully, but also suggested that users may be hesitant to report adverse events. CDC has requested further input on scope and cost to build a transplant surveillance infrastructure for a fully functional national system. For tissues however, in contrast to organs, tracking from recovery to implantation will be necessary before a system is operable, requiring common identifiers and nomenclature. Until a US sentinel network is operational, future transmission events that are preventable may result nationally and globally due to its absence.

  6. Effect of transplantation of muscle tissue in rats from the same litter on total number of flavins and FAD

    Directory of Open Access Journals (Sweden)

    S. N. Kobylnik

    2015-01-01

    Full Text Available Riboflavin is a member of redox enzymes involved in fatty acid oxidation and energy generation. Important role of this vitamin is in reproductive function. Exchange of transformation of riboflavin in animal tissues and cells of microorganisms include reactions that lead to synthesis and subsequent collapse of FMN and FAD. It is involved in enhancing antitumor activity of many anticancer drugs, as well as activation of the immune system to kill tumor cells. Issues of transport of riboflavin and its derivatives in animals have been studied enough. Investigations of changes of the balance of riboflavin and its metabolites in muscular tissues before transplantation in rats from one litter and at operation without replanting were conducted, based on the Udenfriend method of flavin determination. Transplantation in the experiment was carried out on white non-linear male rats weighing 180–300 g. Animals were taken out of the experiment by passing electric current through the medulla. Belly muscular tissue was taken from donor rats of the same litter, and that tissue was sewn to homological muscular tissue of the recipient. The same procedure was carried out with femoral muscular tissue. In the course of operation without replanting the same manipulations have been made except for transplantation stage (for determination of the effect of surgical intervention. Tissue not subject to any surgical intervention served as a control. Parameters of the study were measured on the first, third and seventh days after transplantation. Transplantation of muscular tissue caused no changes in total flavin amount. Content of RF + FMN after transplantation of muscular tissue in rats of the same litter decreased in femoral muscular tissue of the recipient. Transplantation of muscular tissues in rats from the same litter lead to increase in FAD amount in femoral muscular tissue of the donor and recipient on the third day of the experiment. Transplantation of femoral

  7. Concise Review: Bioprinting of Stem Cells for Transplantable Tissue Fabrication.

    Science.gov (United States)

    Leberfinger, Ashley N; Ravnic, Dino J; Dhawan, Aman; Ozbolat, Ibrahim T

    2017-10-01

    Bioprinting is a quickly progressing technology, which holds the potential to generate replacement tissues and organs. Stem cells offer several advantages over differentiated cells for use as starting materials, including the potential for autologous tissue and differentiation into multiple cell lines. The three most commonly used stem cells are embryonic, induced pluripotent, and adult stem cells. Cells are combined with various natural and synthetic materials to form bioinks, which are used to fabricate scaffold-based or scaffold-free constructs. Computer aided design technology is combined with various bioprinting modalities including droplet-, extrusion-, or laser-based bioprinting to create tissue constructs. Each bioink and modality has its own advantages and disadvantages. Various materials and techniques are combined to maximize the benefits. Researchers have been successful in bioprinting cartilage, bone, cardiac, nervous, liver, and vascular tissues. However, a major limitation to clinical translation is building large-scale vascularized constructs. Many challenges must be overcome before this technology is used routinely in a clinical setting. Stem Cells Translational Medicine 2017;6:1940-1948. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  8. The necessity of strengthening the cooperation between tissue banks and organ transplant organizations at national, regional, and international levels.

    Science.gov (United States)

    Morales Pedraza, Jorge

    2013-12-01

    The donation of tissues and organs increases significantly when tissue banks and organ transplant organizations work together in the procurement of organs and tissues at donor sources (hospitals, coroners system, organ procurement agencies, and funeral homes, among others). To achieve this important goal, national competent health authorities should considered the establishment of a mechanism that promote the widest possible cooperation between tissue banks and organ transplant organizations with hospitals, research medical institutions, universities, and other medical institutions and facilities. One of the issues that can facilitate this cooperation is the establishment of a coding and traceability system that could identify all tissues and organs used in transplant activities carried out in any country. The promotion of national, regional, and international cooperation between tissue banks and organ transplant organizations would enable the sharing of relevant information that could be important for medical practice and scientific studies carried out by many countries, particularly for those countries with a weak health care system.

  9. Similar liver transplantation survival with selected cardiac death donors and brain death donors

    NARCIS (Netherlands)

    Dubbeld, J.; Hoekstra, H.; Farid, W.; Ringers, J.; Porte, R. J.; Metselaar, H. J.; Baranski, A. G.; Kazemier, G.; van den Bere, A. P.; van Hoek, B.

    Background: The outcome of orthotopic liver transplantation (OLT) with controlled graft donation after cardiac death (DCD) is usually inferior to that with graft donation after brain death (DBD). This study compared outcomes from OLT with DBD versus controlled DCD donors with predefined restrictive

  10. Aluminium in brain tissue in familial Alzheimer's disease.

    Science.gov (United States)

    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.

  11. Brain tissue banking for stem cells for our future.

    Science.gov (United States)

    Palmero, Emily; Palmero, Sheryl; Murrell, Wayne

    2016-12-19

    In our lab we study neurogenesis and the development of brain tumors. We work towards treatment strategies for glioblastoma and towards using autologous neural stem cells for tissue regeneration strategies for brain damage and neurodegenerative disorders. It has been our policy to try to establish living cell cultures from all human biopsy material that we obtain. We hypothesized that small pieces of brain tissue could be cryopreserved and that live neural stem cells could be recovered at a later time. DMSO has been shown to possess a remarkable ability to diffuse through cell membranes and pass into cell interiors. Its chemical properties prevent the formation of damaging ice crystals thus allowing cell storage at or below -180 C. We report here a protocol for successful freezing of small pieces of tissue derived from human brain and human brain tumours. Virtually all specimens could be successfully revived. Assays of phenotype and behaviour show that the cell cultures derived were equivalent to those cultures previously derived from fresh tissue.

  12. MRI-Guided Biopsy to Correlate Tissue Specimens with MR Elastography Stiffness Readings in Liver Transplants

    Science.gov (United States)

    Perumpail, Ryan B.; Levitsky, Josh; Wang, Yi; Lee, Victoria S.; Karp, Jennifer; Jin, Ning; Yang, Guang-Yu; Bolster, Bradley D.; Shah, Saurabh; Zuehlsdorff, Sven; Nemcek, Albert A.; Larson, Andrew C.; Miller, Frank H.; Omary, Reed A.

    2012-01-01

    Rationale and Objectives Magnetic resonance elastography (MRE) can non-invasively measure the stiffness of liver tissue and display this information in anatomic maps. Magnetic resonance imaging (MRI)-guidance has not previously been used to biopsy segments of heterogeneous stiffness identified on MRE. Dedicated study of MRE in post-liver transplant patients is also limited. In this study, the ability of real-time MRI to guide biopsies of segments of the liver with different MRE stiffness values in the same post-transplant patient was assessed. Materials and Methods MRE was performed in 9 consecutive post-transplant patients with history of hepatitis C. Segments of highest and lower stiffness on MRE served as targets for subsequent real-time MRI-guided biopsy using T2-weighted imaging. The ability of MRI-guided biopsy to successfully obtain tissue specimens was assessed. The Wilcoxon Signed Rank Test was used to compare mean stiffness differences for highest and lower MRE stiffness segments, with α = 0.05. Results MRI-guidance allowed successful sampling of liver tissue for all (18/18) biopsies. There was a statistically significant difference in mean MRE stiffness values between highest (4.61 ± 1.99 kPa) and lower stiffness (3.03 ± 1.75 kPa) (P=0.0039) segments biopsied in the 9 post-transplant patients. Conclusion Real-time MRI can guide biopsy in patients after liver transplantation based upon MRE stiffness values. This study supports the use of MRI-guidance to sample tissue based upon functional information. PMID:22877987

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

    Science.gov (United States)

    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.

  14. Isolation of Borna Disease Virus from Human Brain Tissue

    Science.gov (United States)

    Nakamura, Yurie; Takahashi, Hirokazu; Shoya, Yuko; Nakaya, Takaaki; Watanabe, Makiko; Tomonaga, Keizo; Iwahashi, Kazuhiko; Ameno, Kiyoshi; Momiyama, Noriko; Taniyama, Hiroyuka; Sata, Tetsutaro; Kurata, Takeshi; de la Torre, Juan Carlos; Ikuta, Kazuyoshi

    2000-01-01

    Serological and molecular epidemiological studies indicate that Borna disease virus (BDV) can infect humans and is possibly associated with certain neuropsychiatric disorders. We examined brain tissue collected at autopsy from four schizophrenic patients and two healthy controls for the presence of BDV markers in 12 different brain regions. BDV RNA and antigen was detected in four brain regions of a BDV-seropositive schizophrenic patient (P2) with a very recent (2 years) onset of disease. BDV markers exhibited a regionally localized distribution. BDV RNA was found in newborn Mongolian gerbils intracranially inoculated with homogenates from BDV-positive brain regions of P2. Human oligodendroglia (OL) cells inoculated with brain homogenates from BDV-positive gerbils allowed propagation and isolation of BDVHuP2br, a human brain-derived BDV. Virus isolation was also possible by transfection of Vero cells with ribonucleoprotein complexes prepared from BDV-positive human and gerbil brain tissues. BDVHuP2br was genetically closely related to but distinct from previously reported human- and animal-derived BDV sequences. PMID:10775596

  15. Harvesting the living?: separating "brain death" and organ transplantation.

    Science.gov (United States)

    Campbell, Courtney S

    2004-09-01

    The chronic shortage of transplantable organs has reached critical proportions. In the wake of this crisis, some bioethicists have argued that there is sufficient public support to expand organ recovery through use of neocortical criteria of death or even pre-mortem organ retrieval. I present a typology of ways in which data gathered from the public can be misread or selectively used by bioethicists in service of an ideological or policy agenda, resulting in bad policy and bad ethics. Such risks should lead us to look at alternatives for increasing organ supplies short of expanding or abandoning the dead donor rule. The chronic problem of organ scarcity should prompt bioethicists to engage in constructive dialogue about the relation of the social sciences and bioethics, to examine the social malleability of the definition of death, and to revisit the question of the priority of organ transplants in the overall package of healthcare benefits provided to most, but not all, citizens.

  16. Airway Microbiota Determines Innate Cell Inflammatory or Tissue Remodeling Profiles in Lung Transplantation.

    Science.gov (United States)

    Bernasconi, Eric; Pattaroni, Céline; Koutsokera, Angela; Pison, Christophe; Kessler, Romain; Benden, Christian; Soccal, Paola M; Magnan, Antoine; Aubert, John-David; Marsland, Benjamin J; Nicod, Laurent P

    2016-11-15

    In lung transplant recipients, long-term graft survival relies on the control of inflammation and tissue remodeling to maintain graft functionality and avoid chronic lung allograft dysfunction. Although advances in clinical practice have improved transplant success, the mechanisms by which the balance between inflammation and remodeling is maintained are largely unknown. To assess whether host-microbe interactions in the transplanted lung determine the immunologic tone of the airways, and consequently could impact graft survival. Microbiota DNA and host total RNA were isolated from 203 bronchoalveolar lavages obtained from 112 patients post-lung transplantation. Microbiota composition was determined using 16S ribosomal RNA analysis, and expression of a set of genes involved in prototypic macrophage functions was quantified using real-time quantitative polymerase chain reaction. We show that the characteristics of the pulmonary microbiota aligned with distinct innate cell gene expression profiles. Although a nonpolarized activation was associated with bacterial communities consisting of a balance between proinflammatory (e.g., Staphylococcus and Pseudomonas) and low stimulatory (e.g., Prevotella and Streptococcus) bacteria, "inflammatory" and "remodeling" profiles were linked to bacterial dysbiosis. Mechanistic assays provided direct evidence that bacterial dysbiosis could lead to inflammatory or remodeling profiles in macrophages, whereas a balanced microbial community maintained homeostasis. The crosstalk between bacterial communities and innate immune cells potentially determines the function of the transplanted lung offering novel pathways for intervention strategies.

  17. Regeneration of Cartilaginous Tissue After Transplantation of Allofibroblasts

    OpenAIRE

    A. B. Tilyakov; B. A. Magrupov; M. D. Urazmetova; B. R. Karimov; B. S. Ubaydullaev; V. Kh. Sharipova

    2016-01-01

    Aim of investigation. To prove the usefulness of the use of embryonic fibroblasts for the regeneration of cartilaginous tissue.Material and methods. New experimental model of symphysis pubis rupture followed by its recovery was employed in 24 male Shinshilla rabbits (2.3—3.5 kg body mass) in 3 series of experiments. In the first series, reconstruction was not employed. In the 2nd series, the reconstruction of symphisis was performed with the aid of tantal wired cerclage (d=1.2 mm). In the 3d ...

  18. Progression of thanatophagy in cadaver brain and heart tissues

    Directory of Open Access Journals (Sweden)

    Gulnaz T. Javan

    2016-03-01

    Full Text Available Autophagy is an evolutionarily conserved catabolic process for maintaining cellular homeostasis during both normal and stress conditions. Metabolic reprogramming in tissues of dead bodies is inevitable due to chronic ischemia and nutrient deprivation, which are well-known features that stimulate autophagy. Currently, it is not fully elucidated whether postmortem autophagy, also known as thanatophagy, occurs in dead bodies is a function of the time of death. In this study, we tested the hypothesis that thanatophagy would increase in proportion to time elapsed since death for tissues collected from cadavers. Brain and heart tissue from corpses at different time intervals after death were analyzed by Western blot. Densitometry analysis demonstrated that thanatophagy occurred in a manner that was dependent on the time of death. The autophagy-associated proteins, LC3 II, p62, Beclin-1 and Atg7, increased in a time-dependent manner in heart tissues. A potent inducer of autophagy, BNIP3, decreased in the heart tissues as time of death increased, whereas the protein levels increased in brain tissues. However, there was no expression of BNIP3 at extended postmortem intervals in both brain and heart samples. Collectively, the present study demonstrates for the first time that thanatophagy occurs in brain and heart tissues of cadavers in a time-dependent manner. Further, our data suggest that cerebral thanatophagy may occur in a Beclin-1- independent manner. This unprecedented study provides potential insight into thanatophagy as a novel method for the estimation of the time of death in criminal investigationsAbstract: Autophagy is an evolutionarily conserved catabolic process for maintaining cellular homeostasis during both normal and stress conditions. Metabolic reprogramming in tissues of dead bodies is inevitable due to chronic ischemia and nutrient deprivation, which are well-known features that stimulate autophagy. Currently, it is not fully

  19. A High Rate Tension Device for Characterizing Brain Tissue

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael; 10.1177/1754337112436900

    2013-01-01

    The mechanical characterization of brain tissue at high loading velocities is vital for understanding and modeling Traumatic Brain Injury (TBI). The most severe form of TBI is diffuse axonal injury (DAI) which involves damage to individual nerve cells (neurons). DAI in animals and humans occurs at strains > 10% and strain rates > 10/s. The mechanical properties of brain tissues at these strains and strain rates are of particular significance, as they can be used in finite element human head models to accurately predict brain injuries under different impact conditions. Existing conventional tensile testing machines can only achieve maximum loading velocities of 500 mm/min, whereas the Kolsky bar apparatus is more suitable for strain rates > 100/s. In this study, a custom-designed high rate tension device is developed and calibrated to estimate the mechanical properties of brain tissue in tension at strain rates < 90/s, while maintaining a uniform velocity. The range of strain can also be extended to 100% de...

  20. Time Course of Cell Sheet Adhesion to Porcine Heart Tissue after Transplantation.

    Science.gov (United States)

    Chang, Dehua; Shimizu, Tatsuya; Haraguchi, Yuji; Gao, Shuai; Sakaguchi, Katsuhisa; Umezu, Mitsuo; Yamato, Masayuki; Liu, Zhongmin; Okano, Teruo

    2015-01-01

    Multilayered cell sheets have been produced from bone marrow-derived mesenchymal stem cells (MSCs) for investigating their adhesion properties onto native porcine heart tissue. Once MSCs reached confluence after a 7-day culture on a temperature-responsive culture dish, a MSCs monolayer spontaneously detached itself from the dish, when the culture temperature was reduced from 37 to 20°C. The basal extracellular matrix (ECM) proteins of the single cell sheet are preserved, because this technique requires no proteolytic enzymes for harvesting cell sheet, which become a basic building block for assembling a multilayer cell sheet. The thickness of multilayered cell sheets made from three MSC sheets was found to be approximately 60 μm. For investigating the adhesion properties of the basal and apical sides, the multilayered cell sheets were transplanted onto the surface of the heart's left ventricle. Multilayered cell sheets were histological investigated at 15, 30, 45 and 60 minutes after transplantation by hematoxylin eosin (HE) and azan dyes to determine required time for the adhesion of the multilayered sheets following cell-sheet transplantation. The results showed that only the basal side of multilayered cell sheets significantly enhanced the sheets adhesion onto the surface of heart 30 minutes after transplantation. This study concluded that (1) cell sheets had to be transplanted with its basal side onto the surface of heart tissue and (2) at least 30 minutes were necessary for obtaining the histological adhesion of the sheets to the heart tissue. This study provided clinical evidence and parameters for the successful application of MSC sheets to the myocardium and allowed cell sheet technology to be adapted clinical cell-therapy for myocardial diseases.

  1. Integrity of the Oral Tissues in Patients with Solid-Organ Transplants

    Directory of Open Access Journals (Sweden)

    Gonzalo Rojas

    2012-01-01

    Full Text Available The relationship between the use of immunosuppressants in solid-organ transplant patients and oral tissue abnormalities has been recognized. The objective of this study was to determine the state of oral tissue integrity in renal, heart, and liver transplant patients who are on continuous medical and dental control. Forty patients of both sexes were clinically evaluated at the Clinical Hospital of the University of Chile to identify pathologies of oral mucosa, gingival enlargement (GE, decayed, missing, filled teeth (DMFT index, and salivary flow. The average age of the transplant subjects was 49.4 years, and the age range was 19 to 69 years. Most subjects maintained a good level of oral hygiene, and the rate mean of DMFT was 14.7. The degree of involvement of the oral mucosa and GE was low (10%. Unlike other studies, the frequency of oral mucosal diseases and GE was low despite the fact that these patients were immunosuppressed. Care and continuous monitoring seem to be of vital importance in maintaining the oral health of transplant patients.

  2. Confocal laser scanning microscopy evaluation of an acellular dermis tissue transplant (Epiflex®.

    Directory of Open Access Journals (Sweden)

    Eric Dominic Roessner

    Full Text Available The structure of a biological scaffold is a major determinant of its biological characteristics and its interaction with cells. An acellular dermis tissue transplant must undergo a series of processing steps, to remove cells and genetic material and provide the sterility required for surgical use. During manufacturing and sterilization the structure and composition of tissue transplants may change. The composition of the human cell-free dermis transplant Epiflex® was investigated with specific attention paid to its structure, matrix composition, cellular content and biomechanics. We demonstrated that after processing, the structure of Epiflex remains almost unchanged with an intact collagen network and extracellular matrix (ECM protein composition providing natural cell interactions. Although the ready to use transplant does contain some cellular and DNA debris, the processing procedure results in a total destruction of cells and active DNA which is a requirement for an immunologically inert and biologically safe substrate. Its biomechanical parameters do not change significantly during the processing.

  3. Discovery of Undescribed Brain Tissue Changes Around Implanted Microelectrode Arrays

    Directory of Open Access Journals (Sweden)

    Himanshi Desai

    2012-01-01

    Full Text Available Brain-implantable microelectrode arrays are devicesdesigned to record or electrically stimulate the activity ofneurons in the brain. These devices hold the potential tohelp treat epilepsy, paralysis, blindness, and deafness, andalso provide researchers with insights into a varietyof neural processes, such as memory formation.While these devices have a very promising future,researchers are discovering that their long-termfunctionality is greatly limited by the brain’s naturalimmune response to foreign objects. To improve thefunctional lifetime of these devices, one solution lies infully characterizing and understanding this tissue response.Roles for microglia and astrocytes in this biologicalresponse have been characterized. However, changesto oligodendrocytes, cells that myelinate axons, remainpoorly understood. These cells provide insulationto the axons, which is required for proper neuralfunctioning. Here we report on the changes that occurwith oligodendrocyte processes in tissue aroundmicroelectrode implants in the brain.Six rats were surgically implanted with microelectrodearrays and allowed to recover for 1, 2, or 4 weeks.Subjects were then sacrificed and the brain tissue wasprocessed using our recently developed method, Device-Capture Histology. Immunohistochemistry and confocalmicroscopy was employed to assess the responsearound the device. Results indicated a decrease inoligodendrocyte density and a loss in typical directionalorientation of oligodendrocyte processes in tissue near thedevice. These results suggest alterations in the underlyingneuronal networks around these devices, which maygreatly impact the current functional utility of thesepromising devices.

  4. Histopathological changes in the Brain Tissue of Africa Catfish ...

    African Journals Online (AJOL)

    ... post juvenile African catfish C. gariepinus as characterized by severe degeneration of dark-stained purkinje neurons, oedema, vacuolar changes with empty spaces which appeared as moth eaten area and showed proliferation of glial cells. There is need for more research work on the histopathology of brain tissue of fish ...

  5. Detection of Rabies Antigen in the Brain Tissues of Apparetly ...

    African Journals Online (AJOL)

    Rabies is a serious public health hazard and recently outbreaks of the disease have been reported in three local government areas in Cross River State. Detection of rabies antigen in the brain tissues of apparently healthy dogs indicates the presence of rabies virus and this is a significant factor in the transmission and ...

  6. A novel three-phase model of brain tissue microstructure.

    Directory of Open Access Journals (Sweden)

    Jana L Gevertz

    Full Text Available We propose a novel biologically constrained three-phase model of the brain microstructure. Designing a realistic model is tantamount to a packing problem, and for this reason, a number of techniques from the theory of random heterogeneous materials can be brought to bear on this problem. Our analysis strongly suggests that previously developed two-phase models in which cells are packed in the extracellular space are insufficient representations of the brain microstructure. These models either do not preserve realistic geometric and topological features of brain tissue or preserve these properties while overestimating the brain's effective diffusivity, an average measure of the underlying microstructure. In light of the highly connected nature of three-dimensional space, which limits the minimum diffusivity of biologically constrained two-phase models, we explore the previously proposed hypothesis that the extracellular matrix is an important factor that contributes to the diffusivity of brain tissue. Using accurate first-passage-time techniques, we support this hypothesis by showing that the incorporation of the extracellular matrix as the third phase of a biologically constrained model gives the reduction in the diffusion coefficient necessary for the three-phase model to be a valid representation of the brain microstructure.

  7. Adult Tissue-Derived Stem Cells and Tolerance Induction in Nonhuman Primates for Vascularized Composite Allograft Transplantation

    Science.gov (United States)

    2017-10-01

    Allograft Transplantation PRINCIPAL INVESTIGATOR: Eric A. Elster, MD RECIPIENT: The Henry M. Jackson Foundation for the Advancement of Military ...Advancement of Military Medicine. 6720A Rockledge Drive, Suite #100, Bethesda, MD 20817-1834 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING...Distribution Unlimited 13. SUPPLEMENTARY NOTES The utilization of adult derived adipose stem cells administration in composite tissue transplantation

  8. General solutions to poroviscoelastic model of hydrocephalic human brain tissue.

    Science.gov (United States)

    Mehrabian, Amin; Abousleiman, Younane

    2011-12-21

    Hydrocephalus is a well-known disorder of brain fluidic system. It is commonly associated with complexities in cerebrospinal fluid (CSF) circulation in brain. In this paper, hydrocephalus and shunting surgery which is used in its treatment are modeled. Brain tissues are considered to follow a poroviscoelastic constitutive model in order to address the effects of time dependence of mechanical properties of soft tissues and fluid flow hydraulics. Our solution draws from Biot's theory of poroelasticity, generalized to account for viscoelastic effects through the correspondence principle. Geometrically, the brain is conceived to be spherically symmetric, where the ventricles are assumed to be a hollow concentric space filled with cerebrospinal fluid. A generalized Kelvin model is considered for the rheological properties of brain tissues. The solution presented is useful in the analysis of the disorder of hydrocephalus as well as the treatment associated with it, namely, ventriclostomy surgery. The sensitivity of the solution to various factors such as aqueduct blockage level and trabeculae stiffness is thoroughly analyzed using numerical examples. Results indicate that partial aqueduct stenosis may be a cause of hydrocephalus. However, only severe occlusion of the aqueduct can cause a significant increase in the ventricle and brain's extracellular fluid pressure. Ventriculostomy shunts are commonly used as a remedy to hydrocephalus. They serve to reduce the ventricular pressure to the normal level. However, sensitivity analysis on the shunt's fluid deliverability parameter has shown that inappropriate design or selection of design shunt may cause under-drainage or over-drainage of the ventricles. Excessive drainage of CSF may increase the normal tensile stress on trabeculae. It can cause rupture of superior cerebral veins or damage to trabeculae or even brain tissues which in turn may lead to subdural hematoma, a common side-effect of the surgery. These Post

  9. Faecal microbiota transplantation: a sui generis biological drug, not a tissue.

    Science.gov (United States)

    Megerlin, F; Fouassier, E; Lopert, R; Bourlioux, P

    2014-07-01

    Responding to Smith et al. (Nature, 2014), this paper argues that for medical use, faecal microbiota transplantation (FMT) should be considered a sui generis biological drug, rather than a tissue. Smith and colleagues' thesis is based on possible undesirable economic consequences of this designation--not on its scientific and conceptual basis. The faecal transplant (including gut microbiota, metabolites, mucus, human cells, viruses, fungi, etc.) is not a tissue; it is of topographic--not cellular--human origin. We consider the donor a bioreactor, producing the faecal substrate of therapeutic interest. The debate is of singular importance as the FDA considers FMT a drug and released a new guidance for public consultation in February 2014, whereas to date the European Medicines Agency has not promulgated its position. The UK's National Institute for Heath and Care Excellence does not consider FMT to involve the transplantation of body tissue, and in March 2014 the French regulatory agency ANSM expressly declared it to be a drug. As FM is a complex and highly variable admixture, its components cannot be completely characterized, and to date, compositional quality cannot be assessed. We consider FMT to be a sui generis biologic drug, albeit one prepared with unconventional raw material under microbiologic control. The possibility of associating identified bacterial species with particular diseases and cultivating selected bacteria of therapeutic interest would certainly define a second generation of microbiome therapeutics, but is still speculative. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  10. Intrahepatic Tissue Implantation Represents a Favorable Approach for Establishing Orthotopic Transplantation Hepatocellular Carcinoma Mouse Models.

    Directory of Open Access Journals (Sweden)

    Quan Rao

    Full Text Available Mouse models are commonly used for studying hepatocellular carcinoma (HCC biology and exploring new therapeutic interventions. Currently three main modalities of HCC mouse models have been extensively employed in pre-clinical studies including chemically induced, transgenic and transplantation models. Among them, transplantation models are preferred for evaluating in vivo drug efficacy in pre-clinical settings given the short latency, uniformity in size and close resemblance to tumors in patients. However methods used for establishing orthotopic HCC transplantation mouse models are diverse and fragmentized without a comprehensive comparison. Here, we systemically evaluate four different approaches commonly used to establish HCC mice in preclinical studies, including intravenous, intrasplenic, intrahepatic inoculation of tumor cells and intrahepatic tissue implantation. Four parameters--the latency period, take rates, pathological features and metastatic rates--were evaluated side-by-side. 100% take rates were achieved in liver with intrahepatic, intrasplenic inoculation of tumor cells and intrahepatic tissue implantation. In contrast, no tumor in liver was observed with intravenous injection of tumor cells. Intrahepatic tissue implantation resulted in the shortest latency with 0.5 cm (longitudinal diameter tumors found in liver two weeks after implantation, compared to 0.1cm for intrahepatic inoculation of tumor cells. Approximately 0.1cm tumors were only visible at 4 weeks after intrasplenic inoculation. Uniform, focal and solitary tumors were formed with intrahepatic tissue implantation whereas multinodular, dispersed and non-uniform tumors produced with intrahepatic and intrasplenic inoculation of tumor cells. Notably, metastasis became visible in liver, peritoneum and mesenterium at 3 weeks post-implantation, and lung metastasis was visible after 7 weeks. T cell infiltration was evident in tumors, resembling the situation in HCC patients

  11. Inhibition of chemokine-glycosaminoglycan interactions in donor tissue reduces mouse allograft vasculopathy and transplant rejection.

    Directory of Open Access Journals (Sweden)

    Erbin Dai

    2010-05-01

    Full Text Available Binding of chemokines to glycosaminoglycans (GAGs is classically described as initiating inflammatory cell migration and creating tissue chemokine gradients that direct local leukocyte chemotaxis into damaged or transplanted tissues. While chemokine-receptor binding has been extensively studied during allograft transplantation, effects of glycosaminoglycan (GAG interactions with chemokines on transplant longevity are less well known. Here we examine the impact of interrupting chemokine-GAG interactions and chemokine-receptor interactions, both locally and systemically, on vascular disease in allografts.Analysis of GAG or CC chemokine receptor 2 (CCR2 deficiency were coupled with the infusion of viral chemokine modulating proteins (CMPs in mouse aortic allograft transplants (n = 239 mice. Inflammatory cell invasion and neointimal hyperplasia were significantly reduced in N-deacetylase-N-sulfotransferase-1 (Ndst1(f/fTekCre(+ heparan sulfate (GAG-deficient (Ndst1(-/-, p<0.044 and CCR2-deficient (Ccr2(-/-, p<0.04 donor transplants. Donor tissue GAG or CCR2 deficiency markedly reduced inflammation and vasculopathy, whereas recipient deficiencies did not. Treatment with three CMPs was also investigated; Poxviral M-T1 blocks CC chemokine receptor binding, M-T7 blocks C, CC, and CXC GAG binding, and herpesviral M3 binds receptor and GAG binding for all classes. M-T7 reduced intimal hyperplasia in wild type (WT (Ccr2(+/+, p< or =0.003 and Ccr2(-/-, ptransplants (p< or =0.001.Interruption of chemokine-GAG interactions, even in the absence of chemokine-receptor blockade, is a highly effective approach to reduction of

  12. Transplantation of tissue-engineered human corneal endothelium in cat models.

    Science.gov (United States)

    Fan, Tingjun; Ma, Xiya; Zhao, Jun; Wen, Qian; Hu, Xiuzhong; Yu, Haoze; Shi, Weiyun

    2013-01-01

    To evaluate the performance of reconstructed tissue-engineered human corneal endothelium (TE-HCE) by corneal transplantation in cat models. TE-HCE reconstruction was performed by culturing 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled monoclonal HCE cells on denuded amniotic membranes (dAMs) in 20% fetal bovine serum-containing Dulbecco's Modified Eagle's Medium/Ham's Nutrient Mixture F12 (1:1) medium and 5% CO(2) at 37 ° C on a 24-well culture plate. The reconstructed TE-HCE was transplanted into cat corneas via lamellar keratoplasty with all of the endothelium and part of Descemet's membrane stripped. Postsurgical corneas were monitored daily with their histological properties examined during a period of 104 days after transplantation. The reconstructed TE-HCE at a density of 3,413.33 ± 111.23 cells/mm(2) in average established intense cell-cell and cell-dAM junctions. After lamellar keratoplasty surgery, no obvious edema was found in TE-HCE-transplanted cat corneas, which were transparent throughout the monitoring period. In contrast, intense corneal edema developed in dAM-transplanted cat corneas, which were turbid. The corneal thickness gradually decreased to 751.33 ± 11.37 μm on day 104 after TE-HCE transplantation, while that of dAM eye was over 1,000 μm in thickness during the monitoring period. A monolayer of endothelium consisting of TE-HCE-originated cells at a density of 2,573.33 ± 0.59 cells/mm(2) attached tightly to the surface of remnant Descemet's membrane over 104 days; this was similar to the normal eye control in cell density. The reconstructed TE-HCE was able to function as a corneal endothelium equivalent and restore corneal function in cat models.

  13. Determination of Friction Coefficient in Unconfined Compression of Brain Tissue

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael; 10.1016/j.jmbbm.2012.05.001

    2013-01-01

    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 for 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 mu 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 mu was equal to 0.09 +/- 0.03, 0.18 +/- 0.04, 0.18 +/- 0.04 and 0.20 +/- 0.02 at strain rates of...

  14. Should we clone human beings? Cloning as a source of tissue for transplantation.

    Science.gov (United States)

    Savulescu, J

    1999-01-01

    The most publicly justifiable application of human cloning, if there is one at all, is to provide self-compatible cells or tissues for medical use, especially transplantation. Some have argued that this raises no new ethical issues above those raised by any form of embryo experimentation. I argue that this research is less morally problematic than other embryo research. Indeed, it is not merely morally permissible but morally required that we employ cloning to produce embryos or fetuses for the sake of providing cells, tissues or even organs for therapy, followed by abortion of the embryo or fetus. PMID:10226910

  15. TRANSPLANTATION

    African Journals Online (AJOL)

    Background: Laparoscopic donor nephrectomy has become the procedure of choice for living donor kidney transplantation in many centres. We report on ... to acute rejection which required exploration and transplant nephrectomy. Reoperation was .... an increased risk of premature graft failure and worsened residual graft ...

  16. Magnetic resonance electric property imaging of brain tissues.

    Science.gov (United States)

    Zhang, Xiaotong; Zhu, Shanan; He, Bin

    2009-01-01

    The electric properties (EPs) of brain tissues, i.e., the electric conductivity and permittivity, can provide important information for diagnosis of various brain disorders. A high-field MRI system is accompanied by significant wave propagation effects, and the radio frequency (RF) radiation is dependent on EPs of the biological tissue. Based on the measurement of the active transverse magnetic component of the applied RF field (known as B1-mapping technique), we have developed a dual-excitation algorithm, which uses two sets of measured B1 data, to noninvasively reconstruct the biological tissue's electric properties. A series of computer simulations were conducted to evaluate the feasibility and performance of the proposed method on a 3-D head model within a birdcage coil and a transverse electromagnetic coil. Compared with other B1-mapping based reconstruction algorithms, our approach provides superior performance without the need for iterative computations. The present simulation results indicate good reconstruction of electric properties of brain tissues from noninvasive MRI B1 mapping.

  17. Autologous subcutaneous adipose tissue transplants improve adipose tissue metabolism and reduce insulin resistance and fatty liver in diet-induced obesity rats.

    Science.gov (United States)

    Torres-Villalobos, Gonzalo; Hamdan-Pérez, Nashla; Díaz-Villaseñor, Andrea; Tovar, Armando R; Torre-Villalvazo, Ivan; Ordaz-Nava, Guillermo; Morán-Ramos, Sofía; Noriega, Lilia G; Martínez-Benítez, Braulio; López-Garibay, Alejandro; Torres-Landa, Samuel; Ceballos-Cantú, Juan C; Tovar-Palacio, Claudia; Figueroa-Juárez, Elizabeth; Hiriart, Marcia; Medina-Santillán, Roberto; Castillo-Hernández, Carmen; Torres, Nimbe

    2016-09-01

    Long-term dietary and pharmacological treatments for obesity have been questioned, particularly in individuals with severe obesity, so a new approach may involve adipose tissue transplants, particularly autologous transplants. Thus, the aim of this study was to evaluate the metabolic effects of autologous subcutaneous adipose tissue (SAT) transplants into two specific intraabdominal cavity sites (omental and retroperitoneal) after 90 days. The study was performed using two different diet-induced obesity (DIO) rat models: one using a high-fat diet (HFD) and the other using a high-carbohydrate diet (HCHD). Autologous SAT transplant reduced hypertrophic adipocytes, improved insulin sensitivity, reduced hepatic lipid content, and fasting serum-free fatty acids (FFAs) concentrations in the two DIO models. In addition, the reductions in FFAs and glycerol were accompanied by a greater reduction in lipolysis, assessed via the phosphorylation status of HSL, in the transplanted adipose tissue localized in the omentum compared with that localized in the retroperitoneal compartment. Therefore, the improvement in hepatic lipid content after autologous SAT transplant may be partially attributed to a reduction in lipolysis in the transplanted adipose tissue in the omentum due to the direct drainage of FFAs into the liver. The HCHD resulted in elevated fasting and postprandial serum insulin levels, which were dramatically reduced by the autologous SAT transplant. In conclusion, the specific intraabdominal localization of the autologous SAT transplant improved the carbohydrate and lipid metabolism of adipose tissue in obese rats and selectively corrected the metabolic parameters that are dependent on the type of diet used to generate the DIO model. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  18. [Neurotropic effects of heptapeptide mystixin studied on brain tissue sections].

    Science.gov (United States)

    Mokrushin, A A

    2011-01-01

    Neurotropic effects of heptapeptide mystixin have been studied on olfactory cortex neurons in rat brain tissue sections. The application of mystixin onto brain section produced a dose-dependent inhibition of AMPA- and NMDA-receptor-dependent processes. The peptide suppressed the activity of inhibitory processes only at small doses (10, 25, and 50 mg/ml) and potentiated these processes at greater doses (100 and 250 mg/ml). These effects of mystixin are reversible: after washing, the activities of both exciting (except for NMDA-related) and inhibitory mechanisms were restored.

  19. Biocompatibility and functionality of a tissue-engineered living corneal stroma transplanted in the feline eye.

    Science.gov (United States)

    Boulze Pankert, Marie; Goyer, Benjamin; Zaguia, Fatma; Bareille, Myriam; Perron, Marie-Claude; Liu, Xinling; Cameron, J Douglas; Proulx, Stéphanie; Brunette, Isabelle

    2014-10-02

    Corneal tissue shortage has become a major concern worldwide, which has motivated the search for alternative solutions to eye bank human eyes for corneal transplantation. Minimally invasive lamellar transplantation and tissue engineering may offer new opportunities for the rehabilitation of diseased corneas. The aim of this study was to evaluate the biocompatibility and functionality of stromal lamellar grafts tissue-engineered (TE) in vitro and transplanted in vivo in the cornea of a feline model. The corneal stromas were engineered in culture from corneal stromal cells using the self-assembly approach, without the addition of exogenous material or scaffold. Eight healthy animals underwent two intrastromal grafts in one eye and the contralateral eye was used as a control. Animals were followed with slit-lamp ophthalmic examination, corneal esthesiometry and optical coherent tomography. Confocal microscopy, immunofluorescence, histology, and transmission electron microscopy (TEM) were performed at 4 months. Four months after transplantation, the TE-stromal grafts were transparent, functional, and well tolerated by the eye. All grafts remained avascular, with no signs of immune rejection, despite a short course of low-dose topical steroids. Corneal sensitivity returned to preoperative level and reinnervation of the grafts was confirmed by confocal microscopy and immunofluorescence. Histology and TEM of the TE-grafts showed a lamellar stromal structure with regular collagen fibril arrangement. These results open the way to an entirely new therapeutic modality. Intracorneal filling using a biocompatible, transparent, and malleable TE-stroma could be the basis for multiple types of novel therapeutic options in corneal interventional surgery. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  20. Mechanisms of Tolerance to Parental Parathyroid Tissue when Combined with Human Allogeneic Thymus Transplantation

    Science.gov (United States)

    Chinn, Ivan K.; Olson, John A.; Skinner, Michael A.; McCarthy, Elizabeth A.; Gupton, Stephanie E.; Chen, Dong-Feng; Bonilla, Francisco A.; Roberts, Robert L.; Kanariou, Maria G.; Devlin, Blythe H.; Markert, M. Louise

    2010-01-01

    Background The induction of tolerance toward third-party solid organ grafts with allogeneic thymus tissue transplantation has not been previously demonstrated in human subjects. Objective Infants with complete DiGeorge anomaly (having neither thymus nor parathyroid function) were studied for conditions and mechanisms required for the development of tolerance to third-party solid organ tissues. Methods Four infants who met criteria received parental parathyroid with allogeneic thymus transplantation and were studied. Results Two of three survivors showed function of both grafts but subsequently lost parathyroid function. They demonstrated alloreactivity against the parathyroid donor in mixed lymphocyte cultures. For these 2 recipients, parathyroid donor HLA class II alleles were mismatched with the recipient and thymus. MHC class II tetramers confirmed the presence of recipient CD4+ T cells with specificity towards a mismatched parathyroid donor class II allele. The third survivor has persistent graft function and lacks alloreactivity towards the parathyroid donor. All parathyroid donor class II alleles were shared with either the recipient or the thymus graft, with minor differences between the parathyroid (HLA-DRB1*1104) and thymus (HLA-DRB1*1101). Tetramer analyses detected recipient T cells specific for the parathyroid HLA-DRB1*1104 allele. Alloreactivity towards the parathyroid donor was restored with low-doses of IL-2. Conclusion Tolerance toward parathyroid grafts in combined parental parathyroid and allogeneic thymus transplantation requires matching of thymus tissue to parathyroid HLA class II alleles to promote negative selection and suppression of recipient T cells that have alloreactivity toward the parathyroid grafts. This matching strategy may be applied toward tolerance induction in future combined thymus and solid organ transplantation efforts. PMID:20832849

  1. In vivo mapping of current density distribution in brain tissues during deep brain stimulation (DBS)

    Science.gov (United States)

    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.

  2. Regional mechanical properties of human brain tissue for computational models of traumatic brain injury.

    Science.gov (United States)

    Finan, John D; Sundaresh, Sowmya N; Elkin, Benjamin S; McKhann, Guy M; Morrison, Barclay

    2017-06-01

    To determine viscoelastic shear moduli, stress relaxation indentation tests were performed on samples of human brain tissue resected in the course of epilepsy surgery. Through the use of a 500µm diameter indenter, regional mechanical properties were measured in cortical grey and white matter and subregions of the hippocampus. All regions were highly viscoelastic. Cortical grey matter was significantly more compliant than the white matter or hippocampus which were similar in modulus. Although shear modulus was not correlated with the age of the donor, cortex from male donors was significantly stiffer than from female donors. The presented material properties will help to populate finite element models of the brain as they become more anatomically detailed. We present the first mechanical characterization of fresh, post-operative human brain tissue using an indentation loading mode. Indentation generates highly localized data, allowing structure-specific mechanical properties to be determined from small tissue samples resected during surgery. It also avoids pitfalls of cadaveric tissue and allows data to be collected before degenerative processes alter mechanical properties. To correctly predict traumatic brain injury, finite element models must calculate intracranial deformation during head impact. The functional consequences of injury depend on the anatomical structures injured. Therefore, morbidity depends on the distribution of deformation across structures. Accurate prediction of structure-specific deformation requires structure-specific mechanical properties. This data will facilitate deeper understanding of the physical mechanisms that lead to traumatic brain injury. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. Assessing fibrinogen extravasation into Alzheimer's disease brain using high-content screening of brain tissue microarrays.

    Science.gov (United States)

    Narayan, Pritika J; Kim, Sue-Ling; Lill, Claire; Feng, Sheryl; Faull, Richard L M; Curtis, Maurice A; Dragunow, Michael

    2015-05-30

    Tissue microarrays are commonly used to evaluate disease pathology however methods to automate and quantify pathological changes are limited. This article demonstrates the utility of the VSlide scanner (MetaSystems) for automated image acquisition from immunolabelled tissue microarray slides, and subsequent automated image analysis with MetaXpress (Molecular Devices) software to obtain objective, efficient and reproducible data from immunolabelled tissue microarray sections. Significant increases in fibrinogen immunolabelling were observed in 29 Alzheimer's disease cases compared to 28 control cases analysed from a single tissue microarray slide. Western blot analysis also demonstrated significant increases in fibrinogen immunolabelling in 6 Alzheimer's cases compared to 6 control cases. The observed changes were also validated with gold standard blinded manual H-scoring. VSlide Metafer software offers a 'tissue microarray acquisition' plugin for easy mapping of tissue cores with their original position on the tissue microarray map. High resolution VSlide images are compatible with MetaXpress image analysis software. This article details the coupling of these two technologies to accurately and reproducibly analyse immunolabelled tissue microarrays within minutes, compared to the gold standard method of manual counting using H-scores which is significantly slower and prone to inter-observer variation. Here, we couple brain tissue microarray technology with high-content screening and automated image analysis as a powerful way to address bottle necks in data generation and improve throughput, as well as sensitivity to study biological/pathological changes in brain disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Whole-brain 3D mapping of human neural transplant innervation.

    Science.gov (United States)

    Doerr, Jonas; Schwarz, Martin Karl; Wiedermann, Dirk; Leinhaas, Anke; Jakobs, Alina; Schloen, Florian; Schwarz, Inna; Diedenhofen, Michael; Braun, Nils Christian; Koch, Philipp; Peterson, Daniel A; Kubitscheck, Ulrich; Hoehn, Mathias; Brüstle, Oliver

    2017-01-19

    While transplantation represents a key tool for assessing in vivo functionality of neural stem cells and their suitability for neural repair, little is known about the integration of grafted neurons into the host brain circuitry. Rabies virus-based retrograde tracing has developed into a powerful approach for visualizing synaptically connected neurons. Here, we combine this technique with light sheet fluorescence microscopy (LSFM) to visualize transplanted cells and connected host neurons in whole-mouse brain preparations. Combined with co-registration of high-precision three-dimensional magnetic resonance imaging (3D MRI) reference data sets, this approach enables precise anatomical allocation of the host input neurons. Our data show that the same neural donor cell population grafted into different brain regions receives highly orthotopic input. These findings indicate that transplant connectivity is largely dictated by the circuitry of the target region and depict rabies-based transsynaptic tracing and LSFM as efficient tools for comprehensive assessment of host-donor cell innervation.

  5. Inhomogeneous Deformation of Brain Tissue During Tension Tests

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael D; 10.1016/j.commatsci.2012.05.030

    2013-01-01

    Mechanical characterization of brain tissue has been investigated extensively by various research groups over the past fifty years. These properties are particularly important for modelling Traumatic Brain Injury (TBI). In this research, we present the design and calibration of a High Rate Tension Device (HRTD) capable of performing tests up to a maximum strain rate of 90/s. We use experimental and numerical methods to investigate the effects of inhomogeneous deformation of porcine brain tissue during tension at different specimen thicknesses (4.0-14.0 mm), by performing tension tests at a strain rate of 30/s. One-term Ogden material parameters (mu = 4395.0 Pa, alpha = -2.8) were derived by performing an inverse finite element analysis to model all experimental data. A similar procedure was adopted to determine Young's modulus (E= 11200 Pa) of the linear elastic regime. Based on this analysis, brain specimens of aspect ratio (diameter/thickness) S < 1.0 are required to minimise the effects of inhomogeneous...

  6. Distribution of opiate alkaloids in brain tissue of experimental animals

    Science.gov (United States)

    Pilija, Vladimir; Mimica-Dukic, Neda; Budakov, Branislav; Cvjeticanin, Stanko

    2012-01-01

    The present study examined regional distribution of opiate alkaloids from seized heroin in brain regions of experimental animals in order to select parts with the highest content of opiates. Their analysis should contribute to resolve causes of death due to heroin intake. The tests were performed at different time periods (5, 15, 45 and 120 min) after male and female Wistar rats were treated with seized heroin. Opiate alkaloids (codeine, morphine, acetylcodeine, 6-acetylmorphine and 3,6-diacetylmorphine) were quantitatively determined in brain regions known for their high concentration of µ-opiate receptors: cortex, brainstem, amygdala and basal ganglia, by using gas chromatography–mass spectrometry (GC–MS). The highest content of opiate alkaloids in the brain tissue of female animals was found 15 min and in male animals 45 min after treatment. The highest content of opiates was determined in the basal ganglia of the animals of both genders, indicating that this part of brain tissue presents a reliable sample for identifying and assessing contents of opiates after heroin intake. PMID:23554560

  7. Nurses' attitudes and knowledge regarding organ and tissue donation and transplantation in a provincial hospital: A descriptive and multivariate analysis.

    Science.gov (United States)

    Lomero, Maria Del Mar; Jiménez-Herrera, María F; Rasero, Maria José; Sandiumenge, Alberto

    2017-09-01

    The attitudes and knowledge of nursing personnel regarding organ and tissue donation can influence the decision to donate. This study aimed to determine these two factors among nurses at a district hospital in Barcelona, Spain. A survey was carried out using a 35 item questionnaire. Results were subjected to descriptive and comparative statistical analyses using bivariate and multivariate analyses to examine the relation between demographic data and attitudes toward donation. The completion rate was 68.2%, with 98.6% of those responding stating that they were in favor of organ donation. The respondents were unsure as to whether the criteria for inclusion in transplant waiting lists were appropriate (57.5%), whereas 72.2% agreed that brain death is equivalent to death. The bivariate analysis revealed a significant association between a positive attitude toward donation and working on permanent night shift no religious beliefs. Attitudes toward donation among nurses were generally positive; a negative attitude, although attitudes towards donation among the nurses participating in the study were generally positive, it should be pointed out that when a negative attitude does exist this affects significant aspects such as belief in the diagnosis of brain death or the criteria for inclusion on the waiting list, amongst others, which reflects that specific training in donation focused on nurses continues to be needed. © 2017 John Wiley & Sons Australia, Ltd.

  8. Prevalence of positive microbiology results from donor cornea tissue in different methods of corneal transplantation.

    Science.gov (United States)

    Garg, Sumit; Said, Bishoy; Farid, Marjan; Steinert, Roger F

    2013-02-01

    To evaluate the prevalence of positive microbiology results (culture and/or Gram stain) in donor cornea tissue with newer transplant methods and to assess if the results subsequently correlate with higher incidence of clinical infection. A retrospective review of the microbiology records of 569 consecutive corneal transplants from July 2006 through July 2010 was performed to evaluate positive microbiology results in routine evaluation of cornea donor tissue. Microbiologic results were available for 544 of 569 transplants. The remaining 25 cases did not have specimens submitted for microbiologic analysis. In cases with results available, 46 (8.5%) positive reports occurred. In 10 of the 46 cases, Gram stain results were positive with subsequent negative cultures. Analysis revealed that the prevalence of positive results was 6 in 137 (4.4%), 14 in 127 (11.0%), and 26 in 271 (9.6%) for femtosecond laser-enabled keratoplasty, Descemet stripping automated endothelial keratoplasty, and conventional penetrating keratoplasty, respectively; 9 femtosecond deep anterior lamellar keratoplasty had no positive results. There was no significant relationship between the types of transplant procedures and the occurrence of positive microbiologic results (P = 0.08). The overall incidence of clinical infection was found to be 0.4% (2 of 569); however, only 1 case (1 of 569 or 0.2%), which was a Candida albicans infection after Descemet stripping automated endothelial keratoplasty, was attributable to the donor. Of 25 cases in which microbiology studies were not performed, none developed a clinical infection. Prevalence of positive microbiologic results and subsequent infections do not appear to be increased with the method of donor handling used for newer techniques for keratoplasty.

  9. Probabilistic brain tissue segmentation in neonatal magnetic resonance imaging.

    Science.gov (United States)

    Anbeek, Petronella; Vincken, Koen L; Groenendaal, Floris; Koeman, Annemieke; van Osch, Matthias J P; van der Grond, Jeroen

    2008-02-01

    A fully automated method has been developed for segmentation of four different structures in the neonatal brain: white matter (WM), central gray matter (CEGM), cortical gray matter (COGM), and cerebrospinal fluid (CSF). The segmentation algorithm is based on information from T2-weighted (T2-w) and inversion recovery (IR) scans. The method uses a K nearest neighbor (KNN) classification technique with features derived from spatial information and voxel intensities. Probabilistic segmentations of each tissue type were generated. By applying thresholds on these probability maps, binary segmentations were obtained. These final segmentations were evaluated by comparison with a gold standard. The sensitivity, specificity, and Dice similarity index (SI) were calculated for quantitative validation of the results. High sensitivity and specificity with respect to the gold standard were reached: sensitivity >0.82 and specificity >0.9 for all tissue types. Tissue volumes were calculated from the binary and probabilistic segmentations. The probabilistic segmentation volumes of all tissue types accurately estimated the gold standard volumes. The KNN approach offers valuable ways for neonatal brain segmentation. The probabilistic outcomes provide a useful tool for accurate volume measurements. The described method is based on routine diagnostic magnetic resonance imaging (MRI) and is suitable for large population studies.

  10. [FREE CROIN FLAP FOR REPAIRING DEFECTS OF DONOR AFTER TOE TISSUE TRANSPLANTATION].

    Science.gov (United States)

    Li, Muwei; Luo Zhaohui; Gu, Hannan; Ma, Lifeng; Yang, Yanjun; Zhang, Ziqing

    2016-02-01

    To discuss the effectiveness of free croin flap in repairing defects of donor after toe or feetissue flap transplantation. Between March 2010 and May 2015, 23 cases of defects of donor after toe or feet tissue flap transplantation were repaired with free croin flap and followed up for more than 6 months, and the clinical data were retrospectively analyzed. There were 15 males and 8 females, with an age range from 17 to 52 years (mean, 25.6 years). All finger or soft tissue defects were caused by trauma. Defects were repaired in emergency operation with toe or feet tissue flap transplantation in 18 cases, defects were secondarily reconstructed at 3-8 months after injury in 5 cases. The defect area at the feet donor site ranged from 3 cmx3 cm to 10 cmx6 cm, all accompanied with exposure of bone, and tendon. The area of free croin flap was 3.5 cm x 3.5 cm-11.0 cm x 6.5 cm, the vessel of flap was anastomosed with artery and vein of foot. The inguinal donor site was sutured directly. The operation time was 3-9 hours (mean, 4.5 hours); the intraoperative blood loss was 50-300 mL (mean, 120 mL). Vessel crisis occurred in 1 case postoperatively; mild and moderate swelling occurred in 3 cases, with small sporadic blisters formation; free croin flap survived completely in the other cases, and primary healing was obtained at feet wound and inguinal donor sites. Twenty-three cases were followed up 6-24 months (mean, 9 months). The color and texture of the croin flaps were similar to that of the adjacent skin, no obvious scar contracture and pigmentation were observed; the patient could walk with weight loading, the two-point discrimination was 18-35 mm (mean, 26 mm) at 6 months after operation. The color, texture, and shape of reconstructed finger was good; the function of grasping and pinching recovered well; the two-point discrimination was 5.5-11.0 mmfunctional evaluation standard by Chinese Medical Association, the results were excellent in 18 cases and good in 5 cases

  11. Microscopy and chemical imaging of Behcet brain tissue

    Science.gov (United States)

    Aranyosiova, Monika; Michalka, Miroslav; Kopani, Martin; Rychly, Boris; Jakubovsky, Jan; Velic, Dusan

    2008-12-01

    Chemical composition and distribution of molecules and elements in a human brain tissue of Behcet diseased patient are of interest. Behcet disease is a multi-system disorder of which pathogenesis and chemical causality are still uncertain. Time-of-flight secondary ion mass spectrometry is used along with scanning electron microscopy and energy dispersive X-ray analysis providing complex composition in Behcet disease and control tissues. Determined organic compounds are represented by fragments of carbohydrates, phospholipids, amino acids, and peptides. The distributions of inorganic species are well represented by heavy trace elements and by oxides in positive and negative polarities of time-of-flight secondary ion mass spectrometry, respectively. Organic and inorganic compounds are qualitatively determined in both samples, Behcet and control, providing complementary chemical images. The complementary chemical images interestingly change with the quantitative regression of organic compounds distribution, characteristic for the healthy control, towards inorganic compounds distribution, characteristic for Behcet tissue.

  12. Arsenic affects inflammatory cytokine expression in Gallus gallus brain tissues.

    Science.gov (United States)

    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 (As2O3)-treated (7.5 mg/kg) group, a middle As2O3-treated (15 mg/kg) group, and a high As2O3-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 As2O3, the levels of inflammatory-related factor NF-κB and pro-inflammatory cytokines in chicken brain tissues increased (P 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.

  13. Diffusion MRI at 25: exploring brain tissue structure and function.

    Science.gov (United States)

    Le Bihan, Denis; Johansen-Berg, Heidi

    2012-06-01

    Diffusion MRI (or dMRI) came into existence in the mid-1980s. During the last 25 years, diffusion MRI has been extraordinarily successful (with more than 300,000 entries on Google Scholar for diffusion MRI). Its main clinical domain of application has been neurological disorders, especially for the management of patients with acute stroke. It is also rapidly becoming a standard for white matter disorders, as diffusion tensor imaging (DTI) can reveal abnormalities in white matter fiber structure and provide outstanding maps of brain connectivity. The ability to visualize anatomical connections between different parts of the brain, non-invasively and on an individual basis, has emerged as a major breakthrough for neurosciences. The driving force of dMRI is to monitor microscopic, natural displacements of water molecules that occur in brain tissues as part of the physical diffusion process. Water molecules are thus used as a probe that can reveal microscopic details about tissue architecture, either normal or in a diseased state. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Role of Stem Cells Transplantation in Tissue Regeneration After Acute or Chronic Acetaminophen Induced Liver Injury.

    Science.gov (United States)

    Katselis, Charalampos; Apostolou, Konstantinos; Feretis, Themistoklis; Papanikolaou, Ioannis G; Zografos, George C; Toutouzas, Konstantinos; Papalois, Apostolos

    2016-01-01

    Acetaminophen-induced liver injury (APAP) is recognized as a frequent etiologic factor responsible for hepatic damage in the developed world. Management remains still elusive as treatment options are limited and their results are inconclusive. Consequently new strategies are explored at the experimental level. Mesenchymal stem cells (MSCs) present a promising modality as they can promote liver regeneration (LG) and compensate acute liver injury (ALI). Our research was focused on articles related to drug-induced liver injury, mechanisms of liver regeneration (LG) after Acute Liver Injury (ALI) and recent experimental protocols of Mesenchymal Stem Cells (MSCs) transplantation after chemical insult. All these studies are cited on Pubmed and MedLine. This review has three distinct sections. First recent developments in ALI pathogenesis are presented. The second section covers cellular pathways and histological findings relevant to liver regeneration. The final chapter analyzes MSCs transplantation protocols after ALI and interrelation between liver regeneration and hepatic differentiation of MSCs. Adipose tissue stem cells (ADSCs) and (MSCs) transplantation represents a promising modality in severe ALI management although many aspects remain to be clarified.

  15. Enhancement of ultraweak photon emission with 3 MHz ultrasonic irradiation on transplanted tumor tissues of mice.

    Science.gov (United States)

    Kim, Hongbae; Ahn, Saeyoung; Kim, Jungdae; Soh, Kwang-Sup

    2008-07-01

    We investigated photon emissions of various bio-samples which were induced by ultrasonic stimulation. It has been reported that ultrasonic stimulations induced the thermal excitation of the bio-tissues. After ultrasonic stimulation, any measurement of photon radiation in the visible spectral range has not been carried out yet. The instruments consisted of electronic devices for an ultrasonic generator of the frequency 3 MHz and a photomultiplier tube (PMT) system counting photons from bio-tissues. The transplanted tumor tissues of mice were prepared for the experiments and their liver and spleen tissues were also used for the controls. It was found that the continuous ultrasonic stimulations with the electrical power 2300 mW induced ultraweak photon emissions from the tumor tissues. The number of induced photon was dependent of the type of the tissues and the stimulation time intervals. The level of photon emission was increased from the mouse tumor exposed to the ultrasonic stimulations, and the changes were discriminated from those of the spleens and livers.

  16. Preliminary study of coconut water for graft tissues preservation in transplantation

    Directory of Open Access Journals (Sweden)

    Jorge Miguel Schettino César

    Full Text Available OBJECTIVE: to verify the effectiveness of coconut water in preserving tissues for transplant. METHODS: Fifty male Wistar rats were randomly distributed in five groups, according to the following preservation solutions for tissue grafts: Group 1: Lactated Ringer; Group 2: Belzer solution; Group 3: mature coconut water; Group 4: green coconut water; Group 5: modified coconut water. In Group 5, the green coconut water has been modified like the Belzer solution. From each animal we harvasted the spleen, ovaries and skin of the back segment. These tissues were preserved for six hours in one of the solutions. Then, the grafts were reimplanted. The recovery of the function of the implanted tissues was assessed 90 days after surgery, by splenic scintigraphy and blood exame. The implanted tissues were collected for histopathological examination. RESULTS: The serum levels did not differ among groups, except for the animals in Group 5, which showed higher levels of IgG than Group 1, and differences in relation to FSH between groups 1 and 2 (p <0.001, 4 and 2 (p = 0.03 and 5 and 2 (p = 0.01. The splenic scintigraphy was not different between groups. The ovarian tissue was better preserved in mature coconut water (p <0.007. CONCLUSION: the coconut water-based solutions preserves spleen, ovary, and rat skin for six hours, maintaining their normal function.

  17. Survival of human mesenchymal stromal cells from bone marrow and adipose tissue after xenogenic transplantation in immunocompetent mice

    DEFF Research Database (Denmark)

    Niemeyer, P; Vohrer, J; Schmal, H

    2008-01-01

    INTRODUCTION: Mesenchymal stromal cells (MSC) represent an attractive cell population for tissue engineering purposes. As MSC are described as immunoprivileged, non-autologous applications seem possible. A basic requirement is the survival of MSC after transplantation in the host. The purpose...... of the current paper was to evaluate the survival of undifferentiated and osteogenically induced human MSC from different origins after transplantation in immunocompetent mice. METHODS: Human MSC were isolated from bone marrow (BMSC) and adipose tissue (ASC). After cultivation on mineralized collagen, MSC were...... transplanted subcutaneously into immunocompetent mice (n=12). Undifferentiated MSC (group A) were compared with osteogenic-induced MSC (group B). Human-specific in situ hybridization and anti-vimentin staining was used to follow MSC after transplantation. Quantitative evaluation of lymphocytes and macrophages...

  18. BIOLOGICAL EFFECTS OF MICROWAVE RADIATION ON BRAIN TISSUE IN RATS

    Directory of Open Access Journals (Sweden)

    Boris Đinđić

    2003-04-01

    Full Text Available Exposure to microwave radiation induces multiple organ dysfunctions, especially in CNS.The aim of this work was investigation of biological effects of microwave radiation on rats' brain and determination of increased oxidative stress as a possible pathogenetic's mechanism.Wis tar rats 3 months old were divided in experimental (4 female and 4 male animal and control group (5 female and 4 male. This experimental group was constantly exposed to a magnetic field of 5 mG. We simulated using of mobile phones 30 min every day. The source of NIR emitted MF that was similar to mobile phones at 900 MHz. The rats were killed after 2 months. Biological effects were determined by observation of individual and collective behavior and body mass changes. Lipid per oxidation was determined by measuring quantity of malondialdehyde (MDA in brain homogenate.The animals in experimental group exposed to EMF showed les weight gain. The most important observations were changing of basic behavior models and expression of aggressive or panic behavior. The content of MDA in brain tissue is singificantly higher (1.42 times in rats exposed to electromagnetic fields (3,82±0.65 vs. control 2.69±0.42 nmol/mg proteins, p<0.01.Increased oxidative stress and lipid peroxidation after exposition in EM fields induced disorders of function and structure of brain.

  19. Improved segmentation of ultrasound brain tissue incorporating expert evaluation.

    Science.gov (United States)

    Vansteenkiste, Ewout; Pizurica, Aleksandra; Philips, Wilfried

    2005-01-01

    The quantitative analysis of medical ultrasound images for the purpose of diagnosis is a difficult task due to the speckle noise present in the images. Nowadays medical doctors depend strongly on the visual interpretation of the images which is subjective to some account. Trying to reduce this noise should assist the experts in a better understanding of some pathologies. We focus on a brain disease called periventricular leukomalacia, also called white matter damage, which occurs frequently on premature neonates. For the moment the affected brain tissue is segmented semi-automatically using two different techniques that take the speckle noise into little account. Here we propose a framework which includes an efficient preprocessing step and relying on expert-based evaluation we develop an integrated segmentation method, which yields a more accurate and better reproducible segmentation.

  20. Histomorphology of the Olfactory Mucosa and Spinal Tissue Sparing Following Transplantation in the Partial Spinal Cord Injury in Rats

    Directory of Open Access Journals (Sweden)

    H Delaviz

    2011-01-01

    Full Text Available Introduction & Objective: Nowadays, cellular and tissues transplant has become the focus of attention for spinal cord injury. It has been shown olfactory nerve cells or olfactory mucosa whi have more efficient on nervous tissue repair and they have been more studied in experimental study. Furthermore, they were used in a few clinical centers for spinal defect. But mucosa tissue and spinal tissue have different structure and there is doubt about the integration of mucosa tissue in nervous tissue. Thus, in this research the morphology and the effect of the fetal olfactory mucosa (FOM on spinal tissue sparing were studied after transplanted into the spinal cord hemisection in rats. Materials & Methods: This experimental study was conducted at Iran University of Medical Sciences in 2008. Of thirty eight female Sprague-Dawley (200-250g rats twenty- eight were spinally hemisected at the L1 spinal level and were randomized into two groups of 14 animals. Treatment group received FOM graft and the control group received fetal respiratory mucosa graft (FRM. The other animals received surgical procedure without spinal cord injury as a sham group. The morphology of the transplant region and spinal tissue sparing was examined histological eight weeks after transplantation. The collected data was analyzed by the SPSS software using ANOVA and the morphology of the transplant region were studied by light microscope. Results: Histological study showed that the both mucosa tissues could not integrate with the parenchyma of the spinal tissue. Although the FOM were fused more than the FRM with the host tissue but clear boundary was seen at the graft–host interface. The mean spinal tissue sparing of the treatment group increased a little compare to the control but a significant difference was not apparent whereas, the spinal tissue sparing in treatment and control groups compare to the sham group decreased significantly (P < 0.05. Conclusion: Transplantation of

  1. Brain Tissue Compartment Density Estimated Using Diffusion-Weighted MRI Yields Tissue Parameters Consistent With Histology

    Science.gov (United States)

    Sepehrband, Farshid; Clark, Kristi A.; Ullmann, Jeremy F.P.; Kurniawan, Nyoman D.; Leanage, Gayeshika; Reutens, David C.; Yang, Zhengyi

    2015-01-01

    We examined whether quantitative density measures of cerebral tissue consistent with histology can be obtained from diffusion magnetic resonance imaging (MRI). By incorporating prior knowledge of myelin and cell membrane densities, absolute tissue density values were estimated from relative intra-cellular and intra-neurite density values obtained from diffusion MRI. The NODDI (neurite orientation distribution and density imaging) technique, which can be applied clinically, was used. Myelin density estimates were compared with the results of electron and light microscopy in ex vivo mouse brain and with published density estimates in a healthy human brain. In ex vivo mouse brain, estimated myelin densities in different sub-regions of the mouse corpus callosum were almost identical to values obtained from electron microscopy (Diffusion MRI: 42±6%, 36±4% and 43±5%; electron microscopy: 41±10%, 36±8% and 44±12% in genu, body and splenium, respectively). In the human brain, good agreement was observed between estimated fiber density measurements and previously reported values based on electron microscopy. Estimated density values were unaffected by crossing fibers. PMID:26096639

  2. Topology-preserving tissue classification of magnetic resonance brain images.

    Science.gov (United States)

    Bazin, Pierre-Louis; Pham, Dzung L

    2007-04-01

    This paper presents a new framework for multiple object segmentation in medical images that respects the topological properties and relationships of structures as given by a template. The technique, known as topology-preserving, anatomy-driven segmentation (TOADS), combines advantages of statistical tissue classification, topology-preserving fast marching methods, and image registration to enforce object-level relationships with little constraint over the geometry. When applied to the problem of brain segmentation, it directly provides a cortical surface with spherical topology while segmenting the main cerebral structures. Validation on simulated and real images characterises the performance of the algorithm with regard to noise, inhomogeneities, and anatomical variations.

  3. Treating Clostridium difficile infections: Should fecal microbiota transplantation be reclassified from investigational drug to human tissue?

    Directory of Open Access Journals (Sweden)

    Mark Stuntz

    2015-10-01

    Full Text Available Fecal microbiota transplantation (FMT has emerged as a highly effective treatment for Clostridium difficile infection (CDI, the most frequent cause of hospital-acquired infectious diarrhea in developed countries and the cause of nearly 30,000 annual deaths in the US. FMT is proving to be more effective at treating CDI than traditional antibacterial therapy, and reduces the exposure of valuable antibiotics to potential resistance. A systematic review to assess the efficacy of FMT for CDI treatment showed that across all studies for recurrent CDI, symptom resolution was observed in 85% of patients. The United States Food and Drug Administration currently classifies FMT as an investigational drug, which imparts overly restrictive regulations that are impossible to apply to FMT in the same manner as conventional drugs. Reclassification of FMT to a human cell, tissue, and cellular and tissue-based product could potentially expand access to this important treatment while maintaining rigorous safety standards.

  4. Coherent control of an opsin in living brain tissue

    Science.gov (United States)

    Paul, Kush; Sengupta, Parijat; Ark, Eugene D.; Tu, Haohua; Zhao, Youbo; Boppart, Stephen A.

    2017-11-01

    Retinal-based opsins are light-sensitive proteins. The photoisomerization reaction of these proteins has been studied outside cellular environments using ultrashort tailored light pulses. However, how living cell functions can be modulated via opsins by modifying fundamental nonlinear optical properties of light interacting with the retinal chromophore has remained largely unexplored. We report the use of chirped ultrashort near-infrared pulses to modulate light-evoked ionic current from Channelrhodopsin-2 (ChR2) in brain tissue, and consequently the firing pattern of neurons, by manipulating the phase of the spectral components of the light. These results confirm that quantum coherence of the retinal-based protein system, even in a living neuron, can influence its current output, and open up the possibilities of using designer-tailored pulses for controlling molecular dynamics of opsins in living tissue to selectively enhance or suppress neuronal function for adaptive feedback-loop applications in the future.

  5. Moving towards in situ tracheal regeneration: the bionic tissue engineered transplantation approach.

    Science.gov (United States)

    Bader, Augustinus; Macchiarini, Paolo

    2010-07-01

    In June 2008, the world's first whole tissue-engineered organ - the windpipe - was successfully transplanted into a 31-year-old lady, and about 18 months following surgery she is leading a near normal life without immunosuppression. This outcome has been achieved by employing three groundbreaking technologies of regenerative medicine: (i) a donor trachea first decellularized using a detergent (without denaturing the collagenous matrix), (ii) the two main autologous tracheal cells, namely mesenchymal stem cell derived cartilage-like cells and epithelial respiratory cells and (iii) a specifically designed bioreactor that reseed, before implantation, the in vitro pre-expanded and pre-differentiated autologous cells on the desired surfaces of the decellularized matrix. Given the long-term safety, efficacy and efforts using such a conventional approach and the potential advantages of regenerative implants to make them available for anyone, we have investigated a novel alternative concept how to fully avoid in vitro cell replication, expansion and differentiation, use the human native site as micro-niche, potentiate the human body's site-specific response by adding boosting, permissive and recruitment impulses in full respect of sociological and regulatory prerequisites. This tissue-engineered approach and ongoing research in airway transplantation is reviewed and presented here.

  6. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient.

    Directory of Open Access Journals (Sweden)

    Ninette Amariglio

    2009-02-01

    Full Text Available BACKGROUND: Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells. METHODS AND FINDINGS: A boy with ataxia telangiectasia (AT was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors. CONCLUSIONS: This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.

  7. Myoglobin Expression in Chelonia mydas Brain, Heart and Liver Tissues

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    RINI PUSPITANINGRUM

    2010-09-01

    Full Text Available An understanding of the underpinning physiology and biochemistry of animals is essential to properly understand the impact of anthropogenic changes and natural catastrophes upon the conservation of endangered species. An observation on the tissue location of the key respiratory protein, myoglobin, now opens up new opportunities for understanding how hypoxia tolerance impacts on diving lifestyle in turtles. The respiratory protein, myoglobin has functions other than oxygen binding which are involved in hypoxia tolerance, including metabolism of reactive oxygen species and of the vascular function by metabolism of nitric oxide. Our work aims to determine whether myoglobin expression in the green turtle exists in multiple non muscle tissues and to confirm the hypothesis that reptiles also have a distributed myoglobin expression which is linked to the hypoxia-tolerant trait. This initial work in turtle hatch Chelonia mydas confirms the presence of myoglobin transcriptin brain, heart and liver tissues. Furthermore, it will serve as a tool for completing the sequence and generating an in situ hybridization probe for verifying of cell location in expressing tissues.

  8. Myoglobin Expression in Chelonia mydas Brain, Heart and Liver Tissues

    Directory of Open Access Journals (Sweden)

    RINI PUSPITANINGRUM

    2010-09-01

    Full Text Available An understanding of the underpinning physiology and biochemistry of animals is essential to properly understand the impact of anthropogenic changes and natural catastrophes upon the conservation of endangered species. An observation on the tissue location of the key respiratory protein, myoglobin, now opens up new opportunities for understanding how hypoxia tolerance impacts on diving lifestyle in turtles. The respiratory protein, myoglobin has functions other than oxygen binding which are involved in hypoxia tolerance, including metabolism of reactive oxygen species and of the vascular function by metabolism of nitric oxide. Our work aims to determine whether myoglobin expression in the green turtle exists in multiple non muscle tissues and to confirm the hypothesis that reptiles also have a distributed myoglobin expression which is linked to the hypoxiatolerant trait. This initial work in turtle hatch Chelonia mydas confirms the presence of myoglobin transcriptin brain, heart and liver tissues. Furthermore, it will serve as a tool for completing the sequence and generating an in situ hybridization probe for verifying of cell location in expressing tissues.

  9. State-of-the-Art Methods for Brain Tissue Segmentation: A Review.

    Science.gov (United States)

    Dora, Lingraj; Agrawal, Sanjay; Panda, Rutuparna; Abraham, Ajith

    2017-01-01

    Brain tissue segmentation is one of the most sought after research areas in medical image processing. It provides detailed quantitative brain analysis for accurate disease diagnosis, detection, and classification of abnormalities. It plays an essential role in discriminating healthy tissues from lesion tissues. Therefore, accurate disease diagnosis and treatment planning depend merely on the performance of the segmentation method used. In this review, we have studied the recent advances in brain tissue segmentation methods and their state-of-the-art in neuroscience research. The review also highlights the major challenges faced during tissue segmentation of the brain. An effective comparison is made among state-of-the-art brain tissue segmentation methods. Moreover, a study of some of the validation measures to evaluate different segmentation methods is also discussed. The brain tissue segmentation, content in terms of methodologies, and experiments presented in this review are encouraging enough to attract researchers working in this field.

  10. External ventricular drain causes brain tissue damage: an imaging study.

    Science.gov (United States)

    Ortolano, Fabrizio; Carbonara, Marco; Stanco, Antonella; Civelli, Vittorio; Carrabba, Giorgio; Zoerle, Tommaso; Stocchetti, Nino

    2017-10-01

    An external ventricular drain (EVD) is used to measure intracranial pressure (ICP) and to drain cerebrospinal fluid (CSF). The procedure is generally safe, but parenchymal sequelae are reported as a possible side effect, with variable incidence. We investigated the mechanical sequelae of EVD insertion and their clinical significance in acute brain-injured patients, with a special focus on hemorrhagic lesions. Mechanical sequelae of EVD insertion were detected in patients by computed tomography (CT) and magnetic resonance imaging (MRI), performed for clinical purposes. In 155 patients we studied the brain tissue surrounding the EVD by CT scan (all patients) and MRI (16 patients); 53 patients were studied at three time points (day 1-2, day 3-10, >10 days after EVD placement) to document the lesion time course. Small hemorrhages, with a hyperdense core surrounded by a hypodense area, were identified by CT scan in 33 patients. The initial average (hyper- + hypodense) lesion volume was 8.16 ml, increasing up to 15 ml by >10 days after EVD insertion. These lesions were not accompanied by neurologic deterioration or ICP elevation. History of arterial hypertension, coagulation abnormalities and multiple EVD insertions were significantly associated with hemorrhages. In 122 non-hemorrhagic patients, we detected very small hypodense areas (average volume 0.38 ml) surrounding the catheter. At later times these hypodensities slightly increased. MRI studies in 16 patients identified both intra- and extracellular edema around the catheters. The extracellular component increased with time. EVD insertion, even when there are no clinically important complications, causes a tissue reaction with minimal bleedings and small areas of brain edema.

  11. Neural stem cell transplantation in an animal model of traumatic brain injury.

    Science.gov (United States)

    Thomaidou, Dimitra

    2014-01-01

    The central nervous system (CNS) can be damaged by a wide range of conditions resulting in loss of specific populations of neurons and/or glial cells and in the development of defined psychiatric or neurological symptoms of varying severity. As the CNS has limited inherent capacity to regenerate lost tissue and self-repair, the development of therapeutic strategies for the treatment of CNS insults remains a serious scientific challenge with potential important clinical applications. In this context, strategies involving transplantation of specific cell populations, such as stem cells and neural stem cells (NSCs), to replace damaged cells offers an opportunity for the development of cell-based therapies. Along these lines, in this review we describe a protocol which involves transplantation of NPCs, genetically engineered to overexpress the neurogenic molecule Cend1 and have thus the potency to differentiate with higher frequency towards the neuronal lineage in a rodent model of stab wound cortical injury.

  12. The critical apical diameter to obtain regeneration of the pulp tissue after tooth transplantation, replantation, or regenerative endodontic treatment.

    Science.gov (United States)

    Laureys, Wim G M; Cuvelier, Claude A; Dermaut, Luc R; De Pauw, Guy A M

    2013-06-01

    Regeneration of pulp-like tissue in the pulp chamber after tooth transplantation, replantation, or in regenerative endodontic treatment is only possible if the apical foramen is open. According to the literature, the success of regeneration decreases considerably if the foramen is smaller than 1 mm when measured on radiographs. The aim of this study was to study histologically the relation between the width of the apical foramen and regeneration of tissue in the pulp chamber after autotransplantation. Fifteen single-rooted mature teeth of 3 adult beagle dogs were used. All experimental teeth were extracted and underwent apicoectomy. The teeth were photographed from the apical side, and the width of the foramen was calculated. The foramen width ranged from 0.24-1.09 mm. All teeth were replanted in infraocclusion. The observation period was 90 days after transplantation. The 10 teeth with the smallest apical diameter, ranging between 0.24 and 0.53 mm, showed vital tissue in at least one third of the pulp chamber. The 6 most successful teeth showing vital tissue in the entire pulp chamber had an apical diameter between 0.32 and 0.65 mm, and 80% of the experimental teeth with a diameter varying between 1.09 and 0.31 mm showed vital tissue in at least one third of the pulp chamber 90 days after transplantation. The size of the apical foramen seems not to be the all decisive factor for successful revascularization and ingrowth of new tissue after transplantation. The minimum width of the apical foramen has not been determined, but a size smaller than 1 mm does not prevent revascularization and ingrowth of vital tissue. In this animal study an apical foramen of 0.32 mm did not prevent ingrowth of new tissue in two-thirds of the pulp chamber 90 days after transplantation. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  13. Further Controversies About Brain Tissue Oxygenation Pressure-Reactivity After Traumatic Brain Injury

    DEFF Research Database (Denmark)

    Andresen, Morten; Donnelly, Joseph; Aries, Marcel

    2017-01-01

    arterial pressure and intracranial pressure. A new ORx index based on brain tissue oxygenation and cerebral perfusion pressure (CPP) has been proposed that similarly allows for evaluation of cerebrovascular reactivity. Conflicting results exist concerning its clinical utility. METHODS: Retrospective....... Higher mortality related to average CPP regardless of which index was used to calculate CPPopt. CONCLUSION: In the TBI setting, ORx does not appear to correlate with vascular pressure reactivity as assessed with PRx. Its potential use for individualizing CPP thresholds remains unclear....

  14. Hallmarks of Alzheimer's Disease in Stem-Cell-Derived Human Neurons Transplanted into Mouse Brain.

    Science.gov (United States)

    Espuny-Camacho, Ira; Arranz, Amaia M; Fiers, Mark; Snellinx, An; Ando, Kunie; Munck, Sebastian; Bonnefont, Jerome; Lambot, Laurie; Corthout, Nikky; Omodho, Lorna; Vanden Eynden, Elke; Radaelli, Enrico; Tesseur, Ina; Wray, Selina; Ebneth, Andreas; Hardy, John; Leroy, Karelle; Brion, Jean-Pierre; Vanderhaeghen, Pierre; De Strooper, Bart

    2017-03-08

    Human pluripotent stem cells (PSCs) provide a unique entry to study species-specific aspects of human disorders such as Alzheimer's disease (AD). However, in vitro culture of neurons deprives them of their natural environment. Here we transplanted human PSC-derived cortical neuronal precursors into the brain of a murine AD model. Human neurons differentiate and integrate into the brain, express 3R/4R Tau splice forms, show abnormal phosphorylation and conformational Tau changes, and undergo neurodegeneration. Remarkably, cell death was dissociated from tangle formation in this natural 3D model of AD. Using genome-wide expression analysis, we observed upregulation of genes involved in myelination and downregulation of genes related to memory and cognition, synaptic transmission, and neuron projection. This novel chimeric model for AD displays human-specific pathological features and allows the analysis of different genetic backgrounds and mutations during the course of the disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Transplantation of Cultivated Fibroblasts on a Backing of Xenogenic Tissue in the Treatment of Wounds

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    Kabylbek Abugaliyev

    2014-12-01

    Full Text Available Introduction. Trophic ulcers are a common health problem, and there are numerous treatment methods. Irreversible damage in the skin, subcutaneous tissue, and fascia with long-term ulcer existence make standard autotransplantation inneffective. Skin grafts are often complicated by partial or complete rejection of skin flaps. The aim of this study was to examine the feasibility of using transplanted cultivated allogenic fibroblasts on the backing of a cellularless xenogenic fabric for wound healing.Methods. Transplantation of cultured embryonic fibroblasts on a backing of xenogenic tissue was used in the complex treatment of trophic ulcers for stimulation of regenerative processes. Decellularization xenogenic film was previously held. Then allogenic fibroblasts were cultivated on the surface of collagen-elastin matrix. Since 2013, we treated 12 patients with giant ulcers caused by the following: lymphedema (2 patients, vascular disease (3 patients, diabetes (2 patients, after injury (4 patients, and radiation ulcer (1 patient. Dimensions of ulcers were from 150 to 600 cm2. Duration of the lower limb ulcers ranged from 8 months to 10 years. For a number of years, all patients were on a complex therapy, which had not resulted in healing wounds. During the operation when excision of granulation tissue was performed, plastic wounds perforated with the ratio 1:2 autoskin. Xenogenic fabric with cultured fibroblasts was applied on top. In this case, xenogenic film protected the skin from drying, created optimal microclimate, and cultured fibroblasts stimulating regeneration and improving engraftment.Results. The first redress was held on the fifth day. In all cases, the results of engraftment skin grafts achieved maximum possible (100% and optimal (90%. Complete epithelialization of the cell perforation was seen in five patients on the fifth day and three on seventh day after skin plastics. Average period of inpatient treatment was 20.7 days. All

  16. Co-transplantation of syngeneic mesenchymal stem cells improves survival of allogeneic glial-restricted precursors in mouse brain.

    Science.gov (United States)

    Srivastava, Amit K; Bulte, Camille A; Shats, Irina; Walczak, Piotr; Bulte, Jeff W M

    2016-01-01

    Loss of functional cells from immunorejection during the early post-transplantation period is an important factor that reduces the efficacy of stem cell-based therapies. Recent studies have shown that transplanted mesenchymal stem cells (MSCs) can exert therapeutic effects by secreting anti-inflammatory and pro-survival trophic factors. We investigated whether co-transplantation of MSCs could improve the survival of other transplanted therapeutic cells. Allogeneic glial-restricted precursors (GRPs) were isolated from the brain of a firefly luciferase transgenic FVB mouse (at E13.5 stage) and intracerebrally transplanted, either alone, or together with syngeneic MSCs in immunocompetent BALB/c mice (n=20) or immunodeficient Rag2(-/-) mice as survival control (n=8). No immunosuppressive drug was given to any animal. Using bioluminescence imaging (BLI) as a non-invasive readout of cell survival, we found that co-transplantation of MSCs significantly improved (ptransplanted cells surviving in both the GRP only and the GRP+MSC group. In contrast, on day 21 post-transplantation, we observed a 94.2% decrease in BLI signal intensity in immunocompetent mice transplanted with GRPs alone versus 68.1% in immunocompetent mice co-transplanted with MSCs and GRPs (pcells, reduced astrogliosis, and a higher number of FoxP3(+) cells at the site of transplantation for the immunocompetent mice receiving MSCs. The present study demonstrates that co-transplantation of MSCs can be used to create a microenvironment that is more conducive to the survival of allogeneic GRPs. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Photoreceptor protection by iris pigment epithelial transplantation transduced with AAV-mediated brain-derived neurotrophic factor gene.

    Science.gov (United States)

    Hojo, Masayoshi; Abe, Toshiaki; Sugano, Eriko; Yoshioka, Yuki; Saigo, Yoko; Tomita, Hiroshi; Wakusawa, Ryosuke; Tamai, Makoto

    2004-10-01

    To determine whether subretinal transplantation of iris pigment epithelial (IPE) cells transduced with the adeno-associated virus (AAV2)-mediated brain-derived neurotrophic factor (BDNF) gene can protect photoreceptors against phototoxicity. The BDNF gene was inserted into AAV2 (AAV2-BDNF), and the recombinant AAV2 was transduced into rat IPE (AAV2-BDNF-IPE) cells at various multiplicities of infection (MOI). The concentrations of AAV capsids and BDNF were determined by enzyme-linked immunosorbent assay (ELISA). The AAV2-BDNF-IPE cells were transplanted into the subretinal space of rats, and the rats were placed under constant light on days 1 and 90 after the transplantation. The thickness of the outer nuclear layer was measured in histologic sections and compared to that of control sections. The expression of beta-galactosidase (LacZ) in the subretinal space was confirmed by LacZ staining after AAV2-LacZ-IPE transplantation. BDNF gene expression after transplantation was confirmed by real-time polymerase chain reaction (PCR). Transduction efficiency increased with successive days in culture and increased with higher MOI in vitro. The expression of the BDNF gene in the subretinal space was higher in AAV-BDNF-IPE than with AAV2-LacZ-IPE or with IPE-only transplantation. LacZ expression was observed in the subretinal space 7 and 90 days after transplantation. A statistically significant photoreceptor protection was observed on days 1 and 90 in eyes receiving the AAV2-BDNF-IPE transplant, in both the superior transplant site and the inferior hemispheres which did not receive the transplant. Transplantation of AAV2-BDNF-IPE cells may be an alternative method of delivering neurotrophic factors to the lesion.

  18. Cytological features of live limbal tissue donor eyes for autograft or allograft limbal stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Jeison de Nadai Barros

    2011-08-01

    Full Text Available PURPOSE: To evaluate by impression cytology (IC the corneal surface of live limbal tissue donor eyes for autograft or allograft limbal stem cell transplantation (LSCT. METHODS: Twenty limbal donors were enrolled (17 for autograft LSCT and 3 for allograft. Impression cytology was performed before transplantation of superior and inferior limbal grafts and after the third postoperative month. RESULTS: Impression cytology analysis showed sheets of corneal epithelial cells and goblet cell absence beyond the edge of the keratectomy sites in all patients, suggesting that conjunctival invasion towards the center did not occur in any eye. Partial conjunctivalization within 2 to 3 clock hours, confirmed by the presence of goblet cells, was limited to the keratectomy site in 10% of the cases. CONCLUSION: A clear central corneal surface was demonstrated in all eyes following surgery leading to the conclusion that limbal donation was a safe procedure in this group of patients. A small percentage of eyes can have donor sites re-epithelized with conjunctival cells at the periphery of the cornea.

  19. Laboratorial evaluation of potential donors of organs and tissues for transplantation

    Directory of Open Access Journals (Sweden)

    Quinidia Lúcia Duarte de Almeida Quithé de Vasconcelos

    2014-06-01

    Full Text Available The objective of this study was to describe the laboratorial complementary evaluation in potential donors of organs and tissues for transplantation. It is a descriptive, quantitative study made in six hospitals in Natal/ Rio Grande do Norte, Brazil, between August/2010 to February/2011. The sample consisted of 65 potential donors and a checklist type instrument was used. Information was collected and analyzed using descriptive statistics. From a total number of donors, 89.2% had blood typing, 80.0% hematological tests and verification of the electrolytes. As for the functions, 70.8% had tests for verification of pulmonary function and 80.0% for renal function. From the alterations detected, 69.2% presented hyperoxia, 66.2% leukocytosis, 47.7% hypernatremia, 43.1% increase in the creatine kinase, 10.0% with positive serology. Relevant tests were not made. It is essential to assess potential donors to detect and treat alterations, ensuring the quality of the organs and the quality of the transplantation.

  20. Subcutaneous ovarian tissue transplantation in nonhuman primates: duration of endocrine function and normalcy of subsequent offspring as demonstrated by reproductive competence, oocyte production, and telomere length.

    Science.gov (United States)

    Lee, David M; Thomas, Carrie M; Xu, Fuhua; Yeoman, Richard R; Xu, Jing; Stouffer, Richard L; Wolf, Don P; Zelinski, Mary B

    2017-09-23

    The main purposes of the study were to investigate the endocrine function of ovarian tissue transplanted to heterotopic subcutaneous sites and the reproductive competence and telomere length of a nonhuman primate originating from transplanted tissue. Ovarian cortex pieces were transplanted into the original rhesus macaques in the arm subcutaneously, in the abdomen next to muscles, or in the kidney. Serum estradiol (E2) and progesterone (P4) concentrations were measured weekly for up to 8 years following tissue transplantation. A monkey derived from an oocyte in transplanted ovarian tissue entered time-mated breeding and underwent controlled ovarian stimulation. Pregnancy and offspring were evaluated. Telomere lengths and oocytes obtained following controlled ovarian stimulation were assessed. Monkeys with transplants in the arm and abdomen had cyclic E2 of 100 pg/ml, while an animal with arm transplants had E2 of 50 pg/ml. One monkey with transplants in the abdomen and kidney had ovulatory cycles for 3 years. A monkey derived from an oocyte in transplanted tissue conceived and had a normal gestation until intrapartum fetal demise. She conceived again and delivered a healthy offspring at term. Controlled ovarian stimulations of this monkey yielded mature oocytes comparable to controls. Her telomere length was long relative to controls. Heterotopic ovarian tissue transplants yielded long-term endocrine function in macaques. A monkey derived from an oocyte in transplanted tissue was reproductively competent. Her telomere length did not show epigenetically induced premature cellular aging. Ovarian tissue transplantation to heterotopic sites for fertility preservation should move forward cautiously, yet optimistically.

  1. Influence of the extracellular matrix on endogenous and transplanted stem cells after brain damage

    Science.gov (United States)

    Roll, Lars; Faissner, Andreas

    2014-01-01

    The limited regeneration capacity of the adult central nervous system (CNS) requires strategies to improve recovery of patients. In this context, the interaction of endogenous as well as transplanted stem cells with their environment is crucial. An understanding of the molecular mechanisms could help to improve regeneration by targeted manipulation. In the course of reactive gliosis, astrocytes upregulate Glial fibrillary acidic protein (GFAP) and start, in many cases, to proliferate. Beside GFAP, subpopulations of these astroglial cells coexpress neural progenitor markers like Nestin. Although cells express these markers, the proportion of cells that eventually give rise to neurons is limited in many cases in vivo compared to the situation in vitro. In the first section, we present the characteristics of endogenous progenitor-like cells and discuss the differences in their neurogenic potential in vitro and in vivo. As the environment plays an important role for survival, proliferation, migration, and other processes, the second section of the review describes changes in the extracellular matrix (ECM), a complex network that contains numerous signaling molecules. It appears that signals in the damaged CNS lead to an activation and de-differentiation of astrocytes, but do not effectively promote neuronal differentiation of these cells. Factors that influence stem cells during development are upregulated in the damaged brain as part of an environment resembling a stem cell niche. We give a general description of the ECM composition, with focus on stem cell-associated factors like the glycoprotein Tenascin-C (TN-C). Stem cell transplantation is considered as potential treatment strategy. Interaction of transplanted stem cells with the host environment is critical for the outcome of stem cell-based therapies. Possible mechanisms involving the ECM by which transplanted stem cells might improve recovery are discussed in the last section. PMID:25191223

  2. Longitudinal intrinsic brain activity changes in cirrhotic patients before and one month after liver transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Yue; Huang, Li Xiang; Xie, Shuang [Dept. of Radiology, Tianjin First Central Hospital, Tianjin (China); and others

    2017-04-15

    To evaluate the spontaneous brain activity alterations in liver transplantation (LT) recipients using resting-state functional MRI. Twenty cirrhotic patients as transplant candidates and 25 healthy controls (HCs) were included in this study. All patients repeated the MRI study one month after LT. Amplitude of low-frequency fluctuation (ALFF) values were compared between cirrhotic patients (both pre- and post-LT) and HCs as well as between the pre- and post-LT groups. The relationship between ALFF changes and venous blood ammonia levels and neuropsychological tests were investigated using Pearson's correlation analysis. In the cirrhotic patients, decreased ALFF in the vision-related regions (left lingual gyrus and calcarine), sensorimotor-related regions (left postcentral gyrus and middle cingulate cortex), and the default-mode network (bilateral precuneus and left inferior parietal lobule) were restored, and the increased ALFF in the temporal and frontal lobe improved in the early period after LT. The ALFF decreases persisted in the right supplementary motor area, inferior parietal lobule, and calcarine. The ALFF changes in the right precuneus were negatively correlated with changes in number connection test-A scores (r = 0.507, p < 0.05). LT improved spontaneous brain activity and the results for associated cognition tests. However, decreased ALFF in some areas persisted, and new-onset abnormal ALFF were possible, indicating that complete cognitive function recovery may need more time.

  3. Intracerebral adult stem cells transplantation increases brain-derived neurotrophic factor levels and protects against phencyclidine-induced social deficit in mice

    Science.gov (United States)

    Barzilay, R; Ben-Zur, T; Sadan, O; Bren, Z; Taler, M; Lev, N; Tarasenko, I; Uzan, R; Gil-Ad, I; Melamed, E; Weizman, A; Offen, D

    2011-01-01

    Stem cell-based regenerative therapy is considered a promising cellular therapeutic approach for the patients with incurable brain diseases. Mesenchymal stem cells (MSCs) represent an attractive cell source for regenerative medicine strategies for the treatment of the diseased brain. Previous studies have shown that these cells improve behavioral deficits in animal models of neurological disorders such as Parkinson's and Huntington's diseases. In the current study, we examined the capability of intracerebral human MSCs transplantation (medial pre-frontal cortex) to prevent the social impairment displayed by mice after withdrawal from daily phencyclidine (PCP) administration (10 mg kg−1 daily for 14 days). Our results show that MSCs transplantation significantly prevented the PCP-induced social deficit, as assessed by the social preference test. In contrast, the PCP-induced social impairment was not modified by daily clozapine treatment. Tissue analysis revealed that the human MSCs survived in the mouse brain throughout the course of the experiment (23 days). Significantly increased cortical brain-derived neurotrophic factor levels were observed in the MSCs-treated group as compared with sham-operated controls. Furthermore, western blot analysis revealed that the ratio of phosphorylated Akt to Akt was significantly elevated in the MSCs-treated mice compared with the sham controls. Our results demonstrate that intracerebral transplantation of MSCs is beneficial in attenuating the social deficits induced by sub-chronic PCP administration. We suggest a novel therapeutic approach for the treatment of schizophrenia-like negative symptoms in animal models of the disorder. PMID:22832353

  4. Brain Tissue Oxygen: In Vivo Monitoring with Carbon Paste Electrodes

    Directory of Open Access Journals (Sweden)

    John P. Lowry

    2005-11-01

    Full Text Available In this communication we review selected experiments involving the use ofcarbon paste electrodes (CPEs to monitor and measure brain tissue O2 levels in awakefreely-moving animals. Simultaneous measurements of rCBF were performed using the H2clearance technique. Voltammetric techniques used include both differential pulse (O2 andconstant potential amperometry (rCBF. Mild hypoxia and hyperoxia produced rapidchanges (decrease and increase respectively in the in vivo O2 signal. Neuronal activation(tail pinch and stimulated grooming produced similar increases in both O2 and rCBFindicating that CPE O2 currents provide an index of increases in rCBF when such increasesexceed O2 utilization. Saline injection produced a transient increase in the O2 signal whilechloral hydrate produced slower more long-lasting changes that accompanied the behavioralchanges associated with anaesthesia. Acetazolamide increased O2 levels through an increasein rCBF.

  5. Magnetic Resonance Imaging of Cardiac Strain Pattern Following Transplantation of Human Tissue Engineered Heart Muscles

    Science.gov (United States)

    Qin, Xulei; Riegler, Johannes; Tiburcy, Malte; Zhao, Xin; Chour, Tony; Ndoye, Babacar; Nguyen, Michael; Adams, Jackson; Ameen, Mohamed; Denney, Thomas S.; Yang, Phillip C.; Nguyen, Patricia; Zimmermann, Wolfram H.; Wu, Joseph C.

    2017-01-01

    Background The use of tissue engineering approaches in combination with exogenously produced cardiomyocytes offers the potential to restore contractile function after myocardial injury. However, current techniques assessing changes in global cardiac performance following such treatments are plagued by relatively low detection ability. As the treatment is locally performed, this detection could be improved by myocardial strain imaging that measures regional contractility. Methods and Results Tissue engineered heart muscles (EHMs) were generated by casting human embryonic stem cell-derived cardiomyocytes with collagen in preformed molds. EHMs were transplanted (n=12) to cover infarct and border zones of recipient rat hearts one month after ischemia reperfusion injury. A control group (n=10) received only sham placement of sutures without EHMs. To assess the efficacy of EHMs, MRI and ultrasound-based strain imaging were performed prior to and four weeks after transplantation. In addition to strain imaging, global cardiac performance was estimated from cardiac MRI. Although no significant differences were found with global changes in left ventricular ejection fraction (EF) (Control −9.6±1.3% vs. EHM −6.2±1.9%, P=0.17), regional myocardial strain from tagged MRI was able to detect preserved systolic function in EHM-treated animals compared to control (Control 4.4±1.0% vs. EHM 1.0±0.6%, P=0.04). However, ultrasound-based strain failed to detect any significant change (Control 2.1±3.0% vs. EHM 6.3±2.9%, P=0.46). Conclusions This study highlights the feasibility of using cardiac strain from tagged MRI to assess functional changes in rat models due to localized regenerative therapies, which may not be detected by conventional measures of global systolic performance. PMID:27903535

  6. Real-time changes in brain tissue oxygen during endovascular treatment of cerebral vasospasm

    DEFF Research Database (Denmark)

    Rasmussen, Rune; Bache, Søren; Stavngaard, Trine

    2015-01-01

    minute-by-minute changes in brain tissue oxygen during balloon angioplasty and intraarterial administration of vasodilators in three patients.Our results confirm that endovascular intervention is capable of not only resolving angiographic vasospasm, but also of normalizing values of brain tissue oxygen...... pressure (PtiO₂) in target parenchyma. However, during the intervention, dangerously low levels of brain tissue oxygen, leading to cerebral infarction, may occur. Thus, no clinical improvement was seen in two of the patients and a dramatic worsening was observed in the third patient. Because the decrease...... in brain tissue oxygen was seen after administration of vasopressor agents, this may be a contributing factor....

  7. Discriminating healthy from tumor and necrosis tissue in rat brain tissue samples by Raman spectral imaging.

    Science.gov (United States)

    Amharref, Nadia; Beljebbar, Abdelilah; Dukic, Sylvain; Venteo, Lydie; Schneider, Laurence; Pluot, Michel; Manfait, Michel

    2007-10-01

    The purpose of this study was to investigate molecular changes associated with glioma tissues by Raman microspectroscopy in order to develop its use in clinical practice. Spectroscopic markers obtained from C6 glioma tissues were compared to conventional histological and histochemical techniques. Cholesterol and phospholipid contents were highest in corpus callosum and decreased gradually towards the cortex surface as well as in the tumor. Two different necrotic areas have been identified: a fully necrotic zone characterized by the presence of plasma proteins and a peri-necrotic area with a high lipid content. This result was confirmed by Nile Red staining. Additionally, one structure was detected in the periphery of the tumor. Invisible with histopathological hematoxylin and eosin staining, it was revealed by immunohistochemical Ki-67 and MT1-MMP staining used to visualize the proliferative and invasive activities of glioma, respectively. Hierarchical cluster analysis on the only cluster averaged spectra showed a clear distinction between normal, tumoral, necrotic and edematous tissues. Raman microspectroscopy can discriminate between healthy and tumoral brain tissue and yield spectroscopic markers associated with the proliferative and invasive properties of glioblastoma. Development of in vivo Raman spectroscopy could thus accurately define tumor margins, identify tumor remnants, and help in the development of novel therapies for glioblastoma.

  8. MALDI mass spectrometry based molecular phenotyping of CNS glial cells for prediction in mammalian brain tissue

    DEFF Research Database (Denmark)

    Hanrieder, Jørg; Wicher, Grzegorz; Bergquist, Jonas

    2011-01-01

    tracers for prediction of oligodendroglial and astroglial localization in brain tissue. The different cell type specific protein distributions in tissue were validated using immunohistochemistry. ICMS of intact neuroglia is a simple and straightforward approach for characterization and discrimination...

  9. Registry of Hospital das Clínicas of the University of São Paulo Medical School: first official solid organ and tissue transplantation report - 2008

    Directory of Open Access Journals (Sweden)

    Estela Azeka

    2009-02-01

    Full Text Available OBJECTIVE: The aim of this study was to report a single center experience of organ and tissue transplantation INTRODUCTION: This is the first report of organ and tissue transplantation at the Hospital das Clínicas of the University of Sao Paulo Medical School. METHODS: We collected data from each type of organ transplantation from 2002 to 2007. The data collected were patient characteristics and actuarial survival Kaplan-Meier curves at 30 days, one year, and five years RESULTS: There were a total of 3,321 transplants at our institution and the 5-year survival curve ranged from 53% to 88%. CONCLUSION: This report shows that solid organ and tissue transplants are feasible within the institution and allow us to expect that the quality of transplantation will improve in the future.

  10. Transplantation of artificial human lymphatic vascular tissues fabricated using a cell-accumulation technique and their engraftment in mouse tissue with vascular remodeling.

    Science.gov (United States)

    Asano, Yoshiya; Shimoda, Hiroshi; Matsusaki, Michiya; Akashi, Mitsuru

    2017-09-06

    Transplantation of engineered tissues with microvascular structure is advancing towards therapeutic application to improve the flow of blood and/or lymphatic fluids. In lymphatic disorders, transplantation of tissue-engineered lymphatic grafts can be an ideal treatment for draining excessive lymphatic fluid. In this study, we examined the transplantation of three-dimensional artificial human lymphatic network tissue (AHLT) fabricated by the cell accumulation technique into the subcutaneous tissue and fascia of mice. At 2 weeks after transplantation, the AHLT showed engraftment of artificial lymphatic vessels immunopositive for human CD31 and human podoplanin. Notably, we also observed the generation of blood vessel-like structure comprising endothelial cells immunopositive for human CD34 and mural-like cells immunopositive for human CD90 and αSMA, which were considered as myofibroblasts. In the fabrication of AHLT in vitro, the sporadic emergence of human CD34-positive / Prox-1-negative sites was observed, followed by the formation of blood vessel-like structure in the graft within 7 days after transplantation. The fine structure of engrafted AHLT observed by transmission electron microscopy showed that the engrafted artificial lymphatic vessels possess the specific structures of native lymphatic capillaries such as loose inter-endothelial connections and anchoring filaments. In contrast, blood vessel-like structure showed tight inter-endothelial connections, thick basement membranes, and layers of mural-like cells, which resemble small blood vessels. These results suggested the remodeling of artificial lymphatic network to form blood vessel-like structure associated with mural-like cells along with AHLT fabrication and engraftment. This article is protected by copyright. All rights reserved.

  11. Transplantation of Xenopus laevis tissues to determine the ability of motor neurons to acquire a novel target.

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    Karen L Elliott

    Full Text Available The evolutionary origin of novelties is a central problem in biology. At a cellular level this requires, for example, molecularly resolving how brainstem motor neurons change their innervation target from muscle fibers (branchial motor neurons to neural crest-derived ganglia (visceral motor neurons or ear-derived hair cells (inner ear and lateral line efferent neurons. Transplantation of various tissues into the path of motor neuron axons could determine the ability of any motor neuron to innervate a novel target. Several tissues that receive direct, indirect, or no motor innervation were transplanted into the path of different motor neuron populations in Xenopus laevis embryos. Ears, somites, hearts, and lungs were transplanted to the orbit, replacing the eye. Jaw and eye muscle were transplanted to the trunk, replacing a somite. Applications of lipophilic dyes and immunohistochemistry to reveal motor neuron axon terminals were used. The ear, but not somite-derived muscle, heart, or liver, received motor neuron axons via the oculomotor or trochlear nerves. Somite-derived muscle tissue was innervated, likely by the hypoglossal nerve, when replacing the ear. In contrast to our previous report on ear innervation by spinal motor neurons, none of the tissues (eye or jaw muscle was innervated when transplanted to the trunk. Taken together, these results suggest that there is some plasticity inherent to motor innervation, but not every motor neuron can become an efferent to any target that normally receives motor input. The only tissue among our samples that can be innervated by all motor neurons tested is the ear. We suggest some possible, testable molecular suggestions for this apparent uniqueness.

  12. Ectopic Brain Tissue in a Child: A Case Report A Case of Ectopic Brain Tissue in the Nasophaynx in Thailand

    Directory of Open Access Journals (Sweden)

    Vannipa Vathanophas

    2017-03-01

    Full Text Available Brain heterotopia is a benign tumor composed of differentiated neural tissue that is located outside the cranial vault. This condition is uncommon and presents as a congenital pharyngeal mass. Here, we report a case of neuroepithelial heterotopia in the nasopharyngeal area of a six-month-old boy who presented with cleft palate and stridor. The tumor demonstrated aggressive growth with oropharyngeal involvement. Radiologic finding revealed a large heterogeneous enhancement on the left side of the nasopharynx, involving the uvula, left lateral pharyngeal wall, and left tonsil. No connection to the brain or spinal cord was apparent on imaging. Histologic features included presence of neuroglial heterotopias, composed predominately of glial cells in a surrounding neurofibrillary matrix. Surgery was the selected intervention, with wide excision performed via cleft palate. Previously published literature relevant to this case were reviewed and discussed. Recurrence is common in incomplete resection, although there was no evidence of recurrence at the two-year follow-up in this patient.

  13. Neuroprotective Effects of Bone Marrow Stromal Cell Transplantation in Combination With Treadmill Exercise Following Traumatic Brain Injury.

    Science.gov (United States)

    Shin, Mal Soon; Park, Hun Kyung; Kim, Tae Woon; Ji, Eun Sang; Lee, Jae Min; Choi, Han Sung; Kim, Mi Ye; Kim, Young Pyo

    2016-05-01

    Traumatic brain injury (TBI) causes cognitive impairments, motor deficits, and neuropsychiatric/behavioral deficits problems. Transplantation of bone marrow stromal cells (BMSCs) facilitates functional recovery from brain insults. Treadmill exercise increases neurogenesis and inhibits apoptosis. In this study, we investigated the effects of BMSC transplantation in combination with treadmill exercise on memory function, by evaluating its effect on neurogenesis and apoptosis in the hippocampus following TBI. TBI was induced using an electromagnetic-controlled cortical impact device. BMSCs were transplanted into both sides of traumatic scar region 1 week after TBI induction. One week after transplantation of BMSCs, the rats in the exercise groups were trained to run on a treadmill for 30 minutes once daily for 28 days. Step-down avoidance task and radial 8-arm maze test were conducted. Levels of 5-bromo-2ʹ-deoxyuridine and caspase-3 were evaluated using immunohistochemistry. Western blot was used to evaluate the expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), total-extracellular signal-regulated kinase 1 and 2 (t-ERK1/2), phosphorylated-ERK1/2 (p-ERK1/2), Bcl-2, and Bax. TBI deteriorated memory function, suppressed neurogenesis, and accelerated apoptosis in the hippocampus. Treadmill exercise and BMSC transplantation independently improved memory function by increasing neurogenesis with suppression of apoptosis through the BDNF-ERK pathway in the TBI-induced rats. Combination of BMSC transplantation with treadmill exercise showed additional enhancement of neurogenesis and suppression of apoptosis in the hippocampus. The present study shows that treadmill exercise may aid the therapeutic effect of BMSC transplantation on TBI in rats.

  14. MR spectroscopy-based brain metabolite profiling in propionic acidaemia: metabolic changes in the basal ganglia during acute decompensation and effect of liver transplantation

    Directory of Open Access Journals (Sweden)

    McKiernan Patrick J

    2011-05-01

    replenish a compromised Krebs cycle and that this is a marker of compromised aerobic respiration within brain tissue. Thus there is a need for improved brain protective strategies during acute metabolic decompensations. MRS provides a non-invasive tool for which could be employed to evaluate novel treatments aimed at restoring basal ganglia homeostasis. The results from the liver transplantation sub-group supports the hypothesis that liver transplantation provides systemic metabolic stability by providing a hepatic pool of functional propionyl CoA carboxylase, thus preventing further acute decompensations which are associated with the risk of brain infarction.

  15. Detection of acute renal allograft rejection by analysis of renal tissue proteomics in rat models of renal transplantation

    Directory of Open Access Journals (Sweden)

    Dai Yong

    2008-01-01

    Full Text Available At present, the diagnosis of renal allograft rejection requires a renal biopsy. Clinical management of renal transplant patients would be improved if rapid, noninvasive and reliable biomarkers of rejection were available. This study is designed to determine whether such protein biomarkers can be found in renal-graft tissue proteomic approach. Orthotopic kidney transplantations were performed using Fisher (F344 or Lewis rats as donors and Lewis rats as recipients. Hence, there were two groups of renal transplant models: one is allograft (from F344 to Lewis rats; another is syngrafts (from Lewis to Lewis rats serving as control. Renal tissues were collected 3, 7 and 14 days after transplantation. As many as 18 samples were analyzed by 2-D Electrophoresis and mass spectrometry (MALDI-TOF-TOF-MS. Eleven differentially expressed proteins were identified between groups. In conclusion, proteomic technology can detect renal tissue proteins associated with acute renal allograft rejection. Identification of these proteins as diagnostic markers for rejection in patients′ urine or sera may be useful and non-invasive, and these proteins might serve as novel therapeutic targets that also help to improve the understanding of mechanism of renal rejection.

  16. Brain transplants. A new approach to the therapy of neurodegenerative disease.

    Science.gov (United States)

    Tulipan, N

    1988-05-01

    There is now a wealth of experimental evidence to suggest that transplantation to the brain may ameliorate a variety of neurologic and endocrine disorders. Many unanswered questions remain. Chief among these questions are the duration of any salutary effects and the potential long-term risks to the host CNS. Answers to these questions will only come with carefully controlled long-term clinical studies. Given the high incidence and devastating nature of many of these diseases, such studies will have enormous scientific and social impact. Regardless of the outcome, there is the potential for a greater understanding of the pathologic mechanisms underlying neurodegenerative diseases and, thus, the possibility that definitive therapies will be found as a result.

  17. Safety considerations for transplanting cryopreserved ovarian tissue to restore fertility in female patients who have recovered from Ewing's sarcoma

    DEFF Research Database (Denmark)

    Sørensen, Stine D; Greve, Tine; Wielenga, Vera Timmermans

    2014-01-01

    Ewing's sarcoma (EWS) is a highly malignant cancer in children, adolescents and young adults. The chemotherapy required to treat female EWS patients may cause primary ovarian insufficiency and infertility as a side effect. Cryopreservation of ovarian tissue before the start of chemotherapy can...... potentially preserve fertility. When the patient has been cured and primary ovarian insufficiency has developed, transplantation of frozen/thawed ovarian tissue can restore ovarian function. The tissue is usually collected before chemotherapy is initiated, and malignant cells may contaminate the stored...... of EWS patients and presents a new case of malignant cells in an ovarian biopsy from a girl with EWS....

  18. Safety of Allogeneic Canine Adipose Tissue-Derived Mesenchymal Stem Cell Intraspinal Transplantation in Dogs with Chronic Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Cláudia Cardoso Maciel Escalhão

    2017-01-01

    Full Text Available This is a pilot clinical study primarily designed to assess the feasibility and safety of X-ray-guided percutaneous intraspinal injection of allogeneic canine adipose tissue-derived mesenchymal stem cells in dogs with chronic spinal cord injury. Six dogs with chronic paraplegia (≥six months were intraparenchymally injected with allogeneic cells in the site of lesion. Cells were obtained from subcutaneous adipose tissue of a healthy dog, cultured to passage 3, labeled with 99mTechnetium, and transplanted into the lesion by percutaneous X-ray-guided injection. Digital X-ray efficiently guided cell injection as 99mTechnetium-labeled cells remained in the injection site for at least 24 hours after transplantation. No adverse effects or complications (infection, neuropathic pain, or worsening of neurological function were observed during the 16-week follow-up period after transplantation. Three animals improved locomotion as assessed by the Olby scale. One animal walked without support, but no changes in deep pain perception were observed. We conclude that X-ray-guided percutaneous intraspinal transplantation of allogeneic cells in dogs with chronic spinal cord injury is feasible and safe. The efficacy of the treatment will be assessed in a new study involving a larger number of animals.

  19. Effects of three different types of antifreeze proteins on mouse ovarian tissue cryopreservation and transplantation.

    Directory of Open Access Journals (Sweden)

    Jaewang Lee

    Full Text Available Ovarian tissue (OT cryopreservation is effective in preserving fertility in cancer patients who have concerns about fertility loss due to cancer treatment. However, the damage incurred at different steps during the cryopreservation procedure may cause follicular depletion; hence, preventing chilling injury would help maintain ovarian function.This study was designed to investigate the beneficial effects of different antifreeze proteins (AFPs on mouse ovarian tissue cryopreservation and transplantation.Ovaries were obtained from 5-week-old B6D2F1 mice, and each ovary was cryopreserved using two-step vitrification and four-step warming procedures. In Experiment I, ovaries were randomly allocated into fresh, vitrification control, and nine experimental groups according to the AFP type (FfIBP, LeIBP, type III and concentration (0.1, 1, 10 mg/mL used. After vitrification and warming, 5,790 ovarian follicles were evaluated using histology and TUNEL assays, and immunofluorescence for τH2AX and Rad51 was used to detect DNA double-strand breaks (DSBs and repair (DDR, respectively. In Experiment II, 20 mice were randomly divided into two groups: one where the vitrification and warming media were supplemented with 10 mg/mL LeIBP, and the other where media alone were used (control. Ovaries were then autotransplanted under both kidney capsules 7 days after vitrification together with the addition of 10 mg/mL LeIBP in the vitrification-warming media. After transplantation, the ovarian follicles, the percentage of apoptotic follicles, the extent of the CD31-positive area, and the serum FSH levels of the transplanted groups were compared.In Experiment I, the percentage of total grade 1 follicles was significantly higher in the 10 mg/mL LeIBP group than in the vitrification control, while all AFP-treated groups had significantly improved grade 1 primordial follicle numbers compared with those of the vitrification control. The number of apoptotic (TUNEL

  20. Reconstruction of auto-tissue-engineered lamellar cornea by dynamic culture for transplantation: a rabbit model.

    Science.gov (United States)

    Wu, Zheng; Zhou, Qiang; Duan, Haoyun; Wang, Xiaoran; Xiao, Jianhui; Duan, Hucheng; Li, Naiyang; Li, Chaoyang; Wan, Pengxia; Liu, Ying; Song, Yiyue; Zhou, Chenjing; Huang, Zheqian; Wang, Zhichong

    2014-01-01

    To construct an auto-tissue-engineered lamellar cornea (ATELC) for transplantation, based on acellular porcine corneal stroma and autologous corneal limbal explants, a dynamic culture process, which composed of a submersion culture, a perfusion culture and a dynamic air-liquid interface culture, was performed using appropriate parameters. The results showed that the ATELC-Dynamic possessed histological structure and DNA content that were similar to native lamellar cornea (NLC, p>0.05). Compared to NLC, the protein contents of zonula occludens-1, desmocollin-2 and integrin β4 in ATELC-Dynamic reached 93%, 89% and 73%, respectively. The basal cells of ATELC-Dynamic showed a better differentiation phenotype (K3-, P63+, ABCG2+) compared with that of ATELC in static air-lift culture (ATELC-Static, K3+, P63-, ABCG2-). Accordingly, the cell-cloning efficiency of ATELC-Dynamic (9.72±3.5%) was significantly higher than that of ATELC-Static (2.13±1.46%, p0.05). Rabbit lamellar keratoplasty showed that the barrier function of ATELC-Dynamic was intact, and there were no signs of epithelial shedding or neovascularization. Furthermore, the ATELC-Dynamic group had similar optical properties and wound healing processes compared with the NLC group. Thus, the sequential dynamic culture process that was designed according to corneal physiological characteristics could successfully reconstruct an auto-lamellar cornea with favorable morphological characteristics and satisfactory physiological function.

  1. Bone marrow transplantation modulates tissue macrophage phenotype and enhances cardiac recovery after subsequent acute myocardial infarction.

    Science.gov (United States)

    Protti, Andrea; Mongue-Din, Heloise; Mylonas, Katie J; Sirker, Alexander; Sag, Can Martin; Swim, Megan M; Maier, Lars; Sawyer, Greta; Dong, Xuebin; Botnar, Rene; Salisbury, Jon; Gray, Gillian A; Shah, Ajay M

    2016-01-01

    Bone marrow transplantation (BMT) is commonly used in experimental studies to investigate the contribution of BM-derived circulating cells to different disease processes. During studies investigating the cardiac response to acute myocardial infarction (MI) induced by permanent coronary ligation in mice that had previously undergone BMT, we found that BMT itself affects the remodelling response. Compared to matched naive mice, animals that had previously undergone BMT developed significantly less post-MI adverse remodelling, infarct thinning and contractile dysfunction as assessed by serial magnetic resonance imaging. Cardiac rupture in male mice was prevented. Histological analysis showed that the infarcts of mice that had undergone BMT had a significantly higher number of inflammatory cells, surviving cardiomyocytes and neovessels than control mice, as well as evidence of significant haemosiderin deposition. Flow cytometric and histological analyses demonstrated a higher number of alternatively activated (M2) macrophages in myocardium of the BMT group compared to control animals even before MI, and this increased further in the infarcts of the BMT mice after MI. The process of BMT itself substantially alters tissue macrophage phenotype and the subsequent response to acute MI. An increase in alternatively activated macrophages in this setting appears to enhance cardiac recovery after MI. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Biopsy-diagnosed renal disease in patients after transplantation of other organs and tissues.

    Science.gov (United States)

    Schwarz, A; Haller, H; Schmitt, R; Schiffer, M; Koenecke, C; Strassburg, C; Lehner, F; Gottlieb, J; Bara, C; Becker, J U; Broecker, V

    2010-09-01

    Renal function deteriorates in about half of patients undergoing other transplants. We report the results of 105 renal biopsies from 101 nonrenal transplant recipients (bone marrow 14, liver 41, lung 30, heart 20). Biopsy indications were protracted acute renal failure (9%), creatinine increases (83%), heavy proteinuria (22%), or renal insufficiency before re-transplantation (9%). Histological findings other than nonspecific chronic changes, hypertension-related damage, and signs of chronic CNI toxicity included primary glomerular disease (17%), mostly after liver transplantation (21%) or after bone marrow transplantation (29%), and thrombotic microangiopathy (TMA) namely (10%). TMA had the most serious impact on the clinical course. Besides severe hypertension, one TMA patient died of cerebral hemorrhage, 5 had hemolytic-uremic syndrome, and 6 rapidly developed end-stage renal failure. TMA patients had the shortest kidney survival post-biopsy and, together with patients with acute tubular injury, the shortest kidney and patient survival since transplantation. Nine TMA patients had received CNI, 3 of them concomitantly received an mTOR-inhibitor. CNI toxicity is implicated in most patients with renal failure after transplant of other organs and may play a role in the development of TMA, the most serious complication. However, decreased renal function should not be routinely ascribed to CNI. © 2010 The Authors Journal compilation © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  5. Compliant intracortical implants reduce strains and strain rates in brain tissue in vivo

    Science.gov (United States)

    Sridharan, Arati; Nguyen, Jessica K.; Capadona, Jeffrey R.; Muthuswamy, Jit

    2015-06-01

    Objective. The objective of this research is to characterize the mechanical interactions of (1) soft, compliant and (2) non-compliant implants with the surrounding brain tissue in a rodent brain. Understanding such interactions will enable the engineering of novel materials that will improve stability and reliability of brain implants. Approach. Acute force measurements were made using a load cell in n = 3 live rats, each with 4 craniotomies. Using an indentation method, brain tissue was tested for changes in force using established protocols. A total of 4 non-compliant, bare silicon microshanks, 3 non-compliant polyvinyl acetate (PVAc)-coated silicon microshanks, and 6 compliant, nanocomposite microshanks were tested. Stress values were calculated by dividing the force by surface area and strain was estimated using a linear stress-strain relationship. Micromotion effects from breathing and vascular pulsatility on tissue stress were estimated from a 5 s interval of steady-state measurements. Viscoelastic properties were estimated using a second-order Prony series expansion of stress-displacement curves for each shank. Main results. The distribution of strain values imposed on brain tissue for both compliant nanocomposite microshanks and PVAc-coated, non-compliant silicon microshanks were significantly lower compared to non-compliant bare silicon shanks. Interestingly, step-indentation experiments also showed that compliant, nanocomposite materials significantly decreased stress relaxation rates in the brain tissue at the interface (p brain tissue. Understanding the material behavior at the site of tissue contact will help to improve neural implant design.

  6. Split cornea transplantation for 2 recipients: a new strategy to reduce corneal tissue cost and shortage.

    Science.gov (United States)

    Heindl, Ludwig M; Riss, Stephan; Bachmann, Bjoern O; Laaser, Kathrin; Kruse, Friedrich E; Cursiefen, Claus

    2011-02-01

    remained clear up to 6 months after surgery. Split use of donor corneal tissue for combined DALK and DMEK procedures in 2 recipients on the same surgery day is a promising strategy to reduce donor shortage and cost in corneal transplantation surgery in the future. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  7. Results from a horizon scan on risks associated with transplantation of human organs, tissues and cells: from donor to patient.

    Science.gov (United States)

    Herberts, C A; Park, M V D Z; Pot, J W G A; de Vries, C G J C A

    2015-03-01

    The successful transplantation of human materials such as organs, tissues and cells into patients does not only depend on the benefits, but also on the mitigation of risks. To gain insight into recent publications on risks associated with the process of transferring human materials from donor to recipient we performed a horizon scan by reviewing scientific literature and news websites of 2011 on this subject. We found there is ample information on how extended donor criteria, such as donor age, affect the survival rates of organs or patients. Interestingly, gender mismatch does not appear to be a major risk factor in organ rejection. Data on risks of donor tumor transmission was very scarce; however, risk categories for various tumor types have been suggested. In order to avoid rejection, a lot of research is directed towards engineering tissues from a patient's own tissues and cells. Some but not all of these developments have reached the clinic. Developments in the field of stem cell therapy are rapid. However, many hurdles are yet to be overcome before these cells can be applied on a large scale in the clinic. The processes leading to genetic abnormalities in cells differentiated from stem cells need to be identified in order to avoid transplantation of aberrant cells. New insights have been obtained on storage and preservation of human materials, a critical step for success of their clinical use. Likewise, quality management systems have been shown to improve the quality and safety of human materials used for transplantation.

  8. The effects of grafted mesenchymal stem cells labeled with iron oxide or cobalt-zinc-iron nanoparticles on the biological macromolecules of rat brain tissue extracts.

    Science.gov (United States)

    Novotna, Bozena; Herynek, Vit; Rossner, Pavel; Turnovcova, Karolina; Jendelova, Pavla

    2017-01-01

    Rat mesenchymal stem cells (rMSCs) labeled with 1) poly-l-lysine-coated superparamagnetic iron oxide nanoparticles or 2) silica-coated cobalt-zinc-iron nanoparticles were implanted into the left brain hemisphere of rats, to assess their effects on the levels of oxidative damage to biological macromolecules in brain tissue. Controls were implanted with unlabeled rMSCs. Animals were sacrificed 24 hours or 4 weeks after the treatment, and the implantation site along with the surrounding tissue was isolated from the brain. At the same intervals, parallel groups of animals were scanned in vivo by magnetic resonance imaging (MRI). The comet assay with enzymes of excision DNA repair (endonuclease III and formamidopyrimidine-DNA glycosylase) was used to analyze breaks and oxidative damage to DNA in the brain tissue. Oxidative damage to proteins and lipids was determined by measuring the levels of carbonyl groups and 15-F2t-isoprostane (enzyme-linked immunosorbent assay). MRI displayed implants of labeled cells as extensive hypointense areas in the brain tissue. In histological sections, the expression of glial fibrillary acidic protein and CD68 was analyzed to detect astrogliosis and inflammatory response. Both contrast labels caused a similar response in the T2-weighted magnetic resonance (MR) image and the signal was clearly visible within 4 weeks after implantation of rMSCs. No increase of oxidative damage to DNA, lipids, or proteins over the control values was detected in any sample of brain tissue from the treated animals. Also, immunohistochemistry did not indicate any serious tissue impairment around the graft. Both tested types of nanoparticles appear to be prospective and safe labels for tracking the transplanted cells by MR.

  9. Docosahexaenoic acid (DHA) enhances the therapeutic potential of neonatal neural stem cell transplantation post-Traumatic brain injury.

    Science.gov (United States)

    Ghazale, Hussein; Ramadan, Naify; Mantash, Sara; Zibara, Kazem; El-Sitt, Sally; Darwish, Hala; Chamaa, Farah; Boustany, Rose Mary; Mondello, Stefania; Abou-Kheir, Wassim; Soueid, Jihane; Kobeissy, Firas

    2018-03-15

    Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide with 1.5 million people inflicted yearly. Several neurotherapeutic interventions have been proposed including drug administration as well as cellular therapy involving neural stem cells (NSCs). Among the proposed drugs is docosahexaenoic acid (DHA), a polyunsaturated fatty acid, exhibiting neuroprotective properties. In this study, we utilized an innovative intervention of neonatal NSCs transplantation in combination with DHA injections in order to ameliorate brain damage and promote functional recovery in an experimental model of TBI. Thus, NSCs derived from the subventricular zone of neonatal pups were cultured into neurospheres and transplanted in the cortex of an experimentally controlled cortical impact mouse model of TBI. The effect of NSC transplantation was assessed alone and/or in combination with DHA administration. Motor deficits were evaluated using pole climbing and rotarod tests. Using immunohistochemistry, the effect of transplanted NSCs and DHA treatment was used to assess astrocytic (Glial fibrillary acidic protein, GFAP) and microglial (ionized calcium binding adaptor molecule-1, IBA-1) activity. In addition, we quantified neuroblasts (doublecortin; DCX) and dopaminergic neurons (tyrosine hydroxylase; TH) expression levels. Combined NSC transplantation and DHA injections significantly attenuated TBI-induced motor function deficits (pole climbing test), promoted neurogenesis, coupled with an increase in glial reactivity at the cortical site of injury. In addition, the number of tyrosine hydroxylase positive neurons was found to increase markedly in the ventral tegmental area and substantia nigra in the combination therapy group. Immunoblotting analysis indicated that DHA+NSCs treated animals showed decreased levels of 38kDa GFAP-BDP (breakdown product) and 145kDa αII-spectrin SBDP indicative of attenuated calpain/caspase activation. These data demonstrate that prior

  10. The Conductivity of Brain Tissues: Comparison of Results in Vivo and In Vitro Measurements

    Science.gov (United States)

    2001-10-25

    situation in the living piglet . In [7] the estimated resistivity ratio of skull and brain is 14:1. The same ratio calculated from the results of in vivo...brain. Presumably measured from tissue samples at 390C. [19] Foster et al. 1979 2,67 (10 MHz) 3,33 (10 MHz) Tissue samples from dog’s brain at 370C. [22...Biol., vol. 41, pp. 2251-2269, 1996. [13] K. R. Foster , “Dielectric properties of tissues,” In: Bronzino J. D. (ed.). The

  11. Ionic charge transport between blockages: Sodium cation conduction in freshly excised bulk brain tissue

    Directory of Open Access Journals (Sweden)

    David Emin

    2015-08-01

    Full Text Available 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.

  12. Ionic charge transport between blockages: Sodium cation conduction in freshly excised bulk brain tissue

    Energy Technology Data Exchange (ETDEWEB)

    Emin, David, E-mail: emin@unm.edu [Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM 87131 (United States); Akhtari, Massoud [Semple Institutes for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095 (United States); Ellingson, B. M. [Department of Radiology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095 (United States); Mathern, G. W. [Department of Neurosurgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095 (United States)

    2015-08-15

    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.

  13. Tissue Engineering to Improve Immature Testicular Tissue and Cell Transplantation Outcomes: One Step Closer to Fertility Restoration for Prepubertal Boys Exposed to Gonadotoxic Treatments.

    Science.gov (United States)

    Del Vento, Federico; Vermeulen, Maxime; de Michele, Francesca; Giudice, Maria Grazia; Poels, Jonathan; des Rieux, Anne; Wyns, Christine

    2018-01-18

    Despite their important contribution to the cure of both oncological and benign diseases, gonadotoxic therapies present the risk of a severe impairment of fertility. Sperm cryopreservation is not an option to preserve prepubertal boys' reproductive potential, as their seminiferous tubules only contain spermatogonial stem cells (as diploid precursors of spermatozoa). Cryobanking of human immature testicular tissue (ITT) prior to gonadotoxic therapies is an accepted practice. Evaluation of cryopreserved ITT using xenotransplantation in nude mice showed the survival of a limited proportion of spermatogonia and their ability to proliferate and initiate differentiation. However, complete spermatogenesis could not be achieved in the mouse model. Loss of germ cells after ITT grafting points to the need to optimize the transplantation technique. Tissue engineering, a new branch of science that aims at improving cellular environment using scaffolds and molecules administration, might be an approach for further progress. In this review, after summarizing the lessons learned from human prepubertal testicular germ cells or tissue xenotransplantation experiments, we will focus on the benefits that might be gathered using bioengineering techniques to enhance transplantation outcomes by optimizing early tissue graft revascularization, protecting cells from toxic insults linked to ischemic injury and exploring strategies to promote cellular differentiation.

  14. Motor-Evoked Potential Confirmation of Functional Improvement by Transplanted Bone Marrow Mesenchymal Stem Cell in the Ischemic Rat Brain

    Directory of Open Access Journals (Sweden)

    Dong-Kyu Jang

    2011-01-01

    Full Text Available This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (<.05. MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway.

  15. Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery

    NARCIS (Netherlands)

    Blumcke, Ingmar; Spreafico, Roberto; Haaker, Gerrit; Coras, Roland; Kobow, Katja; Bien, Christian G.; Pfäfflin, Margarete; Elger, Christian; Widman, Guido; Schramm, Johannes; Becker, Albert; Braun, Kees P.; Leijten, Frans; Baayen, Johannes C.; Aronica, Eleonora; Chassoux, Francine; Hamer, Hajo; Stefan, Hermann; Rössler, Karl; Thom, Maria; Walker, Matthew C.; Sisodiya, Sanjay M.; Duncan, John S.; McEvoy, Andrew W.; Pieper, Tom; Holthausen, Hans; Kudernatsch, Manfred; Meencke, H. Joachim; Kahane, Philippe; Schulze-Bonhage, Andreas; Zentner, Josef; Heiland, Dieter H.; Urbach, Horst; Steinhoff, Bernhard J.; Bast, Thomas; Tassi, Laura; Lo Russo, Giorgio; Özkara, Cigdem; Oz, Buge; Krsek, Pavel; Vogelgesang, Silke; Runge, Uwe; Lerche, Holger; Weber, Yvonne; Honavar, Mrinalini; Pimentel, José; Arzimanoglou, Alexis; Ulate-Campos, Adriana; Noachtar, Soheyl; Hartl, Elisabeth; Schijns, Olaf; Guerrini, Renzo; Barba, Carmen; Jacques, Thomas S.; Cross, J. Helen; Feucht, Martha; Mühlebner, Angelika; Grunwald, Thomas; Trinka, Eugen; Winkler, Peter A.; Gil-Nagel, Antonio; Toledano Delgado, Rafael; Mayer, Thomas; Lutz, Martin; Zountsas, Basilios; Garganis, Kyriakos; Rosenow, Felix; Hermsen, Anke; von Oertzen, Tim J.; Diepgen, Thomas L.; Avanzini, Giuliano; Aparicio, Javier; Bento, Conceição; Beckervordersandforth, Jan; Buccoliero, Annamaria; Cabral, Pedro; Chamadoira, Clara; Colon, Albert; Chabardès, Stéphan; Carpenter, Stirling; Czech, Thomas; Dressler, Anastasia; Deleo, Francesco; Dílio, Alves; Dings, Jim; Devaux, Bertrand; de Tisi, Jane; de Bellescize, Julitta; Ebner, Alois; Franke, Kerstin; Groeppel, Gudrun; Giordano, Flavio; Gozzo, Francesca; Garbelli, Rita; Guenot, Marc; García‐Morales, Irene; Gómez‐Angulo, Juan Carlos; Garcia, Gemma; Hainfellner, Johannes A.; Höfler, Julia; Hoogland, Govert; Hendriks, Marc; Hofman, Paul; Harding, Brian; Huppertz, Hans‐Jürgen; Herms, Jochen; Hilkman, Danny M. W.; Hamelin, Sophie; Idema, Sander; Jansen, Floor E.; Jahodova, Alena; Keeley, Angus; Kalss, Gudrun; Kudr, Martin; Kroell, Judith; Kokkinos, Vasileios; Keo Kosal, Pascale; Kalbhenn, Thilo; Leitinger, Markus; Landré, Elisabeth; Melo Pires, Manuel; Matas, Andreia; Mann, Michael W.; Ostrowsky‐Coste, Karine; Prinz, Marco; Puttinger, Gertraud; Peraud, Aurelia; Rangel Pinho, Rui; Romero, Clara; Rego, Ricardo; Rouhl, Rob; Ryvlin, Philippe; Rumia, Jordi; Rampp, Stefan; Scholl, Theresa; Schulz, Reinhard; Stone, Thomas J.; Streichenberger, Nathalie; Tisdall, Martin; Turak, Baris; Taipa, Ricardo; Uzan, Mustafa; van Kranen‐Mastenbroek, Vivianne; Varlet, Pascale; Vlooswijk, Marielle; Wagner, Louis; Weis, Serge

    2017-01-01

    Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy. We report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures

  16. Blood BDNF concentrations reflect brain-tissue BDNF levels across species

    DEFF Research Database (Denmark)

    Klein, Anders B; Williamson, Rebecca; Santini, Martin A

    2011-01-01

    Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been...... no studies directly comparing blood BDNF levels to brain BDNF levels in different species. We examined blood, serum, plasma and brain-tissue BDNF levels in three different mammalian species: rat, pig, and mouse, using an ELISA method. As a control, we included an analysis of blood and brain tissue from...... conditional BDNF knockout mice and their wild-type littermates. Whereas BDNF could readily be measured in rat blood, plasma and brain tissue, it was undetectable in mouse blood. In pigs, whole-blood levels of BDNF could not be measured with a commercially available ELISA kit, but pig plasma BDNF levels (mean...

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

    Science.gov (United States)

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

    2016-10-18

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

  18. Influence of liver pathology on markers of postmortem brain tissue quality.

    Science.gov (United States)

    Sheedy, Donna; Say, Meichien; Stevens, Julia; Harper, Clive G; Kril, Jillian J

    2012-01-01

    Postmortem brain tissue provides an important resource to investigate various brain disorders, including those resulting from the effects of alcohol abuse. Unlike the traditionally recognized confounders to tissue quality (e.g., coma, hypoxia), our understanding of the effects of liver disease is incomplete. The aim of this study was to determine the effects of liver pathology, and in particular cirrhosis resulting in hepatic encephalopathy (HE), on 2 postmortem brain tissue quality markers, brain pH and RNA integrity. We measured tissue quality markers in a cohort of alcohol abuse and control cases collected by the NSW Tissue Resource Centre. Cerebellar tissue was used to evaluate both brain pH and RNA quality (as indicated by the RNA integrity number: RIN). A histological assessment was performed on each case to exclude coexisting pathologies (e.g., cerebrovascular disease, hypoxic encephalopathy, neurodegenerative disease) and to assess the presence or absence of HE. Autopsy reports were reviewed for liver pathology and toxicology. Analysis revealed that cases of alcohol abuse had a lower mean (±SD) brain pH, 6.46 (±0.3) as compared with the control mean 6.64 (±0.2). The mean RIN for the alcohol abuse group was 6.97 (±1.3) and controls 7.66 (±0.5). The severity of liver pathology affected both brain pH (p brain pH (p = 0.0019). The results show that the presence of cirrhosis and, more so, HE reduces the pH and RIN of postmortem brain tissue. Copyright © 2011 by the Research Society on Alcoholism.

  19. Effect of Cerebrospinal Fluid Drainage on Brain Tissue Oxygenation in Traumatic Brain Injury.

    Science.gov (United States)

    Akbik, Omar S; Krasberg, Mark; Nemoto, Edwin M; Yonas, Howard

    2017-11-15

    The effectiveness of cerebrospinal fluid (CSF) drainage in lowering high intracranial pressure (ICP) is well established in severe traumatic brain injury (TBI). Recently, however, the use of external ventricular drains (EVDs) and ICP monitors in TBI has come under question. The aim of this retrospective study was to investigate the effect of CSF drainage on brain tissue oxygenation (PbtO2). Using a multi-modality monitoring system, we continuously monitored PbtO2 and parenchymal ICP during CSF drainage events via a ventriculostomy in 40 patients with severe TBI. Measurements were time-locked continuous recordings on a Component Neuromonitoring System in a neuroscience intensive care unit. We further selected for therapeutic CSF drainage events initiated at ICP values above 25 mm Hg and analyzed the 4-min periods before and after drainage for the physiologic variables ICP, cerebral perfusion pressure (CPP), and PbtO2. We retrospectively identified 204 CSF drainage events for ICP EVD-opening values greater than 25 mm Hg in 23 patients. During the 4 min of opened EVD, ICP decreased by 5.7 ± 0.6 mm Hg, CPP increased by 4.1 ± 1.2 mm Hg, and PbtO2 increased by 1.15 ± 0.26 mm Hg. ICP, CPP, and PbtO2 all improved with CSF drainage at ICP EVD-opening values above 25 mm Hg. Although the average PbtO2 changes were small, a clinically significant change in PbtO2 of 5 mm Hg or greater occurred in 12% of CSF drainage events, which was correlated with larger decreases in ICP, displaying a complex relationship between ICP and PbtO2 that warrants further studies.

  20. Evaluation of tissue-equivalent materials to be used as human brain tissue substitute in dosimetry for diagnostic radiology

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, C.C., E-mail: cassio.c.ferreira@gmail.co [Departamento de Fisica, Universidade Federal de Sergipe, Postal Code 353, Sergipe-SE 49100-000 (Brazil); Ximenes Filho, R.E.M., E-mail: raimundoximenes@hotmail.co [Departamento de Fisica, Universidade Federal de Sergipe, Postal Code 353, Sergipe-SE 49100-000 (Brazil); Vieira, J.W., E-mail: jwvieira@br.inter.ne [Centro Federal de Educacao Tecnologica de Pernambuco (CEFET-PE), Av. Professor Luiz Freire, 500 Curado, CEP 50740-540, Recife (Brazil); Escola Politecnica de Pernambuco, Universidade de Pernambuco (EPP/UPE), Rua Benfica, 455, Madalena, CEP 50720-001, Recife (Brazil); Tomal, A., E-mail: alessandratomal@pg.ffclrp.usp.b [Departamento de Fisica e Matematica, FFCLRP, Universidade de Sao Paulo, Ribeirao Preto-SP 14040-90 (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.b [Departamento de Fisica e Matematica, FFCLRP, Universidade de Sao Paulo, Ribeirao Preto-SP 14040-90 (Brazil); Garcia, C.A.B., E-mail: cgarcia@ufs.b [Departamento de Quimica, Universidade Federal de Sergipe, Postal Code 353, Sergipe-SE 49100-000 (Brazil); Maia, A.F., E-mail: afmaia@ufs.b [Departamento de Fisica, Universidade Federal de Sergipe, Postal Code 353, Sergipe-SE 49100-000 (Brazil)

    2010-08-15

    Tissue-equivalent materials to be used as substitutes for human brain tissue in dosimetry for diagnostic radiology have been investigated in terms of calculated total mass attenuation coefficient ({mu}/{rho}), calculated mass energy-absorption coefficient ({mu}{sub en}/{rho}) and absorbed dose. Measured linear attenuation coefficients ({mu}) have been used for benchmarking the calculated total mass attenuation coefficient ({mu}/{rho}). The materials examined were bolus, nylon (registered) , orange articulation wax, red articulation wax, PMMA (polymethylmethacrylate), bees wax, paraffin I, paraffin II, pitch and water. The results show that water is the best substitute for brain among the materials investigated. The average percentage differences between the calculated {mu}/{rho} and {mu}{sub en}/{rho} coefficients for water and those for brain were 1.0% and 2.5%, respectively. Absorbed doses determined by Monte Carlo methods confirm water as being the best brain substitute to be used in dosimetry for diagnostic radiology, showing maximum difference of 0.01%. Additionally this study showed that PMMA, a material often used for the manufacturing of head phantoms for computed tomography, cannot be considered to be a suitable substitute for human brain tissue in dosimetry.

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

    Science.gov (United States)

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

    2016-03-01

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

  2. Medawar's legacy to cellular immunology and clinical transplantation: a commentary on Billingham, Brent and Medawar (1956) ‘Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance’

    Science.gov (United States)

    Simpson, Elizabeth

    2015-01-01

    ‘Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance’, published in Philosophical Transactions B in 1956 by Peter Medawar and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert Billingham, is a full description of the concept of acquired transplantation tolerance. Their 1953 Nature paper (Billingham RE et al. 1953 Nature 172, 603–606. (doi:10.1038/172603a0)) had provided initial evidence with experimental results from a small number of neonatal mice, with mention of similar findings in chicks. The Philosophical Transactions B 1956 paper is clothed with an astonishing amount of further experimental detail. It is written in Peter Medawar's landmark style: witty, perceptive and full of images that can be recalled even when details of the supporting information have faded. Those images are provided not just by a series of 20 colour plates showing skin graft recipient mice, rats, rabbits, chickens and duck, bearing fur or plumage of donor origin, but by his choice of metaphor, simile and analogy to express the questions being addressed and the interpretation of their results, along with those of relevant published data and his prescient ideas of what the results might portend. This work influenced both immunology researchers and clinicians and helped to lay the foundations for successful transplantation programmes. It led to the award of a Nobel prize in 1960 to Medawar, and subsequently to several scientists who advanced these areas. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society. PMID:25750245

  3. Medawar's legacy to cellular immunology and clinical transplantation: a commentary on Billingham, Brent and Medawar (1956) 'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance'.

    Science.gov (United States)

    Simpson, Elizabeth

    2015-04-19

    'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance', published in Philosophical Transactions B in 1956 by Peter Medawar and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert Billingham, is a full description of the concept of acquired transplantation tolerance. Their 1953 Nature paper (Billingham RE et al. 1953 Nature 172, 603-606. (doi:10.1038/172603a0)) had provided initial evidence with experimental results from a small number of neonatal mice, with mention of similar findings in chicks. The Philosophical Transactions B 1956 paper is clothed with an astonishing amount of further experimental detail. It is written in Peter Medawar's landmark style: witty, perceptive and full of images that can be recalled even when details of the supporting information have faded. Those images are provided not just by a series of 20 colour plates showing skin graft recipient mice, rats, rabbits, chickens and duck, bearing fur or plumage of donor origin, but by his choice of metaphor, simile and analogy to express the questions being addressed and the interpretation of their results, along with those of relevant published data and his prescient ideas of what the results might portend. This work influenced both immunology researchers and clinicians and helped to lay the foundations for successful transplantation programmes. It led to the award of a Nobel prize in 1960 to Medawar, and subsequently to several scientists who advanced these areas. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.

  4. Pancreas transplant

    Science.gov (United States)

    ... A pancreas transplant is surgery to implant a healthy pancreas from a donor into a person with diabetes. Pancreas transplants give ... chance to stop taking insulin injections. Description The healthy pancreas is taken from a donor who is brain dead, but is still on ...

  5. GLOBAL CONSULTATION ON ESTABLISHMENT A UNIFIED SURVEILLANCE SYSTEM FOR DONATION AND TRANSPLANTATION OF ORGANS, TISSUES AND CELLS OF HUMAN ORIGIN

    Directory of Open Access Journals (Sweden)

    O. V. Orlova

    2011-01-01

    Full Text Available From from February 7th to 9th 2011, the World Health Organization (WHO, the Italian National Transplant Cen- tre and the EU-funded Project «Vigilance and Surveillance of Substances of Human Origin» joined forces to organise a major global consultation that took place in Bologna, Italy. The scope of the project included organs, tissues and cells for transplantation and for assisted reproduction. The participants represented regulatory and non-regulatory government agencies, professional societies and scientific and clinical specialities from all WHO regions. The meeting explored the work already carried out on-line and agreed on priorities for the future deve- lopment of the Project «Vigilance and Surveillance of Substances of Human Origin». 

  6. Periimplant changes in different transplanted soft tissues around loaded endosseous implants in patients after oral tumor surgery.

    Science.gov (United States)

    Kovács, Adorján F; Wallowy, Phillip; Stefenelli, Ulrich; Landau, Stephan

    2013-12-01

    To examine periimplant reaction of transplanted soft tissues foreign to oral cavity when compared with local gingiva. In 58 oral cancer patients, 210 dental implants were inserted mainly in the mandible after radical surgery and reconstruction. Ninety-six implants penetrated transplants (split skin, mucosal, platysma, pectoralis major, and intestinal) and were compared with 114 implants penetrating local gingiva. Prosthetic treatment consisted of telescopic or bar-retained overdentures or (in case of intestinal grafts) implant-supported fixed prostheses. Follow-up lasted between 30 and 60 months. Plaque index, sulcus bleeding index, pocket probing depth, and width of vestibular-/oral attached mucosa were measured. Plaque index (before second year; P oral cancer patients. Split skin and mucosal grafts had worst performance.

  7. Multimodal optical imaging database from tumour brain human tissue: endogenous fluorescence from glioma, metastasis and control tissues

    Science.gov (United States)

    Poulon, Fanny; Ibrahim, Ali; Zanello, Marc; Pallud, Johan; Varlet, Pascale; Malouki, Fatima; Abi Lahoud, Georges; Devaux, Bertrand; Abi Haidar, Darine

    2017-02-01

    Eliminating time-consuming process of conventional biopsy is a practical improvement, as well as increasing the accuracy of tissue diagnoses and patient comfort. We addressed these needs by developing a multimodal nonlinear endomicroscope that allows real-time optical biopsies during surgical procedure. It will provide immediate information for diagnostic use without removal of tissue and will assist the choice of the optimal surgical strategy. This instrument will combine several means of contrast: non-linear fluorescence, second harmonic generation signal, reflectance, fluorescence lifetime and spectral analysis. Multimodality is crucial for reliable and comprehensive analysis of tissue. Parallel to the instrumental development, we currently improve our understanding of the endogeneous fluorescence signal with the different modalities that will be implemented in the stated. This endeavor will allow to create a database on the optical signature of the diseased and control brain tissues. This proceeding will present the preliminary results of this database on three types of tissues: cortex, metastasis and glioblastoma.

  8. 86 successful births and 9 ongoing pregnancie s worldwide in women transplanted with frozen-thawed ovarian tissue

    DEFF Research Database (Denmark)

    Jensen, Annette Klüver; Macklon, Kirsten Tryde; Fedder, Jens

    2017-01-01

    : PubMed was searched for papers of deliveries resulting from ovarian tissue cryopreservation (OTC). Seven women underwent OTC prior to chemotherapy. Four of these women still had low ovarian function and had tried to conceive. They therefore had tissue autotransplanted to augment their fertility....... The other three women had developed premature ovarian insufficiency (POI) after the end of treatment. RESULTS: Worldwide, approximately 95 children have been born or will be born in the near future from OTC, including these 9 new children. Information on the perinatal outcome was found on 40 children...... Danish women became pregnant within 1-3 years after transplantation. They gave birth to nine healthy children. CONCLUSION: The data is reassuring and further suggests that cryopreservation of ovarian tissue is becoming an established fertility preservation method. The seven Danish women reported...

  9. FAMILY CONSENT FOR ORGAN OR TISSUE REMOVAL FROM A DECEASED PERSON FOR TRANSPLANTATION PURPOSES IN THE REPUBLIC OF CROATIA

    Directory of Open Access Journals (Sweden)

    Tomislav Nedić

    2017-04-01

    Full Text Available The Republic of Croatia is a country with the system of presumed consent donation of organs and tissues after death, where the consent of the family, according to law, is not one of the conditions for organ or tissue removal for transplantation purposes. However, the consent is a condition required by the Codex of Medical Ethics and Deontology. The author primary proposes harmonization of the Codex with current legislation. Accordingly, this paper primarily analyses the typology of the Codex, ethical issues and ethical and positivist reasons to harmonize the Codex with current legislation. Furthermore, although the author in the first place considers that the Codex should be in line with legislation, he also considers the provision of family consent for organ and tissue removal itself flawed and poorly developed. In this regard, the author considers the comparative legislation and judgments of the European Court of Human Rights, analyses current provisions of the Codex in the part of the removal and transplantation of organs and tissues from deceased persons, states the facts that the Codex should contain so as to make the mechanism of family consent for organ and tissue removal and donation after death more effective. In fact, if the author’s original proposal for harmonization of the Codex with the current legislation is not accepted, a more detailed and precise elaboration of the mentioned current provisions of the Codex will be suggested. This will include exact definition of the family and relatives, exact deadlines and ways of informing the family, but also refining the concept of “ethical“ according to the Codex in part of the organ and tissue donation and removal from the deceased person.

  10. Neuroprotective and behavioral efficacy of nerve growth factor-transfected hippocampal progenitor cell transplants after experimental traumatic brain injury.

    Science.gov (United States)

    Philips, M F; Mattiasson, G; Wieloch, T; Björklund, A; Johansson, B B; Tomasevic, G; Martínez-Serrano, A; Lenzlinger, P M; Sinson, G; Grady, M S; McIntosh, T K

    2001-05-01

    Immortalized neural progenitor cells derived from embryonic rat hippocampus (HiB5), were transduced ex vivo with the gene for mouse nerve growth factor (NGF) to secrete NGF (NGF-HiB5) at 2 ng/hr/10(5) cells in culture. Fifty-nine male Wistar rats weighing 300 to 370 g each were anesthetized with 60 mg/kg sodium pentobarbital and subjected to lateral fluid-percussion brain injury of moderate severity (2.3-2.4 atm, 34 rats) or sham injury (25 rats). At 24 hours postinjury, 2 microl (150,000 cells/microl) of [3H]thymidine-labeled NGF-HiB5 cells were transplanted stereotactically into three individual sites in the cerebral cortex adjacent to the injury site (14 rats). Separate groups of brain-injured rats received nontransfected (naive [n])-HiB5 cells (12 animals) or cell suspension vehicle (eight animals). One week postinjury, animals underwent neurological evaluation for motor function and cognition (Morris water maze) and were killed for histological, autoradiographic, and immunocytochemical analysis. Viable HiB5 cell grafts were identified in all animals, together with reactive microglia and macrophages located throughout the periinjured parenchyma and grafts (OX-42 immunohistochemistry). Brain-injured animals transplanted with either NGF-HiB5 or n-HiB5 cells displayed significantly improved neuromotor function (p < 0.05) and spatial learning behavior (p < 0.005) compared with brain-injured animals receiving microinjections of vehicle alone. A significant reduction in hippocampal CA3 cell death was observed in brain-injured animals receiving transplants of NGF-HiB5 cells compared with those receiving n-HiB5 cells or vehicle (p < 0.025). This study demonstrates that immortalized neural stem cells that have been retrovirally transduced to produce NGF can markedly improve cognitive and neuromotor function and rescue hippocampal CA3 neurons when transplanted into the injured brain during the acute posttraumatic period.

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

    Science.gov (United States)

    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

  12. Sequential therapy of vacuum sealing drainage and free-flap transplantation for children with extensive soft-tissue defects below the knee in the extremities.

    Science.gov (United States)

    Li, Run-Guang; Yu, Bin; Wang, Gang; Chen, Bin; Qin, Cheng-He; Guo, Gang; Jin, Dan; Ren, Gao-Hong

    2012-06-01

    The aim of the study is to evaluate the surgical technique and clinical significance of the sequential therapy of vacuum sealing drainage (VSD) and free-flap transplantation for children with extensive soft-tissue defects below the knee in the extremities. Twenty-two children (aged from 3 to 10 years) received sequential therapy of VSD and free-flap transplantation. All cases suffered from extensive area soft-tissue defects and exposure or partial defects of bones, tendons and other deep tissues. The wound sizes varied from 10 cm × 6 cm to 30 cm × 22 cm. Amongst 22 cases, 12 cases had fresh wounds and the remaining 10 children had necrotising infection. After complete debridement, the wounds were covered by VSD. External fixation or Kirschner-wire fixation should be performed for the cases complicated by unsteady fractures. After the removal of negative pressure VSD devices, free-flap transplantations were performed in 8 cases after debridement, and 14 cases received combined therapy of free-flap transplantation and skin grafting depending upon the severity of soft-tissue and deep-tissue defects. The flap survival and wound healing were followed up postoperatively. After VSD treatment, the infection of deep-tissue exposure was effectively prevented, and granulation tissues surrounding the exposed areas of tendons and bones grew well. All patients who received free-flap transplantation at the second stage survived without the occurrence of vascular crisis, infection or sinus formation. During follow-up ranging from 6 to 24 months, all the patients were satisfied with the morphological appearance and functional recovery of the affected limbs. Sequential therapy of VSD and free-flap transplantation can serve as a reliable option for children with extensive soft-tissue defects below the knee in the extremities and exposed deep tissues, after complete debridement, which significantly shortens remedy period, enhances success rate for surgery and achieves maximal

  13. Engraftment potential of adipose tissue-derived human mesenchymal stem cells after transplantation in the fetal rabbit.

    Science.gov (United States)

    Martínez-González, Itziar; Moreno, Rafael; Petriz, Jordi; Gratacós, Eduard; Aran, Josep M

    2012-12-10

    Due to their favorable intrinsic features, including engraftment, differentiation, and immunomodulatory potential, adult mesenchymal stem cells (MSCs) have been proposed for therapeutic in utero intervention. Further improvement of such attributes for particular diseases might merely be achieved by ex vivo MSC genetic engineering previous to transplantation. Here, we evaluated for the first time the feasibility, biodistribution, long-term engraftment, and transgenic enhanced green fluorescent protein (EGFP) expression of genetically engineered human adipose tissue-derived MSCs (EGFP(+)-ASCs) after intra-amniotic xenotransplantation at E17 of gestation into our validated pregnant rabbit model. Overall, the procedure was safe (86.4% survival rate; absence of anatomical defects). Stable, low-level engraftment of EGFP(+)-ASCs was confirmed by assessing the presence of the pWT-EGFP lentiviral provirus in the young transplanted rabbit tissues. Accordingly, similar frequencies of provirus-positive animals were found at both 8 weeks (60%) and 16 weeks (66.7%) after in utero intervention. The presence of EGFP(+)-ASCs was more frequent in respiratory epithelia (lung and trachea), according to the route of administration. However, we were unable to detect EGFP expression, neither by real-time polymerase chain reaction nor by immunohistochemistry, in the provirus-positive tissues, suggesting EGFP transgene silencing mediated by epigenetic events. Moreover, we noticed lack of both host cellular immune responses against xenogeneic ASCs and humoral immune responses against transgenic EGFP. Therefore, the fetal microchimerism achieved by the EGFP(+)-ASCs in the young rabbit hosts indicates induction of donor-specific tolerance after fetal rabbit xenotransplantation, which should boost postnatal transplantation for the early treatment/prevention of many devastating congenital disorders.

  14. Quantifying brain tissue volume in multiple sclerosis with automated lesion segmentation and filling

    OpenAIRE

    Valverde, Sergi; Oliver, Arnau; Roura, Eloy; Pareto, Deborah; Vilanova, Joan C.; Ramió-Torrentà, LLuís; Sastre-Garriga, Jaume; Montalban, Xavier; Rovira, Àlex; Lladó, Xavier

    2015-01-01

    Lesion filling has been successfully applied to reduce the effect of hypo-intense T1-w Multiple Sclerosis (MS) lesions on automatic brain tissue segmentation. However, a study of fully automated pipelines incorporating lesion segmentation and lesion filling on tissue volume analysis has not yet been performed. Here, we analyzed the % of error introduced by automating the lesion segmentation and filling processes in the tissue segmentation of 70 clinically isolated syndrome patient images. Fir...

  15. Prostacyclin infusion may prevent secondary damage in pericontusional brain tissue

    DEFF Research Database (Denmark)

    Reinstrup, Peter; Nordström, Carl-Henrik

    2011-01-01

    Prostacyclin is a potent vasodilator, inhibitor of leukocyte adhesion, and platelet aggregation, and has been suggested as therapy for cerebral ischemia. A case of focal traumatic brain lesion that was monitored using intracerebral microdialysis, and bedside analysis and display is reported here........ When biochemical signs of cerebral ischemia progressed, i.v. infusion of prostacyclin was started....

  16. Probabilistic brain tissue segmentation in neonatal magnetic resonance imaging

    NARCIS (Netherlands)

    Anbeek, Petronella; Vincken, Koen L.; Groenendaal, Floris; Koeman, Annemieke; Van Osch, Matthias J. P.; Van der Grond, Jeroen

    A fully automated method has been developed for segmentation of four different structures in the neonatal brain: white matter (WM), central gray matter (CEGM), cortical gray matter (COGM), and cerebrospinal fluid (CSF). The segmentation algorithm is based on information from T2-weighted (T2-w) and

  17. Automatic Analysis of Brain Tissue and Structural Connectivity in MRI

    NARCIS (Netherlands)

    R. de Boer (Renske)

    2011-01-01

    textabstractStudies of the brain using magnetic resonance imaging (MRI) can provide insights in physiology and pathology that can eventually aid clinical diagnosis and therapy monitoring. MRI data acquired in these studies can be difficult, as well as laborious, to interpret and analyze by

  18. Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research.

    Science.gov (United States)

    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.

  19. Biological fiducial point based registration for multiple brain tissues reconstructed from different imaging modalities

    Science.gov (United States)

    Wu, Huiqun; Zhou, Gangping; Geng, Xingyun; Zhang, Xiaofeng; Jiang, Kui; Tang, Lemin; Zhou, Guomin; Dong, Jiancheng

    2013-10-01

    With the development of computer aided navigation system, more and more tissues shall be reconstructed to provide more useful information for surgical pathway planning. In this study, we aimed to propose a registration framework for different reconstructed tissues from multi-modalities based on some fiducial points on lateral ventricles. A male patient with brain lesion was admitted and his brain scans were performed by different modalities. Then, the different brain tissues were segmented in different modality with relevant suitable algorithms. Marching cubes were calculated for three dimensional reconstructions, and then the rendered tissues were imported to a common coordinate system for registration. Four pairs of fiducial markers were selected to calculate the rotation and translation matrix using least-square measure method. The registration results were satisfied in a glioblastoma surgery planning as it provides the spatial relationship between tumors and surrounding fibers as well as vessels. Hence, our framework is of potential value for clinicians to plan surgery.

  20. Tom Gibson, Plastic Surgeon (1915-93): Allograft rejection by the immune system and prediction of free tissue transplantation.

    Science.gov (United States)

    Conway, H; Reid, W H; Beaton, J J; McGrouther, D A

    2012-11-01

    Tom Gibson made enormous contributions to the modern development of Plastic and Reconstructive Surgery. His key 1943 paper 'The fate of skin homografts in man' described the 'second set' phenomenon attributing graft rejection to an immunological phenomenon. Later in his career he visualised the concept of microvascular tissue transplantation and inspired many young surgeons through his various roles of Director of the unit at Canniesburn Hospital, Professor of Bioengineering and President of the Royal College of Physicians and Surgeons of Glasgow. Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  1. Regeneration of skull bones in adult rabbits after implantation of commercial osteoinductive materials and transplantation of a tissue-engineering construct.

    Science.gov (United States)

    Volkov, A V; Alekseeva, I S; Kulakov, A A; Gol'dshtein, D V; Shustrov, S A; Shuraev, A I; Arutyunyan, I V; Bukharova, T B; Rzhaninova, A A; Bol'shakova, G B; Grigor'yan, A S

    2010-10-01

    We performed a comparative study of reparative osteogenesis in rabbits with experimental critical defects of the parietal bones after implantation of commercial osteoinductive materials "Biomatrix", "Osteomatrix", "BioOss" in combination with platelet-rich plasma and transplantation of a tissue-engineering construct on the basis of autogenic multipotent stromal cells from the adipose tissue predifferentiated in osteogenic direction. It was found that experimental reparative osteogenesis is insufficiently stimulated by implantation materials and full-thickness trepanation holes were not completely closed. After transplantation of the studied tissue-engineering construct, the defect was filled with full-length bone regenerate (in the center of the regenerate and from the maternal bone) in contrast to control and reference groups, where the bone tissue was formed only on the side of the maternal bone. On day 120 after transplantation of the tissue-engineering construct, the percent of newly-formed bone tissue in the regenerate was 24% (the total percent of bone tissue in the regenerate was 39%), which attested to active incomplete regenerative process in contrast to control and reference groups. Thus, the study demonstrated effective regeneration of the critical defects of the parietal bones in rabbits 120 days after transplantation of the tissue-engineering construct in contrast to commercial osteoplastic materials for directed bone regeneration.

  2. Histological advantages of the tumor graft: a murine model involving transplantation of human pancreatic cancer tissue fragments.

    Science.gov (United States)

    Akashi, Yoshimasa; Oda, Tatsuya; Ohara, Yusuke; Miyamoto, Ryoichi; Hashimoto, Shinji; Enomoto, Tsuyoshi; Yamada, Keiichi; Kobayashi, Akihiko; Fukunaga, Kiyoshi; Ohkochi, Nobuhiro

    2013-11-01

    Experimental data based on cell line-derived xenograft models (cell xenograft) seldom reproduce the clinical situation, and therefore we demonstrated here the superiority of a murine model involving transplantation of human pancreatic cancer tissue fragments (tumor graft), focusing on the histological features and drug delivery characteristics. Tumor pieces from 10 pancreatic cancer patients were transplanted into SCID (severe combined immunodeficient) mice. Histological characteristics of tumor grafts, including morphology, desmoplastic reaction, and vascularization, were compared with those of cell xenografts. Drug delivery was evaluated by quantifying the concentrations of injected drug, and the results were compared with its histological features. Eight of the 10 transplanted tumors successfully engrafted. Histological comparisons between tumor grafts and cell xenografts revealed the following: the amount of stroma was more (22.9% ± 11.8% vs 10.8% ± 5.4%; P cancer cell distance was longer (35.3 ± 39.0 vs 3.9 ± 3.1 μm; P Pancreatic tumor grafts better reproduce the histological nature of clinical cancer and thus provide a more realistic model that is applicable for pharmacokinetic studies.

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

    Science.gov (United States)

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

    2013-01-01

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

  4. Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, cancer, and transplantation assessments

    Science.gov (United States)

    Sun, Kun; Jiang, Peiyong; Chan, K. C. Allen; Wong, John; Cheng, Yvonne K. Y.; Liang, Raymond H. S.; Chan, Wai-kong; Ma, Edmond S. K.; Chan, Stephen L.; Cheng, Suk Hang; Chan, Rebecca W. Y.; Tong, Yu K.; Ng, Simon S. M.; Wong, Raymond S. M.; Hui, David S. C.; Leung, Tse Ngong; Leung, Tak Y.; Lai, Paul B. S.; Chiu, Rossa W. K.; Lo, Yuk Ming Dennis

    2015-01-01

    Plasma consists of DNA released from multiple tissues within the body. Using genome-wide bisulfite sequencing of plasma DNA and deconvolution of the sequencing data with reference to methylation profiles of different tissues, we developed a general approach for studying the major tissue contributors to the circulating DNA pool. We tested this method in pregnant women, patients with hepatocellular carcinoma, and subjects following bone marrow and liver transplantation. In most subjects, white blood cells were the predominant contributors to the circulating DNA pool. The placental contributions in the plasma of pregnant women correlated with the proportional contributions as revealed by fetal-specific genetic markers. The graft-derived contributions to the plasma in the transplant recipients correlated with those determined using donor-specific genetic markers. Patients with hepatocellular carcinoma showed elevated plasma DNA contributions from the liver, which correlated with measurements made using tumor-associated copy number aberrations. In hepatocellular carcinoma patients and in pregnant women exhibiting copy number aberrations in plasma, comparison of methylation deconvolution results using genomic regions with different copy number status pinpointed the tissue type responsible for the aberrations. In a pregnant woman diagnosed as having follicular lymphoma during pregnancy, methylation deconvolution indicated a grossly elevated contribution from B cells into the plasma DNA pool and localized B cells as the origin of the copy number aberrations observed in plasma. This method may serve as a powerful tool for assessing a wide range of physiological and pathological conditions based on the identification of perturbed proportional contributions of different tissues into plasma. PMID:26392541

  5. Automatic Analysis of Brain Tissue and Structural Connectivity in MRI

    OpenAIRE

    Boer, Renske

    2011-01-01

    textabstractStudies of the brain using magnetic resonance imaging (MRI) can provide insights in physiology and pathology that can eventually aid clinical diagnosis and therapy monitoring. MRI data acquired in these studies can be difficult, as well as laborious, to interpret and analyze by human observers. Moreover, analysis by human observers can hamper the reproducibility by both inter- and intra-observer variability. These studies do, therefore, require accurate and reproducible quantitati...

  6. Brain tissue modifications induced by cholinergic therapy in Alzheimer's disease.

    Science.gov (United States)

    Bozzali, Marco; Parker, Geoff J M; Spanò, Barbara; Serra, Laura; Giulietti, Giovanni; Perri, Roberta; Magnani, Giuseppe; Marra, Camillo; G Vita, Maria; Caltagirone, Carlo; Cercignani, Mara

    2013-12-01

    A previous preliminary investigation based on a novel MRI approach to map anatomical connectivity revealed areas of increased connectivity in Alzheimer's disease (AD) but not in mild cognitive impairment patients. This prompted the hypothesis tested here, that these areas might reflect phenomena of brain plasticity driven by acetylcholinesterase inhibitors (AChEIs). Thirty-eight patients with probable AD (19 under medication with AChEIs and 19 drug-naïve) were recruited together with 11 healthy controls. All subjects had MRI scanning at 3T, including volumetric and diffusion-weighted scans. Probabilistic tractography was used to initiate streamlines from all parenchymal voxels, and anatomical connectivity maps (ACMs) were obtained by counting, among the total number of streamlines initiated, the fraction passing through each brain voxel. After normalization into standard space, ACMs were used to test for between-group comparisons, and for interactions between the exposure to AChEIs and global level of cognition. Patients with AD had reduced ACM values in the fornix, cingulum, and supramarginal gyri. The ACM value was strongly associated with the AChEI dosage-x-duration product in the anterior limb (non-motor pathway) of the internal capsule. Tractography from this region identified the anterior thalamic radiation as the main white matter (WM) tract passing through it. The reduced connectivity in WM bundles connecting the hippocampi with the rest of the brain (fornix/cingulum) suggests a possible mechanism for the spread of AD pathology. An intriguing explanation for the interaction between AChEIs and ACM is related to the mechanisms of brain plasticity, partially driven by neurotrophic properties of acetylcholine replacement. Copyright © 2012 Wiley Periodicals, Inc.

  7. Extraction of optical properties and prediction of light distribution in rat brain tissue.

    Science.gov (United States)

    Azimipour, Mehdi; Baumgartner, Ryan; Liu, Yuming; Jacques, Steven L; Eliceiri, Kevin; Pashaie, Ramin

    2014-01-01

    Predicting the distribution of light inside any turbid media, such as biological tissue, requires detailed information about the optical properties of the medium, including the absorption and scattering coefficients and the anisotropy factor. Particularly, in biophotonic applications where photons directly interact with the tissue, this information translates to system design optimization, precision in light delivery, and minimization of unintended consequences, such as phototoxicity or photobleaching. In recent years, optogenetics has opened up a new area in deep brain stimulation with light and the method is widely adapted by researchers for the study of the brain circuitries and the dynamics of neurological disorders. A key factor for a successful optogenetic stimulation is delivering an adequate amount of light to the targeted brain objects. The adequate amount of light needed to stimulate each brain object is identified by the tissue optical properties as well as the type of opsin expressed in the tissue, wavelength of the light, and the physical dimensions of the targeted area. Therefore, to implement a precise light delivery system for optogenetics, detailed information about the optical properties of the brain tissue and a mathematical model that incorporates all determining factors is needed to find a good estimation of light distribution in the brain. In general, three measurements are required to obtain the optical properties of any tissue, namely diffuse transmitted light, diffuse reflected light, and transmitted ballistic beam. In this report, these parameters were measured in vitro using intact rat brain slices of 500 μm thickness via a two-integrating spheres optical setup. Then, an inverse adding doubling method was used to extract the optical properties of the tissue from the collected data. These experiments were repeated to cover the whole brain tissue with high spatial resolution for the three different cuts (transverse, sagittal, and coronal

  8. Cell and tissue kinetics of the subependymal layer in mouse brain following heavy charged particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Manley, N.B.; Fabrikant, J.I.; Alpen, E.L.

    1988-12-01

    The following studies investigate the cellular response and cell population kinetics of the subependymal layer in the mouse brain exposed to heavy charged particle irradiation. Partial brain irradiation with helium and neon ions was confined to one cortex of the brain. Both the irradiated and the unirradiated contralateral cortex showed similar disturbances of the cell and tissue kinetics in the subependymal layers. The irradiated hemisphere exhibited histological damage, whereas the unirradiated side appeared normal histologically. This study concerns the cell population and cell cycle kinetics of the subependymal layer in the mouse brain, and the effects of charged particle irradiations on this cell population. Quantitative high resolution autoradiography was used to study the kinetic parameters in this cell layer. This study should help in understanding the effects of these high-energy heavy ions on normal mammalian brain tissue. The response of the mammalian brain exposure to charged particle ionizing radiation may be extremely variable. It varies from minimal physiological changes to overt tissue necrosis depending on a number of factors such as: the administered dose, dose-rate, the volume of the irradiated tissue, and the biological end-point being examined.

  9. Disseminated Soft Tissue Infection and Sepsis with Stenotrophomonas maltophilia in a Bone Marrow Transplant Patient

    Directory of Open Access Journals (Sweden)

    Jeffrey H Lipton

    1996-01-01

    Full Text Available A 32-year-old female presented with aplastic anemia and subsequently underwent a one-antigen mismatched bone marrow transplant from her brother. She failed to engraft and a second graft was attempted. Protracted neutropenia of three months’ duration despite the use of broad spectrum antibiotics occurred. Stenotrophomonas (Xanthomonas maltophilia metastatic cellulitis developed that did not respond to appropriate antibiotics.

  10. Limb Ischemia after Heart Transplantation: An Unusual Case of Tissue Embolism

    Directory of Open Access Journals (Sweden)

    Seyed Mohsen Mirhosseini

    2017-05-01

    Full Text Available Major complications of heart transplantation include graft rejection, infection, graft arteriosclerosis, malignancy, and drug toxicity. Among these complications, infections and thrombophilic disorders are of particular interest owing to their major contribution to morbidity and mortality among heart transplantation patients. Thrombophilic disorders are caused by imbalance between hypercoagulation and fibrinolytic states. In this report, we describe a 43-year-old man who had unusual complications of heart transplantation. We presume that the unusual postoperative complications of the patient might have been caused by a faulty surgical procedure, improper use of anticoagulant agents, and incomplete prophylaxis for infections. During the postoperative period, the patient suffered arterial obstruction three times, for which he underwent clot removal via embolectomy. In addition to arterial obstruction, the patient had a mobile mass in the left atrium that was removed by open cardiac surgery. The frozen sample of the cardiac mass was positive for Acinetobacter baumannii. After 7 days of observation in the hospital and proper antibiotic regimen, the patient was sent home with no additional complaints and normal physical examination. We conclude that in heart transplantation patients, the precise performance of the surgical procedure, postoperative care, and early removal of the embolus might reduce morbidities and mortality due to thrombophilic disorders.

  11. Trace element determinations in brain tissues from normal and clinically demented individuals

    Energy Technology Data Exchange (ETDEWEB)

    Saiki, Mitiko; Genezini, Frederico A., E-mail: mitiko@ipen.br, E-mail: fredzini@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro do Reator de Pesquisas; Leite, Renata E.P.; Grinberg, Lea T.; Ferretti, Renata E.L.; Suemoto, Claudia; Pasqualucci, Carlos A.; Jacob-Filho, Wilson, E-mail: renataleite@usp.br, E-mail: lea@grinberg.com.br, E-mail: reloah@usp.br, E-mail: farfel@usp.br, E-mail: csuemoto@gmail.com, E-mail: cpasqua@usp.br, E-mail: wijac@usp.br [Universidade de Sao Paulo (FM/USP), Sao Paulo, SP (Brazil). Fac. de Medicina

    2013-07-01

    Studies on trace element levels in human brains under normal and pathological conditions have indicated a possible correlation between some trace element concentrations and neurodegenerative diseases. In this study, analysis of brain tissues was carried out to investigate if there are any differences in elemental concentrations between brain tissues from a normal population above 50 years of age presenting Clinical Dementia Rating (CDR) equal to zero (CDR=0) and that cognitively affected population ( CDR=3). The tissues were dissected, ground, freeze-dried and then analyzed by instrumental neutron activation analysis. Samples and elemental standards were irradiated in a neutron flux at the IEA-R1 nuclear research reactor for Br, Fe, K, Na, Rb, Se and Zn determinations. The induced gamma ray activities were measured using a hyperpure Ge detector coupled to a gamma ray spectrometer. The one-way ANOVA test (p< 0.05) was used to compare the results. All the elements determined in the hippocampus brain region presented differences between the groups presenting CDR=0 and CDR=3. In the case of frontal region only the elements Na, Rb and Zn showed differences between these two groups. These findings proved the correlation between elemental levels present in brain tissues neurodegenerative diseases. Biological standard reference materials SRM 1566b Oyster Tissue and SRM 1577b Bovine Liver analyzed for quality control indicated good accuracy and precision of the results. (author)

  12. Long-term changes in the material properties of brain tissue at the implant-tissue interface

    Science.gov (United States)

    Sridharan, Arati; Rajan, Subramaniam D.; Muthuswamy, Jit

    2013-12-01

    Objective. Brain tissue undergoes dramatic molecular and cellular remodeling at the implant-tissue interface that evolves over a period of weeks after implantation. The biomechanical impact of such remodeling on the interface remains unknown. In this study, we aim to assess the changes in the mechanical properties of the brain-electrode interface after chronic implantation of a microelectrode. Approach. Microelectrodes were implanted in the rodent cortex at a depth of 1 mm for different durations—1 day (n = 4), 10-14 days (n = 4), 4 weeks (n = 4) and 6-8 weeks (n = 7). After the initial duration of implantation, the microelectrodes were moved an additional 1 mm downward at a constant speed of 10 µm s-1. Forces experienced by the microelectrode were measured during movement and after termination of movement. The biomechanical properties of the interfacial brain tissue were assessed from measured force-displacement curves using two separate models—a two-parameter Mooney-Rivlin hyperelastic model and a viscoelastic model with a second-order Prony series. Main results. Estimated shear moduli using a second-order viscoelastic model increased from 0.5-2.6 kPa (day 1 of implantation) to 25.7-59.3 kPa (after 4 weeks of implantation) and subsequently decreased to 0.8-7.9 kPa after 6-8 weeks of implantation in 6 of the 7 animals. The estimated elastic modulus increased from 4.1-7.8 kPa on the day of implantation to 24-44.9 kPa after 4 weeks. The elastic modulus was estimated to be 6.8-33.3 kPa in 6 of the 7 animals after 6-8 weeks of implantation. The above estimates suggest that the brain tissue surrounding the microelectrode evolves from a stiff matrix with maximal shear and elastic modulus after 4 weeks of implantation into a composite of two different layers with different mechanical properties—a stiff compact inner layer surrounded by softer brain tissue that is biomechanically similar to brain tissue—during the first week of implantation. Tissue micromotion

  13. Adaptive online learning based tissue segmentation of MR brain images

    NARCIS (Netherlands)

    Damkat, C.

    2007-01-01

    The aging population in the European Union and the US has increased the importance of research in neurodegenerative diseases. Imaging plays an essential role in this endeavor by providing insight to the intricate cellular and inter-cellular processes in living tissues that will otherwise be

  14. The brain modulates insulin sensitivity in multiple tissues

    NARCIS (Netherlands)

    Parlevliet, Edwin T.; Coomans, Claudia P.; Rensen, Patrick C. N.; Romijn, Johannes A.

    2014-01-01

    Insulin sensitivity is determined by direct effects of circulating insulin on metabolically active tissues in combination with indirect effects of circulating insulin, i.e. via the central nervous system. The dose-response effects of insulin differ between the various physiological effects of

  15. Optical clearing and fluorescence deep-tissue imaging for 3D quantitative analysis of the brain tumor microenvironment.

    Science.gov (United States)

    Lagerweij, Tonny; Dusoswa, Sophie A; Negrean, Adrian; Hendrikx, Esther M L; de Vries, Helga E; Kole, Jeroen; Garcia-Vallejo, Juan J; Mansvelder, Huibert D; Vandertop, W Peter; Noske, David P; Tannous, Bakhos A; Musters, René J P; van Kooyk, Yvette; Wesseling, Pieter; Zhao, Xi Wen; Wurdinger, Thomas

    2017-11-01

    Three-dimensional visualization of the brain vasculature and its interactions with surrounding cells may shed light on diseases where aberrant microvascular organization is involved, including glioblastoma (GBM). Intravital confocal imaging allows 3D visualization of microvascular structures and migration of cells in the brain of mice, however, with limited imaging depth. To enable comprehensive analysis of GBM and the brain microenvironment, in-depth 3D imaging methods are needed. Here, we employed methods for optical tissue clearing prior to 3D microscopy to visualize the brain microvasculature and routes of invasion of GBM cells. We present a workflow for ex vivo imaging of optically cleared brain tumor tissues and subsequent computational modeling. This workflow was used for quantification of the microvasculature in relation to nuclear or cellular density in healthy mouse brain tissues and in human orthotopic, infiltrative GBM8 and E98 glioblastoma models. Ex vivo cleared mouse brain tissues had a >10-fold imaging depth as compared to intravital imaging of mouse brain in vivo. Imaging of optically cleared brain tissue allowed quantification of the 3D microvascular characteristics in healthy mouse brains and in tissues with diffuse, infiltrative growing GBM8 brain tumors. Detailed 3D visualization revealed the organization of tumor cells relative to the vasculature, in both gray matter and white matter regions, and patterns of multicellular GBM networks collectively invading the brain parenchyma. Optical tissue clearing opens new avenues for combined quantitative and 3D microscopic analysis of the topographical relationship between GBM cells and their microenvironment.

  16. Dynamic gadolinium uptake in thermally treated canine brain tissue and experimental cerebral tumors.

    Science.gov (United States)

    Kangasniemi, Marko; Stafford, R Jason; Price, Roger E; Jackson, Edward F; Hazle, John D

    2003-02-01

    Thermal coagulation of cerebral tumors induces reactive changes within adjacent brain tissue, which appear as Gd-DTPA enhancement in MR images. This makes assessment of therapeutic success difficult to establish radiographically because the reactive changes can mimic residual tumor. Dynamic Gd-DTPA uptake curves in reactive tissue and tumor were investigated to assess the utility of contrast enhanced (CE)-dynamic MRI to distinguish reactive changes from residual tumor in a canine model. Cerebral thermal necrosis was induced using a 980 nm laser in 11 dogs with intracerebral transmissible venereal tumors (TVTs). A fast spin-echo T1-weighted imaging sequence was used for CE-dynamic MRI. Gd-DTPA uptake data were acquired with 10-second temporal resolution and for untreated TVTs for reactive tissue using a sigmoidal-exponential model. Characteristic gadolinium uptake curves were measured and characterized for reactive brain tissue, and untreated and treated TVTs. Both early and delayed dynamic responses were significantly different in reactive brain tissue compared with TVT. Reactive thermal changes in otherwise normal brain tissue can be distinguished from residual tumor after cerebral thermal therapy using CE-dynamic MRI.

  17. Transplantation of human fetal blood stem cells in the osteogenesis imperfecta mouse leads to improvement in multiscale tissue properties.

    Science.gov (United States)

    Vanleene, Maximilien; Saldanha, Zahraa; Cloyd, Kristy L; Jell, Gavin; Bou-Gharios, George; Bassett, J H Duncan; Williams, Graham R; Fisk, Nicholas M; Oyen, Michelle L; Stevens, Molly M; Guillot, Pascale V; Shefelbine, Sandra J

    2011-01-20

    Osteogenesis imperfecta (OI or brittle bone disease) is a disorder of connective tissues caused by mutations in the collagen genes. We previously showed that intrauterine transplantation of human blood fetal stem/stromal cells in OI mice (oim) resulted in a significant reduction of bone fracture. This work examines the cellular mechanisms and mechanical bone modifications underlying these therapeutic effects, particularly examining the direct effects of donor collagen expression on bone material properties. In this study, we found an 84% reduction in femoral fractures in transplanted oim mice. Fetal blood stem/stromal cells engrafted in bones, differentiated into mature osteoblasts, expressed osteocalcin, and produced COL1a2 protein, which is absent in oim mice. The presence of normal collagen decreased hydroxyproline content in bones, altered the apatite crystal structure, increased the bone matrix stiffness, and reduced bone brittleness. In conclusion, expression of normal collagen from mature osteoblast of donor origin significantly decreased bone brittleness by improving the mechanical integrity of the bone at the molecular, tissue, and whole bone levels.

  18. Accuracy and safety verification of ovarian reserve assessment technique for ovarian tissue transplantation using optical coherence tomography in mice ovary

    Science.gov (United States)

    Takae, Seido; Tsukada, Kosuke; Sato, Yorino; Okamoto, Naoki; Kawahara, Tai; Suzuki, Nao

    2017-03-01

    Except for histological study, there are currently no suitable techniques available for the detection and identification of primordial follicles in ovary of primary ovarian insufficiency patients who have undetectable AMH levels. Also, the ability to locate and quantify follicles on ovarian cortex strips, without fixation, is valuable for patients who could undergo subsequent successful ovarian tissue transplantation. Although optical coherence tomography (OCT) is a well-established high resolution imaging technique without fixation commonly applied in biomedicine, few reports are available on ovarian tissue imaging. In present study, we established standard OCT follicle images at each developmental stage, including the primordial follicle, and demonstrated the efficacy of OCT to estimate IVF outcome in transplanted mice ovary like ovarian reserve tests. Unfortunately, the current commercial OCT could not be used to accurate follicle count the number of follicles for whole ovary, because the maximum depth of examination was 100 μm. And we demonstrated the safety of OCT examination, it did not affect IVF outcome and birth defect rate, and reproductive ability. Although there is room for improvement, these findings will be first step to bring OCT examination a step closer to clinical application for measuring true ovarian reserve and localizing follicles.

  19. Transplantation of Autologous Minced Bladder Mucosa for a One-Step Reconstruction of a Tissue Engineered Bladder Conduit

    Directory of Open Access Journals (Sweden)

    Gisela Reinfeldt Engberg

    2013-01-01

    Full Text Available Surgical intervention is sometimes needed to create a conduit from the abdominal wall to the bladder for self-catheterization. We developed a method for tissue engineering a conduit for bladder emptying without in vitro cell culturing as a one-step procedure. In a porcine animal model bladder, wall tissue was excised and the mucosa was minced to small particles. The particles were attached to a tube in a 1 : 3 expansion rate with fibrin glue and transplanted back by attaching the tube to the bladder and through the abdominal wall. Sham served as controls. After 4-5 weeks, conduits were assessed in respect to macroscopic and microscopic appearance in 6 pigs. Two pigs underwent radiology before termination. Gross examination revealed a patent conduit with an opening to the bladder. Histology and immunostaining showed a multilayered transitional uroepithelium in all cases. Up to 89% of the luminal surface area was neoepithelialized but with a loose attachment to the submucosa. No epithelium was found in control animals. CT imaging revealed a patent channel that could be used for filling and emptying the bladder. Animals that experienced surgical complications did not form conduits. Minced autologous bladder mucosa can be transplanted around a tubular mold to create a conduit to the urinary bladder without in vitro culturing.

  20. Effects of fluid dynamic stress on fracturing of cell-aggregated tissue during purification for islets of Langerhans transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Shintaku, H; Kawano, S [Department of Mechanical Science and Bioengineering, Graduate School of Engineering Science, Osaka University, Machikaneyama-cho, Toyonaka, Osaka 560-8531 (Japan); Okitsu, T [Transplantation Unit, Kyoto University Hospital, Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Matsumoto, S [Baylor Research Institute Islet Cell Laboratory, 1400 Eight Avenue, Fort Worth, TX 76104 (United States); Suzuki, T; Kanno, I; Kotera, H [Department of Microengineering, Kyoto University, Yoshida-Honmachi, Sakyo-ku, Kyoto 606-8501 (Japan)], E-mail: shintaku@me.es.osaka-u.ac.jp

    2008-06-07

    Among clinical treatments for type 1 diabetes mellitus, the transplantation of islets of Langerhans to the portal vein of the hepar is a commonly used treatment for glucose homeostasis. Islet purification using the density gradient of a solution in a centrifuge separator is required for safety and efficiency. In the purification, the number of tissues to be transplanted is reduced by removing the acinar tissue and gathering the islet from the digest of pancreas. However, the mechanical effects on the fracture of islets in the centrifuge due to fluid dynamic stress are a serious problem in the purification process. In this study, a preliminary experiment using a cylindrical rotating viscometer with a simple geometry is conducted in order to systematically clarify the effect of fluid dynamic stress on the fracture of islets. The effects of fluid dynamic stress on the islet configuration is quantitatively measured for various flow conditions, and a predictive fracture model is developed based on the experimental results. Furthermore, in the practical purification process in the COBE (Gambro BCT), which is widely used in clinical applications, we perform a numerical analysis of the fluid dynamic stress based on Navier-Stokes equations to estimate the stress conditions for islets. Using the fracture model and numerical analysis, the islet fracture characteristics using the COBE are successfully investigated. The results obtained in this study provide crucial information for the purification of islets by centrifuge in practical and clinical applications.

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

    Science.gov (United States)

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

    2009-05-01

    This research investigated the feasibility of using time-dependent diffuse reflectance spectroscopy to differentiate pediatric epileptic brain tissue from normal brain tissue. The optical spectroscopic technique monitored the dynamic optical properties of the cerebral cortex that are associated with its physiological, morphological, and compositional characteristics. Due to the transient irregular epileptic discharge activity within the epileptic brain tissue it was hypothesized that the lesion would express abnormal dynamic optical behavior that would alter normal dynamic behavior. Thirteen pediatric epilepsy patients and seven pediatric brain tumor patients (normal controls) were recruited for this clinical study. Dynamic optical properties were obtained from the cortical surface intraoperatively using a timedependent diffuse reflectance spectroscopy system. This system consisted of a fiber-optic probe, a tungsten-halogen light source, and a spectrophotometer. It acquired diffuse reflectance spectra with a spectral range of 204 nm to 932 nm at a rate of 33 spectra per second for approximately 12 seconds. Biopsy samples were taken from electrophysiologically abnormal cortex and evaluated by a neuropathologist, which served as a gold standard for lesion classification. For data analysis, spectral intensity changes of diffuse reflectance in the time domain at two different wavelengths from each investigated site were compared. Negative correlation segment, defined by the periods where the intensity changes at the two wavelengths were opposite in their slope polarity, were extracted. The total duration of negative correlation, referred to as the "negative correlation time index", was calculated by integrating the negative correlation segments. The negative correlation time indices from all investigated sites were sub-grouped according to the corresponding histological classifications. The difference between the mean indices of two subgroups was evaluated by standard

  2. Gene Expression Profiling during Pregnancy in Rat Brain Tissue

    Directory of Open Access Journals (Sweden)

    Phyllis E. Mann

    2014-03-01

    Full Text Available The neurophysiological changes that occur during pregnancy in the female mammal have led to the coining of the phrases “expectant brain” and “maternal brain”. Although much is known of the hormonal changes during pregnancy, alterations in neurotransmitter gene expression have not been well-studied. We examined gene expression in the ventromedial nucleus of the hypothalamus (VMH during pregnancy based on the fact that this nucleus not only modulates the physiological changes that occur during pregnancy but is also involved in the development of maternal behavior. This study was designed to identify genes that are differentially expressed between mid- and late-pregnancy in order to determine which genes may be associated with the onset and display of maternal behavior and the development of the maternal brain. A commercially available PCR array containing 84 neurotransmitter receptor and regulator genes (RT2 Profiler PCR array was used. Brains were harvested from rats on days 12 and 21 of gestation, frozen, and micropunched to obtain the VMH. Total RNA was extracted, cDNA prepared, and SYBR Green qPCR was performed. In the VMH, expression of five genes were reduced on day 21 of gestation compared to day 12 (Chrna6, Drd5, Gabrr2, Prokr2, and Ppyr1 whereas Chat, Chrm5, Drd4, Gabra5, Gabrg2, LOC289606, Nmu5r2, and Npy5r expression was elevated. Five genes were chosen to be validated in an additional experiment based on their known involvement in maternal behavior onset. This experiment confirmed that gene expression for both the CCK-A receptor and the GABAAR γ2 receptor increases at the end of pregnancy. In general, these results identify genes possibly involved in the establishment of the maternal brain in rats and indicate possible new genes to be investigated.

  3. A longitudinal study of the mechanical properties of injured brain tissue in a mouse model.

    Science.gov (United States)

    Feng, Yuan; Gao, Yuan; Wang, Tao; Tao, Luyang; Qiu, Suhao; Zhao, Xuefeng

    2017-07-01

    Mechanical properties of brain tissue are crucial to understand the mechanism of traumatic brain injury (TBI). Over the past several decades, most of the studies focused on healthy brain tissues, while few of them are about the injured tissues. Therefore, limited knowledge is known about the mechanical properties of the injured brain tissues. In this study, we used an in vivo mouse model with a weight drop device to study injured brain tissues. Around the injury site, mechanical properties of the injured, neighboring, and the corresponding contralateral regions of interest (ROIs) were measured over five temporal points by indentation. Longitudinal and regional comparisons of the mechanical properties revealed that the ROI of the injured tissue had a higher elastic modulus than the contralateral counterpart one-hour post-injury. However, the elastic modulus decreased one-day post-injury and recovered to be close to the contralateral ROI in 7 days. The elastic modulus curves of the injured and the contralateral counterpart ROIs crossed at time points of 12h and 1 day post-injury, where two significant increases of glial fibrillary acidic protein (GFAP) positive cells were observed. Biological staining results indicated that both the astrocytic responses and the morphological structure could affect the mechanical properties of the injured tissue. The observed longitudinal changes of the mechanical properties at the tissue level and the morphological and biological changes at the cellular level provide insights into understanding the mechanism of TBI. Results are also meaningful for applying emerging in vivo diagnostic tools such as magnetic resonance elastography (MRE) in TBI detection. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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

  5. Three-dimensional structure of brain tissue at submicrometer resolution

    Energy Technology Data Exchange (ETDEWEB)

    Saiga, Rino; Mizutani, Ryuta, E-mail: ryuta@tokai-u.jp [Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292 (Japan); Inomoto, Chie; Takekoshi, Susumu; Nakamura, Naoya; Tsuboi, Akio; Osawa, Motoki [Tokai University School of Medicine, Isehara, Kanagawa 259-1193 (Japan); Arai, Makoto; Oshima, Kenichi; Itokawa, Masanari [Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506 (Japan); Uesugi, Kentaro; Takeuchi, Akihisa; Terada, Yasuko; Suzuki, Yoshio [Japan Synchrotron Radiation Research Institute (JASRI/SPring-8), Sayo, Hyogo 679-5198 (Japan)

    2016-01-28

    Biological objects are composed of submicrometer structures such as cells and organelles that are essential for their functions. Here, we report on three-dimensional X-ray visualization of cells and organelles at resolutions up to 100 nm by imaging microtomography (micro-CT) equipped with Fresnel zone plate optics. Human cerebral tissue, fruit fly cephalic ganglia, and Escherichia coli bacteria labeled with high atomic-number elements were embedded in epoxy resin and subjected to X-ray microtomography at the BL37XU and BL47XU beamlines of the SPring-8 synchrotron radiation facility. The obtained results indicated that soft tissue structures can be visualized with the imaging microtomography.

  6. Investigation on metal elements in the brain tissues from DNTC patients

    Energy Technology Data Exchange (ETDEWEB)

    Ide-Ektessabi, Ari E-mail: h51167@sakura.kudpc.kyoto-u.ac.jp; Kawakami, Takuo; Ishihara, Ryoko; Mizuno, Yutaka; Takeuchi, Tohru

    2004-07-01

    Trace metallic elements in human cells play important roles in various cell functions as metalloprotein, metalloenzyme or metallic ions. Diffuse neurofibrillary tangles with calcification (DNTC) is an atypical dementia and is characterized pathologically by diffuse neurofibrillary tangles without senile plaques. In this study, X-ray fluorescence (XRF) spectroscopy using synchrotron radiation (SR) was applied to determine the distribution and density of the ultra-trace elements in the brain tissues from DTNC patients. This method made it possible to determine trace metallic elements non-destructively. The trace metallic elements (such as Ca, Fe, Zn, and Pb) in the brain tissues were examined. Two-dimension imaging of the elements and relative quantification of the elements in the brains were performed. The lead concentrations were observed in the calcified blood vessel in the brains with DNTC.

  7. Nondestructive recovery and examination of bullet fragments from brain tissue.

    Science.gov (United States)

    Johnson, A C; Kinard, W D; Washington, W D

    1980-04-01

    A technique providing both analytical and toolmark results for lead fragments from bullets is discussed. It permits the nondestructive recovery of bullet fragments from soft cadaver tissue and was used with a plasma asher in an actual homicide case. The lead fragments are examined by neutron activation analysis (but other analytical techniques can be used) for their antimony and arsenic content and by microscopy for matching toolmarks.

  8. Effect of pineapple peel extract on total phospholipids and lipid peroxidation in brain tissues of rats.

    Science.gov (United States)

    Erukainure, O L; Ajiboye, J A; Adejobi, R O; Okafor, O Y; Kosoko, S B; Owolabi, F O

    2011-03-01

    To investigate the ability of the methanolic extract of pineapple peel to attenuate alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues. Oxidative stress was induced by oral administration of ethanol (20% w/v) at a dosage of 5 mL/kg bw in rats. After 28 days of treatment, the rats were fasted overnight and sacrificed by cervical dislocation. Brain tissues were assayed for total phospholipid (TP) content and malondialdehyde (MDA). Administration of alcohol significantly caused a reduction in TP content. Treatment with pineapple peel extract significantly increased the TP content. Significant high levels of MDA was observed in alcohol-fed rats, treatment with pineapple peel extract significantly reduced the MDA levels. Results obtained from this study indicates that pineapple peel extract protects against alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  9. Melatonin attenuated brain death tissue extract-induced cardiac damage by suppressing DAMP signaling.

    Science.gov (United States)

    Sung, Pei-Hsun; Lee, Fan-Yen; Lin, Ling-Chun; Chen, Kuan-Hung; Lin, Hung-Sheng; Shao, Pei-Lin; Li, Yi-Chen; Chen, Yi-Ling; Lin, Kun-Chen; Yuen, Chun-Man; Chang, Hsueh-Wen; Lee, Mel S; Yip, Hon-Kan

    2018-01-09

    We tested the hypothesis that melatonin prevents brain death (BD) tissue extract (BDEX)-induced cardiac damage by suppressing inflammatory damage-associated molecular pattern (DAMP) signaling in rats. Six hours after BD induction, levels of a DAMP component (HMGB1) and inflammatory markers (TLR-2, TLR-4, MYD88, IκB, NF-κB, IL-1β, IFN-γ, TNF-α and IL-6) were higher in brain tissue from BD animals than controls. Levels of HMGB1 and inflammatory markers were higher in BDEX-treated H9C2 cardiac myoblasts than in cells treated with healthy brain tissue extract. These increases were attenuated by melatonin but re-induced with luzindole (all P DAMP inflammatory axis.

  10. Distribution of lead in the brain tissues from DNTC patients using synchrotron radiation microbeams

    Energy Technology Data Exchange (ETDEWEB)

    Ide-Ektessabi, Ari [International Innovation Center, Kyoto University, Kyoto (Japan); Ota, Yukihide [Department of Precision Engineering, Kyoto University, Yoshida Honnmachi, Sakyo-ku, Kyoto (Japan)]. E-mail: h51167@sakura.kudpc.kyoto-u.ac.jp; Ishihara, Ryoko [Department of Psychiatry, Nagoya University, Graduate School of Medicine, Nagoya (Japan); Mizuno, Yutaka [Obu Dementia Care Research and Training Center, Obu (Japan); Takeuchi, Tohru [Department of Psychiatry, Nagoya University, Graduate School of Medicine, Nagoya (Japan)

    2005-12-15

    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.

  11. Analysis of sports related mTBI injuries caused by elastic wave propagation through brain tissue

    Directory of Open Access Journals (Sweden)

    D Case

    2016-10-01

    Full Text Available Repetitive concussions and sub-concussions suffered by athletes have been linked to a series of sequelae ranging from traumatic encephalopathy to dementia pugilistica. A detailed finite element model of the human head was developed based on standard libraries of medical imaging. The model includes realistic material properties for the brain tissue, bone, soft tissue, and CSF, as well as the structure and properties of a protective helmet. Various impact scenarios were studied, with a focus on the strains/stresses and pressure gradients and concentrations created in the brain tissue due to propagation of waves produced by the impact through the complex internal structure of the human head. This approach has the potential to expand our understanding of the mechanism of brain injury, and to better assess the risk of delayed neurological disorders for tens of thousands of young athletes throughout the world.

  12. Blood BDNF concentrations reflect brain-tissue BDNF levels across species

    DEFF Research Database (Denmark)

    Klein, Anders B; Williamson, Rebecca; Santini, Martin A

    2011-01-01

    Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been ...... positive correlation between frontal cortex and hippocampal BDNF levels in mice (r2=0.81, p=0.0139). Our data support the view that measures of blood and plasma BDNF levels reflect brain-tissue BDNF levels....

  13. Quantification of C4d deposition and hepatitis C virus RNA in tissue in cases of graft rejection and hepatitis C recurrence after liver transplantation

    Directory of Open Access Journals (Sweden)

    Alice Tung Wan Song

    2015-02-01

    Full Text Available Histology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+, HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+, acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-. All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection.

  14. A low background Raman probe for optical biopsy of brain tissue

    Science.gov (United States)

    Stevens, Oliver A. C.; Hutchings, Joanne; Gray, William; Day, John C.

    2014-03-01

    Removal of intrinsic brain tumours is a delicate process, where a high degree of specificity is required to remove all of the tumour tissue without damaging healthy brain. The accuracy of this process can be greatly enhanced by intraoperative guidance. Optical biopsies using Raman spectroscopy are a minimally invasive and lower cost alternative to current guidance methods. A miniature Raman probe for performing optical biopsies of human brain tissue is presented. The probe allows sampling inside a conventional stereotactic brain biopsy system: a needle of length 200mm and inner diameter of 1.8mm. The probe achieves a very low fluorescent background whilst maintaining good collection of Raman signal by employing a miniature stand-off Raman design. To illustrate this, the probe is compared with a Raman probe that uses a pair of optical fibres for collection. The miniature stand-off Raman probe is shown to collect a comparable number of Raman scattered photons, but the fluorescence caused by silica fibres in a Raman needle probe is reduced by a factor of two for Raman shifts under 500 cm-1, and by 30% at 600-700 cm-1. In addition, this design contains only medically approved materials at the distal end. The probe's suitability for use on tissue is demonstrated by discriminating between different types of porcine brain tissue.

  15. Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder

    Directory of Open Access Journals (Sweden)

    Guangjun Zhao

    2016-01-01

    Full Text Available 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.

  16. Neurosurgical sapphire handheld probe for intraoperative optical diagnostics, laser coagulation and aspiration of malignant brain tissue

    Science.gov (United States)

    Shikunova, Irina A.; Zaytsev, Kirill I.; Stryukov, Dmitrii O.; Dubyanskaya, Evgenia N.; Kurlov, Vladimir N.

    2017-07-01

    In this paper, a handheld contact probe based on sapphire shaped crystal was developed for the intraoperative optical diagnosis and aspiration of malignant brain tissue combined with the laser hemostasis. Such a favorable combination of several functions in a single instrument significantly increases its clinical relevance. It makes possible highly-accurate real-time detection and removal of either large-scale malignancies or even separate invasive cancer cells. The proposed neuroprobe was integrated into the clinical neurosurgical workflow for the intraoperative fluorescence identification and removal of malignant tissues of the brain.

  17. Microsensors for in vivo Measurement of Glutamate in Brain Tissue

    Directory of Open Access Journals (Sweden)

    Miranda van der Zeyden

    2008-11-01

    Full Text Available Several immobilized enzyme-based electrochemical biosensors for glutamate detection have been developed over the last decade. In this review, we compare first and second generation sensors. Structures, working mechanisms, interference prevention, in vitro detection characteristics and in vivo performance are summarized here for those sensors that have successfully detected brain glutamate in vivo. In brief, first generation sensors have a simpler structure and are faster in glutamate detection. They also show a better sensitivity to glutamate during calibration in vitro. For second generation sensors, besides their less precise detection, their fabrication is difficult to reproduce, even with a semi-automatic dip-coater. Both generations of sensors can detect glutamate levels in vivo, but the reported basal levels are different. In general, second generation sensors detect higher basal levels of glutamate compared with the results obtained from first generation sensors. However, whether the detected glutamate is indeed from synaptic sources is an issue that needs further attention.

  18. Low-frequency dielectric dispersion of brain tissue due to electrically long neurites

    Science.gov (United States)

    Monai, Hiromu; Inoue, Masashi; Miyakawa, Hiroyoshi; Aonishi, Toru

    2012-12-01

    The dielectric properties of brain tissue are important for understanding how neural activity is related to local field potentials and electroencephalograms. It is known that the permittivity of brain tissue exhibits strong frequency dependence (dispersion) and that the permittivity is very large in the low-frequency region. However, little is known with regard to the cause of the large permittivity in the low-frequency region. Here, we postulate that the dielectric properties of brain tissue can be partially accounted for by assuming that neurites are of sufficient length to be “electrically long.” To test this idea, we consider a model in which a neurite is treated as a long, narrow body, and it is subjected to a stimulus created by electrodes situated in the region external to it. With regard to this electric stimulus, the neurite can be treated as a passive cable. Assuming adequate symmetry so that the tissue packed with multiple cables is equivalent to an isolated system consisting of a single cable and a surrounding extracellular resistive medium, we analytically calculate the extracellular potential of the tissue in response to such an externally created alternating-current electric field using a Green's function that we obtained previously. Our results show that brain tissue modeled by such a cable existing within a purely resistive extracellular medium exhibits a large effective permittivity in the low-frequency region. Moreover, we obtain results suggesting that an extremely large low-frequency permittivity can coexist with weak low-pass filter characteristics in brain tissue.

  19. Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery.

    Science.gov (United States)

    Blumcke, Ingmar; Spreafico, Roberto; Haaker, Gerrit; Coras, Roland; Kobow, Katja; Bien, Christian G; Pfäfflin, Margarete; Elger, Christian; Widman, Guido; Schramm, Johannes; Becker, Albert; Braun, Kees P; Leijten, Frans; Baayen, Johannes C; Aronica, Eleonora; Chassoux, Francine; Hamer, Hajo; Stefan, Hermann; Rössler, Karl; Thom, Maria; Walker, Matthew C; Sisodiya, Sanjay M; Duncan, John S; McEvoy, Andrew W; Pieper, Tom; Holthausen, Hans; Kudernatsch, Manfred; Meencke, H Joachim; Kahane, Philippe; Schulze-Bonhage, Andreas; Zentner, Josef; Heiland, Dieter H; Urbach, Horst; Steinhoff, Bernhard J; Bast, Thomas; Tassi, Laura; Lo Russo, Giorgio; Özkara, Cigdem; Oz, Buge; Krsek, Pavel; Vogelgesang, Silke; Runge, Uwe; Lerche, Holger; Weber, Yvonne; Honavar, Mrinalini; Pimentel, José; Arzimanoglou, Alexis; Ulate-Campos, Adriana; Noachtar, Soheyl; Hartl, Elisabeth; Schijns, Olaf; Guerrini, Renzo; Barba, Carmen; Jacques, Thomas S; Cross, J Helen; Feucht, Martha; Mühlebner, Angelika; Grunwald, Thomas; Trinka, Eugen; Winkler, Peter A; Gil-Nagel, Antonio; Toledano Delgado, Rafael; Mayer, Thomas; Lutz, Martin; Zountsas, Basilios; Garganis, Kyriakos; Rosenow, Felix; Hermsen, Anke; von Oertzen, Tim J; Diepgen, Thomas L; Avanzini, Giuliano

    2017-10-26

    Detailed neuropathological information on the structural brain lesions underlying seizures is valuable for understanding drug-resistant focal epilepsy. We report the diagnoses made on the basis of resected brain specimens from 9523 patients who underwent epilepsy surgery for drug-resistant seizures in 36 centers from 12 European countries over 25 years. Histopathological diagnoses were determined through examination of the specimens in local hospitals (41%) or at the German Neuropathology Reference Center for Epilepsy Surgery (59%). The onset of seizures occurred before 18 years of age in 75.9% of patients overall, and 72.5% of the patients underwent surgery as adults. The mean duration of epilepsy before surgical resection was 20.1 years among adults and 5.3 years among children. The temporal lobe was involved in 71.9% of operations. There were 36 histopathological diagnoses in seven major disease categories. The most common categories were hippocampal sclerosis, found in 36.4% of the patients (88.7% of cases were in adults), tumors (mainly ganglioglioma) in 23.6%, and malformations of cortical development in 19.8% (focal cortical dysplasia was the most common type, 52.7% of cases of which were in children). No histopathological diagnosis could be established for 7.7% of the patients. In patients with drug-resistant focal epilepsy requiring surgery, hippocampal sclerosis was the most common histopathological diagnosis among adults, and focal cortical dysplasia was the most common diagnosis among children. Tumors were the second most common lesion in both groups. (Funded by the European Union and others.).

  20. Long-Term Tissue Culture of Adult Brain and Spleen Slices on Nanostructured Scaffolds.

    Science.gov (United States)

    Kallendrusch, Sonja; Merz, Felicitas; Bechmann, Ingo; Mayr, Stefan G; Zink, Mareike

    2017-05-01

    Long-term tissue culture of adult mammalian organs is a highly promising approach to bridge the gap between single cell cultures and animal experiments, and bears the potential to reduce in vivo studies. Novel biomimetic materials open up new possibilities to maintain the complex tissue structure in vitro; however, survival times of adult tissues ex vivo are still limited to a few days with established state-of-the-art techniques. Here, it is demonstrated that TiO2 nanotube scaffolds with specific tissue-tailored characteristics can serve as superior substrates for long-term adult brain and spleen tissue culture. High viability of the explants for at least two weeks is achieved and compared to tissues cultured on standard polytetrafluoroethylene (PTFE) membranes. Histological and immunohistochemical staining and live imaging are used to investigate tissue condition after 5 and 14 d in vitro, while environmental scanning electron microscopy qualifies the interaction with the underlying scaffold. In contrast to tissues cultured on PTFE membranes, enhanced tissue morphology is detected in spleen slices, as well as minor cell death in neuronal tissue, both cultured on nanotube scaffolds. This novel biomimetic tissue model will prove to be useful to address fundamental biological and medical questions from tissue regeneration up to tumor progression and therapeutic approaches. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Integrin suppresses neurogenesis and regulates brain tissue assembly in planarian regeneration.

    Science.gov (United States)

    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.

  2. The Neuroprotective Effect of Cornus mas on Brain Tissue of Wistar Rats

    Directory of Open Access Journals (Sweden)

    Renata Francik

    2014-01-01

    Full Text Available Cornelian cherry (Cornus mas is a valuable source of phenolic antioxidants. Flavonoid derivatives as nonenzymatic antioxidants are important in the pathophysiology of many diseases including neurological disorders (e.g., Alzheimer’s disease or heart disease. In this study, we examined the effect of an addition of freeze-dried fruit of cornelian cherry on three types of diets: control diet, fructose diet, and diet enriched in fats (high-fat diet. This effect was studied by determining the following antioxidant parameters in both brain tissue and plasma in rats: catalase, ferric reducing ability of plasma, paraoxonase, protein carbonyl groups, and free thiol groups. Results indicate that both fructose diet and high-fat diet affect the antioxidant capacity of the organism. Furthermore, an addition of cornelian cherry resulted in increased activity of catalase in brain tissue, while in plasma it caused the opposite effect. In turn, with regard to paraoxonase activity in both brain tissue and plasma, it had a stimulating effect. Adding cornelian cherry to the tested diets increased the activity of PON in both tested tissues. Moreover, protective effect of fruits of this plant was observed in the process of oxidation of proteins by decreasing levels of protein carbonyl groups and thiol groups in brain tissue as well as in plasma.

  3. Mice Brain Tissue Injury Induced by Diisononyl Phthalate Exposure and the Protective Application of Vitamin E.

    Science.gov (United States)

    Peng, Ling

    2015-07-01

    As a widely used plasticizer in plastic industry, the data of diisononyl phthalate (DINP) toxicity due to exposure are insufficient. This work investigated the brain tissue injury induced by DINP exposure. Through oral exposure to DINP, oxidative stress, inflammatory responses, apoptosis, and hippocampus pathological alterations were found in the mice brain. And through the Morris water maze test, cognitive deficits were tested. Our data also showed that these exacerbations were counteracted by vitamin E. These results above indicated that oral exposure of mice to DINP induced brain damage, and oxidative stress, inflammation, and the consequential apoptosis jointly constituted the potential mechanisms of such induced toxicity. © 2015 Wiley Periodicals, Inc.

  4. Modeling invasion of brain tissue by glioblastoma cells: ECM alignment and motility

    Science.gov (United States)

    Sander, L. M.

    2013-03-01

    A key stage in the development of highly malignant brain tumors (Glioblastoma Multiforme) is invasion of normal brain tissue by motile cells moving through a crowded, complex environment. Evidence from in vitro experiments suggests the cell motion is accompanied by considerable deformation and alignment of the extra-cellular matrix (ECM) of the brain. In the case of breast cancer, alignment effects of this sort have been seen in vivo. We have modeled features of this system including stress confinement in the non-linear elasticity of the ECM and contact guidance of the cell motion.

  5. Transplantation of three-dimensional artificial human vascular tissues fabricated using an extracellular matrix nanofilm-based cell-accumulation technique.

    Science.gov (United States)

    Asano, Yoshiya; Shimoda, Hiroshi; Okano, Daisuke; Matsusaki, Michiya; Akashi, Mitsuru

    2017-04-01

    We have established a novel three-dimensional (3D) tissue-constructing technique, referred to as the 'cell-accumulation method', which is based on the self-assembly of cultured human cells. In this technique, cells are coated with fibronectin and gelatin to construct extracellular matrix (ECM) nanofilms and cultured to form multi-layers in vitro. By using this method, we have successfully fabricated artificial tissues with vascular networks constructed by co-cultivation of human umbilical vein-derived vascular endothelial cells between multi-layers of normal human dermal fibroblasts. In this study, to assess these engineered vascular tissues as therapeutic implants, we transplanted the 3D human tissues with microvascular networks, fabricated based on the cell-accumulation method, onto the back skin of nude mice. After the transplantation, we found vascular networks with perfusion of blood in the transplanted graft. At the boundary between host and implanted tissue, connectivity between murine and human vessels was found. Transmission electron microscopy of the implanted artificial vascular tubules demonstrated the ultrastructural features of blood capillaries. Moreover, maturation of the vascular tissues after transplantation was shown by the presence of pericyte-like cells and abundant collagen fibrils in the ECM surrounding the vasculature. These results demonstrated that artificial human vascular tissues constructed by our method were engrafted and matured in animal skin. In addition, the implanted artificial human vascular networks were connected with the host circulatory system by anastomosis. This method is an attractive technique for engineering prevascularized artificial tissues for transplantation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Effects of tissue fixation on coherent anti-Stokes Raman scattering images of brain

    Science.gov (United States)

    Galli, Roberta; Uckermann, Ortrud; Koch, Edmund; Schackert, Gabriele; Kirsch, Matthias; Steiner, Gerald

    2014-07-01

    Coherent anti-Stokes Raman scattering (CARS) microscopy is an emerging multiphoton technique for the label-free histopathology of the central nervous system, by imaging the lipid content within the tissue. In order to apply the technique on standard histology sections, it is important to know the effects of tissue fixation on the CARS image. Here, we report the effects of two common fixation methods, namely with formalin and methanol-acetone, on mouse brain and human glioblastoma tissue. The variations induced by fixation on the CARS contrast and intensity were compared and interpreted using Raman microspectroscopy. The results show that, whenever unfixed cryosections cannot be used, fixation with formalin constitutes an alternative which does not deteriorate substantially the contrast generated by the different brain structures in the CARS image. Fixation with methanol-acetone strongly modifies the tissue lipid content and is therefore incompatible with the CARS imaging.

  7. Brain Tissue Compartment Density Estimated Using Diffusion-Weighted MRI Yields Tissue Parameters Consistent With Histology

    OpenAIRE

    Sepehrband, Farshid; Clark, Kristi A.; Ullmann, Jeremy F. P.; Kurniawan, Nyoman D; Leanage, Gayeshika; Reutens, David C.; Yang, Zhengyi

    2015-01-01

    We examined whether quantitative density measures of cerebral tissue consistent with histology can be obtained from diffusion magnetic resonance imaging (MRI). By incorporating prior knowledge of myelin and cell membrane densities, absolute tissue density values were estimated from relative intra-cellular and intra-neurite density values obtained from diffusion MRI. The NODDI (neurite orientation distribution and density imaging) technique, which can be applied clinically, was used. Myelin de...

  8. Changes in brain tissue and behavior patterns induced by single short-term fasting in mice.

    Science.gov (United States)

    Hisatomi, Yuko; Asakura, Kyo; Kugino, Kenji; Kurokawa, Mamoru; Asakura, Tomiko; Nakata, Keiko

    2013-01-01

    In humans, emaciation from long-term dietary deficiencies, such as anorexia, reportedly increases physical activity and brain atrophy. However, the effects of single short-term fasting on brain tissue or behavioral activity patterns remain unclear. To clarify the impact of malnutrition on brain function, we conducted a single short-term fasting study as an anorexia model using male adult mice and determined if changes occurred in migratory behavior as an expression of brain function and in brain tissue structure. Sixteen-week-old C57BL/6J male mice were divided into either the fasted group or the control group. Experiments were conducted in a fixed indoor environment. We examined the effects of fasting on the number of nerve cells, structural changes in the myelin and axon density, and brain atrophy. For behavior observation, the amount of food and water consumed, ingestion time, and the pattern of movement were measured using a time-recording system. The fasted mice showed a significant increase in physical activity and their rhythm of movement was disturbed. Since the brain was in an abnormal state after fasting, mice that were normally active during the night became active regardless of day or night and performed strenuous exercise at a high frequency. The brain weight did not change by a fast, and brain atrophy was not observed. Although no textural change was apparent by fasting, the neuronal neogenesis in the subventricular zone and hippocampus was inhibited, causing disorder of the brain function. A clear association between the suppression of encephalic neuropoiesis and overactivity was not established. However, it is interesting that the results of this study suggest that single short-term fasting has an effect on encephalic neuropoiesis.

  9. Expression of lymphocyte coding genes in peripheral blood and lymphocyte infiltration in cardiac tissues influenced by cyclosporin A in heterotopic heart transplantation model in rats.

    Science.gov (United States)

    Xu, Xiu-fang; Xin, Yi; Zhang, Ying; Huang, Yi-min; Li, Wen-bin; Li, Na; Lin, Zheng; Zhou, Yu-jie; Zhang, Zhao-guang

    2013-12-01

    To systematically compare the expression of coding genes with pathological changes of transplanted cardiac tissue and peripheral blood lymphocytes in an allo-heterotopic rat cardiac transplant model. Using SD rats as donors and Wistar rats as recipients, animals were divided into two groups, control and cyclosporine A intervention plus heart transplant groups. After transplant at 1, 3, 7, 10 and 12d, we assessed the ability of lymphocytes to infiltrate into cardiac tissues and levels of leukocyte coding genes in peripheral blood. Histopathological changes were monitored in cardiac tissue to determine the level of transplant rejection. (1) 24h after transplant peripheral blood lymphocytes' transcription and expression were temporarily reduced. (2) CD4(+) and CD8(+) lymphocytes infiltrate into cardiac tissue and Grade 1R pathological changes were observed 3d-7d after heart transplant. (3)Cyclosporine A was not able to completely block heart transplant rejection.(4) Although cyclosporine A was not able to effectively suppress CD4(+) T cell gene expression, it did suppress CD8(+) T cell gene transcription. (5) Cyclosporine A did not effectively reduce the rapid infiltration of CD4(+) or CD8(+) infiltration in 3d, but significantly reduced the degree of CD4(+) T cell infiltration in cardiac tissues between 3 and 7d. (6) Differential display (DD-PCR): Graft control group: there were differences in 2,3-bisphosphoglycerate, ribosomal protein S25, 12S ribosomal, gig18, MHC-III and ATPase H(+), which occurred 24h before CD4/CD8 surface protein expression. Cyclosporine A group: there were differences in thrombospondin-1, TCR, 2,3-bisphosphoglycerate, sodium channel beta-1, gig18 and TCR. In the cyclosporine A group 2,3-bisphosphoglycerate positive expression was observed 24h after the control group, which indicates that cyclosporine A slowed down the 2,3-bisphosphoglycerate transcription rate in peripheral lymphocytes and delayed its expression time. Cyclosporine A also

  10. Analysis of sports related mTBI injuries caused by elastic wave propagation through brain tissue

    OpenAIRE

    Case, D.; Richer, E.

    2016-01-01

    Repetitive concussions and sub-concussions suffered by athletes have been linked to a series of sequelae ranging from traumatic encephalopathy to dementia pugilistica. A detailed finite element model of the human head was developed based on standard libraries of medical imaging. The model includes realistic material properties for the brain tissue, bone, soft tissue, and CSF, as well as the structure and properties of a protective helmet. Various impact scenarios were studied, with a focus on...

  11. Gene expression changes with age in skin, adipose tissue, blood and brain.

    Science.gov (United States)

    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.

  12. Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland

    DEFF Research Database (Denmark)

    Dewailly, Éric; Mulvad, Gert; Pedersen, Henning S.

    1999-01-01

    report results of organochlorine determination in liver, brain, omental fat, and subcutaneous abdominal fat samples collected from deceased Greenlanders between 1992 and 1994. Eleven chlorinated pesticides and 14 polychlorinated biphenyl congeners were measured in tissue lipid extracts by high......-resolution gas chromatography with electron capture detection. Mean concentrations of polychlorinated biphenyls, 2, 2'-bis(4-chlorophenyl)-1,1-dichloroethylene, ss-hexachlorocyclohexane, hexachlorobenzene, mirex, trans-nonachlor, and oxychlordane in adipose tissue samples from Greenlanders were 3-34-fold higher...

  13. Apparatus dependence of normal brain tissue dose in stereotactic radiosurgery for multiple brain metastases.

    Science.gov (United States)

    Ma, Lijun; Petti, Paula; Wang, Brian; Descovich, Martina; Chuang, Cynthia; Barani, Igor J; Kunwar, Sandeep; Shrieve, Dennis C; Sahgal, Arjun; Larson, David A

    2011-06-01

    Technical improvements in commercially available radiosurgery platforms have made it practical to treat a large number of intracranial targets. The goal of this study was to investigate whether the dose to normal brain when planning radiosurgery to multiple targets is apparatus dependent. The authors selected a single case involving a patient with 12 metastatic lesions widely distributed throughout the brain as visualized on contrast-enhanced CT. Target volumes and critical normal structures were delineated with Leksell Gamma Knife Perfexion software. The imaging studies including the delineated contours were digitally exported into the CyberKnife and Novalis multileaf collimator-based planning systems for treatment planning using identical target dose goals and dose-volume constraints. Subsets of target combinations (3, 6, 9, or 12 targets) were planned separately to investigate the relationship of number of targets and radiosurgery platform to the dose to normal brain. Despite similar target dose coverage and dose to normal structures, the dose to normal brain was strongly apparatus dependent. A nonlinear increase in dose to normal brain volumes with increasing number of targets was also noted. The dose delivered to normal brain is strongly dependent on the radiosurgery platform. How general this conclusion is and whether apparatus-dependent differences are related to differences in hardware design or differences in dose-planning algorithms deserve further investigation.

  14. Morte encefálica, cuidados ao doador de órgãos e transplante de pulmão Brain death, multiorgan donor and lung transplantation

    Directory of Open Access Journals (Sweden)

    Fernando D'Império

    2007-03-01

    patients. This position is a result of great advances in the field of immunology, critical care medicine and pharmacology. However, organ transplantation is now suffering from its own success as the number of patients in waiting lists is dramatically increasing the same is not happening with organ availability results in increasing number of mortalities while waiting for transplantation. Transplant community responses to this situation consist of reviewing the criteria for organ acceptability and developing new strategies to get organs as the called non-heart beating organ donors. CONTENTS: However the physiopathology of brain death and its consequences are now better understood helping in such patients' management. The purpose of this review is to help to identify the most important clinical and therapeutic aspects related to its physiopathology as depletion of vasoactives substances and its importance in the management of cardio and respiratory systems. We also discuss endocrine and hidroelectrolytes disturbances. Organ specific data are also focused in order to offer a whole view of donor management. CONCLUSIONS: It is important to observe that new technologies will be available in the near future to diminish the low rate between organ availability and organ waiting patients. In conclusion, with the raising numbers in transplant waiting lists and scarce resources of organs make us believe that we have to improve the management of multi organ donors and the preservation technology in order to reduce the mortality in such waiting lists.

  15. Study into penetration speed during laser cutting of brain tissues.

    Science.gov (United States)

    Yilbas, Z; Sami, M; Patiroglu, T

    1998-01-01

    The applications of CO2 continuous-wave lasers in neurosurgery have become important in recent years. Theoretical considerations of laser applicability in medicine are subsequently confirmed experimentally. To obtain precision operation in the laser cutting process, further theoretical developments and experimental studies need to be conducted. Consequently, in the present study, the heat transfer mechanism taking place during laser-tissue interaction is introduced using Fourier theory. The results obtained from the theoretical model are compared with the experimental results. In connection with this, an experiment is designed to measure the penetration speed during the laser cutting process. The measurement is carried out using an optical method. It is found that both results for the penetration speed obtained from the theory and experiment are in a good agreement.

  16. Brain tissue segmentation using q-entropy in multiple sclerosis magnetic resonance images

    Energy Technology Data Exchange (ETDEWEB)

    Diniz, P.R.B.; Brum, D.G. [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Medicina. Dept. de Neurociencias e Ciencias do Comportamento; Santos, A. C. [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Medicina. Dept. de Clinica Medica; Murta-Junior, L.O.; Araujo, D.B. de, E-mail: murta@usp.b [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Faculdade de Filosofia, Ciencias e Letras. Dept. de Fisica e Matematica

    2010-01-15

    The loss of brain volume has been used as a marker of tissue destruction and can be used as an index of the progression of neurodegenerative diseases, such as multiple sclerosis. In the present study, we tested a new method for tissue segmentation based on pixel intensity threshold using generalized Tsallis entropy to determine a statistical segmentation parameter for each single class of brain tissue. We compared the performance of this method using a range of different q parameters and found a different optimal q parameter for white matter, gray matter, and cerebrospinal fluid. Our results support the conclusion that the differences in structural correlations and scale invariant similarities present in each tissue class can be accessed by generalized Tsallis entropy, obtaining the intensity limits for these tissue class separations. In order to test this method, we used it for analysis of brain magnetic resonance images of 43 patients and 10 healthy controls matched for gender and age. The values found for the entropic q index were 0.2 for cerebrospinal fluid, 0.1 for white matter and 1.5 for gray matter. With this algorithm, we could detect an annual loss of 0.98% for the patients, in agreement with literature data. Thus, we can conclude that the entropy of Tsallis adds advantages to the process of automatic target segmentation of tissue classes, which had not been demonstrated previously. (author)

  17. Bimodal Spectroscopy of Formalin Fixed Samples to Discriminate Dysplastic and Tumor Brain Tissues

    Directory of Open Access Journals (Sweden)

    Anand S.

    2014-12-01

    Full Text Available Biomedical spectroscopy has gained attention in the past few years for disease diagnosis. Fluorescence and Raman spectroscopies provide finger-print information related to biochemical and morphological alterations when tissues progress from the normal to a malignant stage. Usually, freshly excised tissue specimens are preferred for bio-spectroscopic studies. However, ethical issues, sample availability and distance between the surgery room and the laboratory provide an impelling restriction for in-vitro spectroscopic studies using freshly excised samples. After surgical resection tissues are fixed in 4% formalin for histological studies under a light microscope. The process of fixation prevents degradation of tissues. In this study, we probe the use of formalin fixed sample for differentiating normal and dysplastic brain tissues using fluorescence and Raman spectroscopies. It was found that fluorescence spectral profile changes in the wavelength range from 550-750 nm between dysplastic and tumor samples. Also, significant differences were found in the Raman spectral profiles of such samples. The results indicate a potential diagnostic application of spectroscopy in formalin fixed brain samples for differentiating dysplastic and tumor brain tissues.

  18. Brain tissue segmentation using q-entropy in multiple sclerosis magnetic resonance images

    Directory of Open Access Journals (Sweden)

    P.R.B. Diniz

    2010-01-01

    Full Text Available The loss of brain volume has been used as a marker of tissue destruction and can be used as an index of the progression of neurodegenerative diseases, such as multiple sclerosis. In the present study, we tested a new method for tissue segmentation based on pixel intensity threshold using generalized Tsallis entropy to determine a statistical segmentation parameter for each single class of brain tissue. We compared the performance of this method using a range of different q parameters and found a different optimal q parameter for white matter, gray matter, and cerebrospinal fluid. Our results support the conclusion that the differences in structural correlations and scale invariant similarities present in each tissue class can be accessed by generalized Tsallis entropy, obtaining the intensity limits for these tissue class separations. In order to test this method, we used it for analysis of brain magnetic resonance images of 43 patients and 10 healthy controls matched for gender and age. The values found for the entropic q index were 0.2 for cerebrospinal fluid, 0.1 for white matter and 1.5 for gray matter. With this algorithm, we could detect an annual loss of 0.98% for the patients, in agreement with literature data. Thus, we can conclude that the entropy of Tsallis adds advantages to the process of automatic target segmentation of tissue classes, which had not been demonstrated previously.

  19. Differential expression of the bone and the liver tissue non-specific alkaline phosphatase isoforms in brain tissues.

    Science.gov (United States)

    Brun-Heath, Isabelle; Ermonval, Myriam; Chabrol, Elodie; Xiao, Jinsong; Palkovits, Miklós; Lyck, Ruth; Miller, Florence; Couraud, Pierre-Olivier; Mornet, Etienne; Fonta, Caroline

    2011-03-01

    The enzyme tissue non-specific alkaline phosphatase (TNAP) belongs to the ectophosphatase family. It is present in large amounts in bone in which it plays a role in mineralization but little is known about its function in other tissues. Arguments are accumulating for its involvement in the brain, in particular in view of the neurological symptoms accompanying human TNAP deficiencies. We have previously shown, by histochemistry, alkaline phosphatase (AP) activity in monkey brain vessels and parenchyma in which AP exhibits specific patterns. Here, we clearly attribute this activity to TNAP expression rather than to other APs in primates (human and marmoset) and in rodents (rat and mouse). We have not found any brain-specific transcripts but our data demonstrate that neuronal and endothelial cells exclusively express the bone TNAP transcript in all species tested, except in mouse neurons in which liver TNAP transcripts have also been detected. Moreover, we highlight the developmental regulation of TNAP expression; this also acts during neuronal differentiation. Our study should help to characterize the regulation of the expression of this ectophosphatase in various cell types of the central nervous system.

  20. Avaliação da Barreira Hemato-Encefálica no transplante de medula óssea Blood-Brain Barrier evaluation in bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    1997-01-01

    Full Text Available A barreira hemato-encefálica (BHE contribui para o isolamento imunológico do sistema nervoso central (SNC. Sua avaliação nunca foi realizada em pacientes submetidos a transplante de medula óssea (TMO. Neste estudo a integridade da BHE foi avaliada através das proteínas do LCR, de forma quantitativa, a fim de observar a incidência e entender a fisiopatologia da doença do enxerto contra o hospedeiro crônica (DECH-C no SNC. Foram estudadas amostras pareadas de LCR e soro de 33 pacientes com leucemia mielóide crônica submetidos a TMO alogênico, de doador aparentado, HLA idêntico. As amostras foram coletadas nos períodos pré TMO, pós TMO e concomitante à DECH-C. Não foi evidenciada quebra de BHE durante a DECH-C em nenhum dos casos estudados.The blood-brain barrier (BBB contributes to the central nervous system (CNS immunological isolation. BBB has never been studied in patients who developed chronic graft-versus-host disease (GVHD after allogeneic bone marrow transplants (BMT, from HLA identical related donors. BBB disruption was investigated through the cerebrospinal fluid (CSF proteins, quantitative and graphically, in order to detect the incidence and possible pathophysiology of the CNS involvement in chronic GVHD. Thirty three CSF and matched serum samples from chronic myeloid leukemia patients were collected pre BMT, pos BMT and during chronic GVHD. There was no evidence of BBB disruption in any patient studied.

  1. Is human blood a good surrogate for brain tissue in transcriptional studies?

    Directory of Open Access Journals (Sweden)

    van den Berg Leonard H

    2010-10-01

    Full Text Available Abstract Background Since human brain tissue is often unavailable for transcriptional profiling studies, blood expression data is frequently used as a substitute. The underlying hypothesis in such studies is that genes expressed in brain tissue leave a transcriptional footprint in blood. We tested this hypothesis by relating three human brain expression data sets (from cortex, cerebellum and caudate nucleus to two large human blood expression data sets (comprised of 1463 individuals. Results We found mean expression levels were weakly correlated between the brain and blood data (r range: [0.24,0.32]. Further, we tested whether co-expression relationships were preserved between the three brain regions and blood. Only a handful of brain co-expression modules showed strong evidence of preservation and these modules could be combined into a single large blood module. We also identified highly connected intramodular "hub" genes inside preserved modules. These preserved intramodular hub genes had the following properties: first, their expression levels tended to be significantly more heritable than those from non-preserved intramodular hub genes (p -90; second, they had highly significant positive correlations with the following cluster of differentiation genes: CD58, CD47, CD48, CD53 and CD164; third, a significant number of them were known to be involved in infection mechanisms, post-transcriptional and post-translational modification and other basic processes. Conclusions Overall, we find transcriptome organization is poorly preserved between brain and blood. However, the subset of preserved co-expression relationships characterized here may aid future efforts to identify blood biomarkers for neurological and neuropsychiatric diseases when brain tissue samples are unavailable.

  2. Tissue sparing, behavioral recovery, supraspinal axonal sparing/regeneration following sub-acute glial transplantation in a model of spinal cord contusion

    Science.gov (United States)

    2013-01-01

    Background It has been shown that olfactory ensheathing glia (OEG) and Schwann cell (SCs) transplantation are beneficial as cellular treatments for spinal cord injury (SCI), especially acute and sub-acute time points. In this study, we transplanted DsRED transduced adult OEG and SCs sub-acutely (14 days) following a T10 moderate spinal cord contusion injury in the rat. Behaviour was measured by open field (BBB) and horizontal ladder walking tests to ascertain improvements in locomotor function. Fluorogold staining was injected into the distal spinal cord to determine the extent of supraspinal and propriospinal axonal sparing/regeneration at 4 months post injection time point. The purpose of this study was to investigate if OEG and SCs cells injected sub acutely (14 days after injury) could: (i) improve behavioral outcomes, (ii) induce sparing/regeneration of propriospinal and supraspinal projections, and (iii) reduce tissue loss. Results OEG and SCs transplanted rats showed significant increased locomotion when compared to control injury only in the open field tests (BBB). However, the ladder walk test did not show statistically significant differences between treatment and control groups. Fluorogold retrograde tracing showed a statistically significant increase in the number of supraspinal nuclei projecting into the distal spinal cord in both OEG and SCs transplanted rats. These included the raphe, reticular and vestibular systems. Further pairwise multiple comparison tests also showed a statistically significant increase in raphe projecting neurons in OEG transplanted rats when compared to SCs transplanted animals. Immunohistochemistry of spinal cord sections short term (2 weeks) and long term (4 months) showed differences in host glial activity, migration and proteoglycan deposits between the two cell types. Histochemical staining revealed that the volume of tissue remaining at the lesion site had increased in all OEG and SCs treated groups. Significant

  3. [Transplant coordination and logistics of intra and extra-hospital cadaver donor tissue. "The Pamplona Model". Sequence of tasks performed from 1992-2006].

    Science.gov (United States)

    Maraví-Poma, E; Martín, A; Maraví-Aznar, A; Iturralde, O; Compains, E; Alvarez, J; Cabal, S; Maraví-Aznar, E; Teijeira, R; Unzué, Jj; González, R

    2006-01-01

    Tissue and organ donations are the only option for many patients. Cerebral death (CD) facilitates this approach. However, hospitals that do not provide CD donors have to adapt in order to obtain donors, referred to as tissue donors (TD), who have died from cardiac arrest. Is this paper it descripte the model for coordination and donation of intra and extra-hospital TD in the Autonomous Community of Navarra. It creats a program for detection, donation and extractions called the Pamplona Model, from 1992-2006. In 1990, a transplant team was created by an Intensive Medicine Physician of HVC, INML and SOS-Navarra. In 1996, VCH Transplant Coordination is defined as a reference centre for the Tissue Transplant Programme in the Autonomous Community of Navarra. Consensus protocols for "intra and extra-hospital detection" of persons having died from cardiac arrest are developed: - Alerts from NHS-O hospitals, SOS-Navarra; judges and INML forensic pathologists. - Criteria for selection, search and contacts with relatives. - Alert serology, extraction and transport teams. - Logistics and distribution of tissue. - Agreed incentives: Economic, administrative and relevant regulations. The Pamplona Model, with the Virgen Del Camino hospital has made important contributions and is unique in the world. Intra and extra-hospital coordination of cadaver donor from a referred hospital, it is a scientific and organizational advance to have in it counts for the creation of extraction and transplant tissues teams.

  4. Transplantation of human fetal tissue for neurodegenerative diseases: validation of a new protocol for microbiological analysis and bacterial decontamination.

    Science.gov (United States)

    Piroth, Tobias; Pauly, Marie-Christin; Schneider, Christian; Wittmer, Annette; Möllers, Sven; Döbrössy, Máté; Winkler, Christian; Nikkhah, Guido

    2014-01-01

    Restorative cell therapy concepts in neurodegenerative diseases are aimed at replacing lost neurons. Despite advances in research on pluripotent stem cells, fetal tissue from routine elective abortions is still regarded as the only safe cell source. Progenitor cells isolated from distinct first-trimester fetal CNS regions have already been used in clinical trials and will be used again in a new multicenter trial funded by the European Union (TRANSEURO). Bacterial contamination of human fetal tissue poses a potential risk of causing infections in the brain of the recipient. Thus, effective methods of microbial decontamination and validation of these methods are required prior to approval of a neurorestorative cell therapy trial. We have developed a protocol consisting of subsequent washing steps at different stages of tissue processing. Efficacy of microbial decontamination was assessed on rat embryonic tissue incubated with high concentrations of defined microbe solutions including representative bacterial and fungal species. Experimental microbial contamination was reduced by several log ranks. Subsequently, we have analyzed the spectrum of microbial contamination and the effect of subsequent washing steps on aborted human fetal tissue; 47.7% of the samples taken during human fetal tissue processing were positive for a microbial contamination, but after washing, no sample exhibited bacterial growth. Our data suggest that human fetal tissue for neural repair can carry microbes of various species, highlighting the need for decontamination procedures. The decontamination protocol described in this report has been shown to be effective as no microbes could be detected at the end of the procedure.

  5. Laser method of biological activity stimulation of cryoconserved hemopoietic tissue transplant

    Science.gov (United States)

    Khyznyak, Anatoly I.; Lesnik, Svetlana A.; Kogut, Georgy I.; Glukhenkaya, Galina T.

    1994-02-01

    The biological activity of cryoconserved fetal liver cells of mice (FLM) having undergone the He-Ne laser action has been estimated by the efficiency of their transplantation to mice- recipients exposed to lethal x-ray dose. The survival rate 30 days after x-ray exposure for those mice was 75% in comparison with 70% for mice with cryoconserved nonirradiated graft. The trial animals' peripheral blood investigations have been made. The obtained results indicate that the laser method of cryoconserved cells stimulation can help to increase the therapeutic efficiency of mielotransplantation.

  6. Atlas-based segmentation of developing tissues in the human brain with quantitative validation in young fetuses.

    Science.gov (United States)

    Habas, Piotr A; Kim, Kio; Rousseau, Francois; Glenn, Orit A; Barkovich, A James; Studholme, Colin

    2010-09-01

    Imaging of the human fetus using magnetic resonance (MR) is an essential tool for quantitative studies of normal as well as abnormal brain development in utero. However, because of fundamental differences in tissue types, tissue properties and tissue distribution between the fetal and adult brain, automated tissue segmentation techniques developed for adult brain anatomy are unsuitable for this data. In this paper, we describe methodology for automatic atlas-based segmentation of individual tissue types in motion-corrected 3D volumes reconstructed from clinical MR scans of the fetal brain. To generate anatomically correct automatic segmentations, we create a set of accurate manual delineations and build an in utero 3D statistical atlas of tissue distribution incorporating developing gray and white matter as well as transient tissue types such as the germinal matrix. The probabilistic atlas is associated with an unbiased average shape and intensity template for registration of new subject images to the space of the atlas. Quantitative whole brain 3D validation of tissue labeling performed on a set of 14 fetal MR scans (20.57-22.86 weeks gestational age) demonstrates that this atlas-based EM segmentation approach achieves consistently high DSC performance for the main tissue types in the fetal brain. This work indicates that reliable measures of brain development can be automatically derived from clinical MR imaging and opens up possibility of further 3D volumetric and morphometric studies with multiple fetal subjects. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc.

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

    Science.gov (United States)

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

    2011-02-01

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

  8. Transmission routes of HIV-1 gp120 from brain to lymphoid tissues.

    Science.gov (United States)

    Cashion, M F; Banks, W A; Bost, K L; Kastin, A J

    1999-03-20

    The blood-brain barrier (BBB) restricts the entry of antiviral agents into the CNS thereby facilitating the creation of a reservoir of HIV that could potentially reinfect peripheral tissues. We characterized the efflux from brain of radioactively labeled viral coat HIV-1 gp120 (I-gp120) after intracerebroventricular (i.c.v.) injection. The half-time disappearance rate of I-gp120 from brain was 12.6 min, which was faster than could be explained by the reabsorption of cerebrospinal fluid into blood but could not be explained by a saturable transporter. After i.c.v. injection, I-gp120 appeared in the serum and was sequestered by spleen and the cervical nodes, demonstrating a potential for virus within the CNS to reinfect peripheral tissues. However, the amount of I-gp120 appearing in serum was less than that expected based on the efflux rate, whereas uptake by the cervical nodes was much greater after i. c.v. than after i.v. injection of I-gp120. These findings were explained by drainage from the brain directly to the cervical lymph nodes through the brain's primitive lymphatic system. These lymphatics potentially provide a pathway through which CNS reservoirs of HIV-1 could directly reinfect lymphoid tissue without being exposed to circulating antiviral agents. Copyright 1999 Elsevier Science B.V.

  9. Elderly depression diagnostic of diabetic patients by brain tissue pulsatility imaging

    Science.gov (United States)

    Hachemi, Mélouka Elkateb; Remeniéras, Jean-pierre; Desmidt, Thomas; Camus, Vincent; Tranquart, François

    2010-01-01

    Pulsatile motion of brain parenchyma results from cardiac and breathing cycles and consists in a rapid displacement in systole, with slow diastolic recovery. Based on the vascular depression concept and recent studies where a correlation was found between cerebral haemodynamics and depression in the elderly, we emitted the hypothesis that tissue brain motion due to perfusion is correlated to elderly depression associated with cardiovascular risk factors. Tissue Pulsatlity Imaging (TPI) is a new ultrasound technique developed firstly at the University of Washington to assess the brain tissue motion. We used TPI technique to measure the brain displacement of two groups of elderly patients with diabetes as a vascular risk factor. The first group is composed of 11 depressed diabetic patients. The second group is composed of 12 diabetic patients without depressive symptoms. Transcranial acquisitions were performed with a 1.8 MHz ultrasound phased array probe through the right temporal bone window. The acquisition of six cardiac cycles was realized on each patient with a frame rate of 23 frames/s. Displacements estimation was performed by off-line analysis. A significant decrease in brain pulsatility was observed in the group of depressed patients compared to the group of non depressed patients. Mean displacement magnitude was about 44±7 μm in the first group and 68±13 μm in the second group.

  10. Restricted spontaneous in vitro differentiation and region-specific migration of long-term expanded fetal human neural precursor cells after transplantation into the adult rat brain.

    Science.gov (United States)

    Maciaczyk, Jaroslaw; Singec, Ilyas; Maciaczyk, Donata; Klein, Alexander; Nikkhah, Guido

    2009-09-01

    Human fetal neural stem/progenitor cells (hNSCs) are investigated for their potential as a cell source for cell-based therapies in neurodegenerative diseases. However, the limited availability of fetal tissue and insufficient understanding of the lineage-dependent pattern of survival, migration, and differentiation following engraftment are still unresolved issues. In the current study hNSCs derived from different brain regions were long-term expanded in vitro to yield proliferating neurospheres giving rise to neurons, astro-, and oligodendroglial cells and assessed for their potential for migration, differentiation, and anatomical integration following intracerebral grafting into rats. hNSCs isolated from neocortex, striatum, midbrain, and spinal cord (SC) proliferated following in vitro differentiation, and showed a significant decrease of newly formed neurons along the rostrocaudal axis of the developing central nervous system (CNS). Most of the mature neurons were positive for the neurotransmitter GABA. In vivo all cell types survived up to 9 weeks posttransplantation. Intrastriatally grafted hNSCs migrated extensively along white matter tracts reaching both rostral (forceps minor) and caudal (midbrain, cerebral peduncle) brain regions. The majority of migratory cells expressed the stem cell marker, nestin. A fraction of grafted cells acquired a neuronal phenotype expressing doublecortin, beta-III-tubulin, or GABA. These data demonstrate efficient in vitro propagation, region-specific long-term survival, long-distance migration, and neuronal differentiation of hNSCs after transplantation into the adult rat brain. The availability of a large pool of in vitro expanded nestin-positive cells offers the possibility for further ex vivo manipulations and the recruitment of different neuronal phenotypes for cell replacement strategies for CNS disorders.

  11. Visualization of damaged brain tissue after ischemic stroke with cobalt-55 positron emission tomography

    NARCIS (Netherlands)

    Jansen, H M; Pruim, J; vd Vliet, A M; Paans, A M; Hew, J M; Franssen, E J; de Jong, B M; Kosterink, J G; Haaxma, R; Korf, J

    UNLABELLED: In animal experiments, the radionuclide 55Co2+ has been shown to accumulate in degenerating cerebral tissue similar to Ca2+. METHODS: The potential role of 55Co2+ for in vivo brain PET imaging was investigated in four patients after ischemic stroke. RESULTS: PET showed uptake of 55Co2+

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

    Science.gov (United States)

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

    2017-12-01

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

  13. Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides.

    Directory of Open Access Journals (Sweden)

    Caghan Kizil

    Full Text Available Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI, RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs and identified two- polyR and Trans - that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael's addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues.

  14. Polychlorinated biphenyls in adipose tissue, liver, and brain from nine stillborns of varying gestational ages

    NARCIS (Netherlands)

    Huisman, M; Muskiet, FAJ; Van Der Paauw, CG; Essed, CE; Boersma, ER

    We analyzed polychlorinated biphenyls (PCBs) in s.c. adipose tissue, liver, and brain of nine fetuses who died in utero. Their median (range) gestational ages and birth weights were 34 (17-40) wk and 2050 (162-3225) g. Three fetuses were small for gestational age. The levels of PCB congener nos.

  15. Three levels of neuroelectronic interfacing: silicon chips with ion channels, nerve cells, and brain tissue.

    Science.gov (United States)

    Fromherz, Peter

    2006-12-01

    We consider the direct electrical interfacing of semiconductor chips with individual nerve cells and brain tissue. At first, the structure of the cell-chip contact is studied. Then we characterize the electrical coupling of ion channels--the electrical elements of nerve cells--with transistors and capacitors in silicon chips. On that basis it is possible to implement signal transmission between microelectronics and the microionics of nerve cells in both directions. Simple hybrid neuroelectronic systems are assembled with neuron pairs and with small neuronal networks. Finally, the interfacing with capacitors and transistors is extended to brain tissue cultured on silicon chips. The application of highly integrated silicon chips allows an imaging of neuronal activity with high spatiotemporal resolution. The goal of the work is an integration of neuronal network dynamics with digital electronics on a microscopic level with respect to experiments in brain research, medical prosthetics, and information technology.

  16. Computational Assessment of Neural Probe and Brain Tissue Interface under Transient Motion

    Directory of Open Access Journals (Sweden)

    Michael Polanco

    2016-06-01

    Full Text Available The functional longevity of a neural probe is dependent upon its ability to minimize injury risk during the insertion and recording period in vivo, which could be related to motion-related strain between the probe and surrounding tissue. A series of finite element analyses was conducted to study the extent of the strain induced within the brain in an area around a neural probe. This study focuses on the transient behavior of neural probe and brain tissue interface with a viscoelastic model. Different stages of the interface from initial insertion of neural probe to full bonding of the probe by astro-glial sheath formation are simulated utilizing analytical tools to investigate the effects of relative motion between the neural probe and the brain while friction coefficients and kinematic frequencies are varied. The analyses can provide an in-depth look at the quantitative benefits behind using soft materials for neural probes.

  17. Use of flow cytometry for high-throughput cell population estimates in brain tissue

    Science.gov (United States)

    Young, Nicole A.; Flaherty, David K.; Airey, David C.; Varlan, Peter; Aworunse, Feyi; Kaas, Jon H.; Collins, Christine E.

    2012-01-01

    The large size of primate brains is an impediment to obtaining high-resolution cell number maps of the cortex in humans and non-human primates. We present a rapid, flow cytometry-based cell counting method that can be used to estimate cell numbers from homogenized brain tissue samples comprising the entire cortical sheet. The new method, called the flow fractionator, is based on the isotropic fractionator (IF) method (Herculano-Houzel and Lent, 2005), but substitutes flow cytometry analysis for manual, microscope analysis using a Neubauer counting chamber. We show that our flow cytometry-based method for total cell estimation in homogenized brain tissue provides comparable data to that obtained using a counting chamber on a microscope. The advantages of the flow fractionator over existing methods are improved precision of cell number estimates and improved speed of analysis. PMID:22798947

  18. PIXE analysis of low concentration aluminum in brain tissues of an Alzheimer's disease patient

    Science.gov (United States)

    Ishihara, R.; Hanaichi, T.; Takeuchi, T.; Ektessabi, A. M.

    1999-06-01

    An excess accumulation and presence of metal ions may significantly alter a brain cell's normal functions. There have been increasing efforts in recent years to measure and quantify the density and distribution of excessive accumulations of constituent elements (such as Fe, Zn, Cu, and Ca) in the brain, as well as the presence and distribution of contaminating elements (such as Al). This is particularly important in cases of neuropathological disorders such as Alzheimer's disease, Parkinson's disease and ALS. The aim of this paper was to measure the Al present in the temporal cortex of the brain of an Alzheimer's disease patient. The specimens were taken from an unfixed autopsy brain which has been preserved for a period of 4 years in the deep freezer at -80 °C. Proton Induced X-ray Emission Spectroscopy was used for the measurement of Al concentration in this brain tissue. A tandem accelerator with 2 MeV of energy was also used. In order to increase the sensitivity of the signals in the low energy region of the spectra, the absorbers were removed. The results show that the peak height depends on the measurement site. However, in certain cases an extremely high concentration of Al was observed in the PIXE spectra, with an intensity higher than those in the other major elements of the brain's matrix element. Samples from tissues affected by the same disease were analyzed using the EDX analyzer. The results are quantitatively in very good agreement with those of the PIXE analysis.

  19. Perioperative period in cardiac transplantation from donors with brain death due to methanol poisoning

    Directory of Open Access Journals (Sweden)

    V. N. Poptsov

    2017-01-01

    Full Text Available The successful use of donor hearts from people died of methanol poisoning helps reducing the deficit of donor organs for patients requiring urgent cardiac transplantation [3]. We present our experience of successful cardiac transplantations from 2 donors who died due to methanol poisoning. Given the possibility of performing a cardiac transplant from this group of donors a protocol has been developed at the V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs of the Ministry of Healthcare of the Russian Federation which includes clinical, laboratory and instrumental criteria for the selection of heart donor and recipient. The possibility of delayed onset myocardial contractile dysfunction due to methanol poisoning means that a longer conditioningperiod is vital as well as compulsory clinical, laboratory and expert chocardiographic examinations of the potential donor heart.

  20. Value of routine angiography before traumatic lower-limb reconstruction with microvascular free tissue transplantation.

    Science.gov (United States)

    Lutz, B S; Ng, S H; Cabailo, R; Lin, C H; Wei, F C

    1998-04-01

    From November 1993 to June 1997, long-bone defects in 40 trauma patients were reconstructed with free osteoseptocutaneous fibula flaps. To determine the necessity of routine angiography in traumatized lower limbs before free flap transplantation, a prospective study was carried out. The study subjects were 34 patients, 25 males and 9 females, with an average age of 40.6 years. Reconstruction was performed primarily for bone defects after Gustillo type III b open fractures in 17 patients and secondarily for malunion and osteomyelitis in 17 patients. Reconstructed bone defects included 25 tibias and 9 femurs. Normal pedal pulses were palpable in 31 patients. Angiographic findings were abnormal in seven patients. In the three patients with abnormal pedal pulses, the particular nonpalpable pulses correlated with the vascular lesions shown in the angiograms (one in the tibial anterior artery and two in the tibial posterior artery). Four patients with either injury of the peroneal artery (three cases) or pseudoaneurysm of the tibial anterior artery (one case) had normal pedal pulses. In all patients, microvascular transplantations were performed successfully. Our study demonstrates the importance of thorough clinical evaluation. Preoperative angiography of the injured lower limbs did not provide relevant additional informations in this series. Familiarity with all available techniques makes it possible to cope with almost any difficult posttraumatic vascular condition. Routine recipient-site angiography before microsurgical reconstruction, therefore, seems unjustified.

  1. An endogenous inhibitor of cysteine cathepsin B from brain tissues

    Directory of Open Access Journals (Sweden)

    O.L. Lyanna

    2013-11-01

    -nitroanilide N,α-benzoyl-D,L-arginine. Using graphic methods for analysis of enzymatic kinetics we proposed a mechanism of interaction of the endogenous inhibitor with cysteine cathepsin B. This scheme could prove useful for the understanding of biochemical mechanisms occurring in normal and, especially, in pathological human brain processes.

  2. Guidelines for maintenance of adult patients with brain death and potential for multiple organ donations: the Task Force of the Brazilian Association of Intensive Medicine the Brazilian Association of Organs Transplantation, and the Transplantation Center of Santa Catarina.

    Science.gov (United States)

    Westphal, G A; Caldeira Filho, M; Fiorelli, A; Vieira, K D; Zaclikevis, V; Bartz, M; Wanzuita, R; Teixeira, C; Franke, C; Machado, F O; Friedman, G; Andrade, J; Matos, J D; Lamgaro, D M; Silva, E; Costa, G; Coelho, M E; Oliveira, M C; Youssef, N C M; Akamine, N; Duarte, P; Lisboa, R; Mazzali, M; Ferraz Neto, B H

    2012-10-01

    The organ shortage for transplantation, the principal factor that increases waiting lists, has become a serious public health problem. In this scenario, the intensivist occupies a prominent position as one of the professionals that first has a chance to identify brain death and to be responsible for the maintenance of the potential deceased donor. This report attempts to establish guidelines for care and maintenance of adult deceased donor organs guiding and standardizing care provided to patients with brain death. These guidelines were composed by intensivists, transplant coordinators, professionals from various transplant teams, and used transplant center. The formulated questions were forwarded to all members and recommendations were constructed after an extensive literature review selecting articles with the highest degree of evidence. Guidelines were developed in the form of questions reflecting frequent experiences in clinical intensive care practices. The main questions were: Is there an optimal interval for keeping organs of deceased donors viable? What actions are considered essential for maintaining deceased donors in this period? What are the limits of body temperature? How should the patient be warmed? Which laboratory tests should be performed? What is the collection interval? What are the limits in the laboratory and the capture scenario? What are the limits of blood pressure? When and how should one use catecholamines? This pioneer project involved a multidisciplinary team working in organ transplantation seeking to provide treatment guidance to increase the number of viable organs from deceased adult donors. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Carcinoma cells misuse the host tissue damage response to invade the brain

    Science.gov (United States)

    Chuang, Han-Ning; van Rossum, Denise; Sieger, Dirk; Siam, Laila; Klemm, Florian; Bleckmann, Annalen; Bayerlová, Michaela; Farhat, Katja; Scheffel, Jörg; Schulz, Matthias; Dehghani, Faramarz; Stadelmann, Christine; Hanisch, Uwe-Karsten; Binder, Claudia; Pukrop, Tobias

    2013-01-01

    The metastatic colonization of the brain by carcinoma cells is still barely understood, in particular when considering interactions with the host tissue. The colonization comes with a substantial destruction of the surrounding host tissue. This leads to activation of damage responses by resident innate immune cells to protect, repair, and organize the wound healing, but may distract from tumoricidal actions. We recently demonstrated that microglia, innate immune cells of the CNS, assist carcinoma cell invasion. Here we report that this is a fatal side effect of a physiological damage response of the brain tissue. In a brain slice coculture model, contact with both benign and malignant epithelial cells induced a response by microglia and astrocytes comparable to that seen at the interface of human cerebral metastases. While the glial damage response intended to protect the brain from intrusion of benign epithelial cells by inducing apoptosis, it proved ineffective against various malignant cell types. They did not undergo apoptosis and actually exploited the local tissue reaction to invade instead. Gene expression and functional analyses revealed that the C-X-C chemokine receptor type 4 (CXCR4) and WNT signaling were involved in this process. Furthermore, CXCR4-regulated microglia were recruited to sites of brain injury in a zebrafish model and CXCR4 was expressed in human stroke patients, suggesting a conserved role in damage responses to various types of brain injuries. Together, our findings point to a detrimental misuse of the glial damage response program by carcinoma cells resistant to glia-induced apoptosis. PMID:23832647

  4. Transplantation and Organ Donation in the Awareness of the Non-professional Public

    OpenAIRE

    Sládková, Andrea

    2014-01-01

    This bachelor thesis offers a complete overview of the tissue of organ donation and transplantation. The theoretical part contains information on the history of transplantation of vital organs. It describes the opportunities and risks of modern transplantology - the multicultural and ethical aspect. It covers activities of transplant centre and current legislation with emphasis on the criteria determination of brain death. Finally, it outlines the care of the potential donor and his/her loved...

  5. Zika Virus RNA Replication and Persistence in Brain and Placental Tissue

    Science.gov (United States)

    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

  6. A device for long-term perfusion, imaging, and electrical interfacing of brain tissue in vitro

    Directory of Open Access Journals (Sweden)

    Nathaniel J Killian

    2016-03-01

    Full Text Available Distributed microelectrode array (MEA recordings from consistent, viable, ≥ 500 µm thick tissue preparations over time periods from days to weeks may aid in studying a wide range of problems in neurobiology that require in vivo-like organotypic morphology. Existing tools for electrically interfacing with organotypic slices do not address necrosis that inevitably occurs within thick slices with limited diffusion of nutrients and gas, and limited removal of waste. We developed an integrated device that enables long-term maintenance of thick, functionally active, brain tissue models using interstitial perfusion and distributed recordings from thick sections of explanted tissue on a perforated multi-electrode array. This novel device allows for automated culturing, in situ imaging, and extracellular multi-electrode interfacing with brain slices, 3 D cell cultures, and potentially other tissue culture models. The device is economical, easy to assemble, and integrable with standard electrophysiology tools. We found that convective perfusion through the culture thickness provided a functional benefit to the preparations as firing rates were generally higher in perfused cultures compared to their respective unperfused controls. This work is a step towards the development of integrated tools for days-long experiments with more consistent, healthier, thicker, and functionally more active tissue cultures with built-in distributed electrophysiological recording and stimulation functionality. The results may be useful for the study of normal processes, pathological conditions, and drug screening strategies currently hindered by the limitations of acute (a few hours long brain slice preparations.

  7. Spatial mapping of drug delivery to brain tissue using hyperspectral spatial frequency-domain imaging

    Science.gov (United States)

    Singh-Moon, Rajinder P.; Roblyer, Darren M.; Bigio, Irving J.; Joshi, Shailendra

    2014-09-01

    We present an application of spatial frequency-domain imaging (SFDI) to the wide-field imaging of drug delivery to brain tissue. Measurements were compared with values obtained by a previously validated variation of diffuse reflectance spectroscopy, the method of optical pharmacokinetics (OP). We demonstrate a cross-correlation between the two methods for absorption extraction and drug concentration determination in both experimental tissue phantoms and freshly extracted rodent brain tissue. These methods were first used to assess intra-arterial (IA) delivery of cationic liposomes to brain tissue in Sprague Dawley rats under transient cerebral hypoperfusion. Results were found to be in agreement with previously published experimental data and pharmacokinetic models of IA drug delivery. We then applied the same scheme to evaluate IA mitoxantrone delivery to glioma-bearing rats. Good correlation was seen between OP and SFDI determined concentrations taken from normal and tumor averaged sites. This study shows the feasibility of mapping drug/tracer distributions and encourages the use of SFDI for spatial imaging of tissues for drug/tracer-tagged carrier deposition and pharmacokinetic studies.

  8. Limited predictability of postmortem human brain tissue quality by RNA integrity numbers.

    Science.gov (United States)

    Sonntag, Kai-C; Tejada, George; Subburaju, Sivan; Berretta, Sabina; Benes, Francine M; Woo, Tsung-Ung W

    2016-07-01

    The RNA integrity number (RIN) is often considered to be a critical measure of the quality of postmortem human brains. However, it has been suggested that RINs do not necessarily reflect the availability of intact mRNA. Using the Agilent bioanalyzer and qRT-PCR, we explored whether RINs provide a meaningful way of assessing mRNA degradation and integrity in human brain samples by evaluating the expression of 3'-5' mRNA sequences of the cytochrome C-1 (CYC1) gene. Analysis of electropherograms showed that RINs were not consistently correlated with RNA or cDNA profiles and appeared to be poor predictors of overall cDNA quality. Cycle thresholds from qRT-PCR analysis to quantify the amount of CYC1 mRNA revealed positive correlations of RINs with amplification of full-length transcripts, despite the variable degree of linear degradation along the 3'-5' sequence. These data demonstrate that in postmortem human brain tissue the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Quality assessment of postmortem human brains by RNA integrity numbers (RINs) may be misleading, as they do not measure intact mRNAs. We show that the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Our results resolve controversial assumption on interpreting quality assessments of human postmortem brains by RINs. © 2016 International Society for Neurochemistry.

  9. Position sensitive measurement of lithium traces in brain tissue with neutrons.

    Science.gov (United States)

    Lichtinger, Josef; Gernhäuser, Roman; Bauer, Andreas; Bendel, Michael; Canella, Lea; Graw, Matthias; Krücken, Reiner; Kudejova, Petra; Mützel, Elisabeth; Ring, Susanne; Seiler, Dominik; Winkler, Sonja; Zeitelhack, Karl; Schöpfer, Jutta

    2013-02-01

    The application of lithium is well known to have an antimanic-depressive effect, however, the influence it has on the human brain is still insufficiently known. The aim of our work is to develop a method to investigate the lithium concentration in the human brain with a very high sensitivity and a submillimeter resolution. Present methods either do not provide spatial resolution or are not sensitive enough to measure the naturally occurring lithium content in the human brain. Our method provides the opportunity to perform postmortem series measurements and obtain a detailed map of the lithium distribution in the human brain. This way possible correlations of the lithium distribution in the human brain and biological reasons for affective disorder can be clarified. To study the lithium distribution in different regions of the human brain the authors developed a method to measure lithium traces postmortem with a submillimeter spatial resolution using the neutron capture reaction (6)Li(n, α)(3)H. The lithium is measured by coincident detection of the alpha particles and tritons, emitted in opposite directions. The general concept, the preparation of the brain samples, the experimental setup at the measurement station of the Forschungs-Neutronenquelle Heinz Maier-Leibnitz, and a first measurement on human brain tissue are presented. A first measurement on a brain tissue sample nicely showed a spatial distribution of lithium down to a few hundreds of pg∕cm(3) with a maximal resolution of about σ(x) = σ(y) ≈ 200 μm. Also a direct correlation of lithium and optical tissue structure is observable. Typical measurement times of a few minutes allow for series measurements of up to 20 × 20 mm(2) large samples with a thickness of w = 10-20 μm in medical studies. The combination of a very high lithium sensitivity with position resolving measurement makes this method well suited for postmortem studies of the microscopic lithium distribution in the human brain and

  10. Evaluation of Raman spectra of human brain tumor tissue using the learning vector quantization neural network

    Science.gov (United States)

    Liu, Tuo; Chen, Changshui; Shi, Xingzhe; Liu, Chengyong

    2016-05-01

    The Raman spectra of tissue of 20 brain tumor patients was recorded using a confocal microlaser Raman spectroscope with 785 nm excitation in vitro. A total of 133 spectra were investigated. Spectra peaks from normal white matter tissue and tumor tissue were analyzed. Algorithms, such as principal component analysis, linear discriminant analysis, and the support vector machine, are commonly used to analyze spectral data. However, in this study, we employed the learning vector quantization (LVQ) neural network, which is typically used for pattern recognition. By applying the proposed method, a normal diagnosis accuracy of 85.7% and a glioma diagnosis accuracy of 89.5% were achieved. The LVQ neural network is a recent approach to excavating Raman spectra information. Moreover, it is fast and convenient, does not require the spectra peak counterpart, and achieves a relatively high accuracy. It can be used in brain tumor prognostics and in helping to optimize the cutting margins of gliomas.

  11. Fertility preservation among the cancer patients by ovarian tissue cryopreservation, transplantation, and follicular development.

    Science.gov (United States)

    Abedelahi, Ali; Rezaei-Tavirani, Mostafa; Mohammadnejad, Daryosh

    2013-01-01

    Ovarian tissue freezing or cryopreservation might be the only acceptable method for preserving the young women fertility, before radiotherapy or chemotherapy. This technology might be used for patients with recurrent ovarian cysts or endometriosis, without ovarian stimulation. Many efforts have made to improve cryopreservation conditions that should be seriously considered for cancer patients. Vitrification is a process which prevents ovarian tissue from cryo damage, then preserves cell viability. Both methods have used for evaluating not only the follicular development, but also the fertility after freezing and thawing. In this manuscript, we have discussed the techniques of ovarian tissue vitrification, then graft and maturation or follicular development is also mentioned.

  12. [REPAIR OF COMPOSITE TISSUE DEFECTS OF DORSAL THUMB INCLUDING INTERPHALANGEAL JOINT BY TRANSPLANTATION OF MODIFIED HALLUX TOE-NAIL COMPOSITE TISSUE FLAP].

    Science.gov (United States)

    Liu, Jinwei; He, Zaopeng; Li, Wei; Zhou, Congzhen; Zheng Yudong; Zeng, Difan; Liu, Dongbo

    2015-11-01

    To explore a new improved technique and its effectiveness to repair dorsal thumb composite tissue defects including interphalangeal joint by transplantation of modified hallux toe-nail composite tissue flap. The hallux toe-nail composite tissue flap carrying distal half hallux proximal phalanx, extensor hallucis longus, and interphalangeal joint capsule were designed and applied to repair the dorsal skin, nails, and interphalangeal joint defect of thumb in 14 cases between January 2007 and June 2013. They were all males, aged from 19 to 52 years (mean, 30 years). The time from injury to hospital was 0.5-2.0 hours (mean, 1.2 hours). The area of the thumb nail and dorsal skin defects ranged from 2.5 cm x 1.5 cm to 5.0 cm x 2.5 cm. The dorsal interphalangeal joint had different degrees of bone defect, with residual bone and joint capsule at the palm side. The length of bone defect ranged from 2.5 to 4.0 cm (mean, 3.4 cm). The hallux nail flap size ranged from 3.0 cm x 2.0 cm to 6.0 cm x 3.0 cm. The donor sites were repaired by skin grafting in 5 cases, and retrograde second dorsal metatarsal artery island flap in 9 cases. After operation, arterial crisis occurred in 1 case and the flap survived after relieving pressure; the other flaps survived, and wounds healed by first intention. Liquefaction necrosis of the skin grafting at donor site occurred in 3 cases, and the other skin grafting and all retrograde second dorsal metatarsal artery island flaps survived. The follow-up ranged from 9 months to 3 years and 6 months (mean, 23 months). The secondary plastic operation was performed in 4 cases at 6 months after operation because of slightly bulky composite tissue flaps. The other composite tissue flaps had good appearance, color, and texture. The growth of the nail was good in 12 cases, and slightly thickened in 2 cases. At last follow-up, X-ray examination showed that bone graft and proximal phalanx of the thumb had good bone healing in 12 cases. Good bone healing was

  13. Understanding the effect of corticosteroid pretreatment in brain-dead organ donors: new mechanistic insights for improvement of organ quality in liver transplantation.

    Science.gov (United States)

    Dahrenmöller, Carola; Reding, Raymond

    2017-09-15

    Transplant surgeons are currently faced with the challenge to accept marginal liver transplants due to steatosis or old age. Improving organ quality by implementing a selective organ protective donor management could be the first step towards a graft of enhanced quality. However, the molecular mechanisms of such treatments are still poorly understood. Glucocorticoid medication in donor medicine has been carried out and discussed for a long time. In a recent study published in Clinical Science , Jiménez-Castro et al. [Clin. Sci. (2017) 131, 733-746] demonstrate how liver histology and transplant liver function can be improved by administration of glucocorticoids to brain-dead donor rats with steatotic livers. This work illustrates the need for further trials in order to selectively improve the quality of steatotic livers with a potential for liver transplantation. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  14. Brain MR imaging abnormalities in pediatric patients after allogeneic bone marrow transplantation

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    Sally Emad-Eldin

    2014-12-01

    Conclusion: CNS complications after allogenic BMT in pediatric patients could cause a significant clinical problem. MRI can provide early diagnosis and follow-up to monitor treatment changes. Knowing the onset of the presentation of the complication in relation to the chronology of the transplant is important as it provides significant guidance on which causes to consider.

  15. Fertility Preservation Among the Cancer Patients by Ovarian Tissue Cryopreservation, Transplantation, and Follicular Development

    OpenAIRE

    Abedelahi, Ali; Rezaei-Tavirani, Mostafa; Mohammadnejad, Daryosh

    2013-01-01

    Ovarian tissue freezing or cryopreservation might be the only acceptable method for preserving the young women fertility, before radiotherapy or chemotherapy. This technology might be used for patients with recurrent ovarian cysts or endometriosis, without ovarian stimulation. Many efforts have made to improve cryopreservation conditions that should be seriously considered for cancer patients. Vitrification is a process which prevents ovarian tissue from cryo damage, then preserves cell viabi...

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

    Science.gov (United States)

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

    2012-02-01

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

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

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    Antony Harding

    2009-01-01

    Full Text Available 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.

  18. Effects of different concentrations of pollen extract on brain tissues of Oncorhynchus mykiss

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    Mehmet Fuat Gulhan

    2014-03-01

    Full Text Available Objective: To determine the antioxidant capacities of pollen extract applied at different concentrations on biochemical parameters in brain tissues of rainbow trouts. Methods: The effective concentration of pollen was determined with some biochemical parameters in brain tissues of fish treated at various concentrations of the pollen extract (0.5, 2.5, 5, 10, 20 and 30 mg/L for 96 h. The malondialdehyde levels, total antioxidant status, total oxidant status, oxidative stress index and amounts of total free sulfhydryl groups were analyzed in fish brain. Results: The malondialdehyde levels decreased in groups of 0.5, 2.5, 5, 10, 20 and 30 mg/L pollen-treated compared to control group (P<0.05. The highest level of total antioxidant status (P<0.05 and the lowest value (P<0.05 of the total oxidant status was 10 mg/L concentration of pollen. Oxidative stress index and level of sulfhydryl groups showed lowest values (P<0.05 in 10 mg/L pollen treated group compared with control group. Conclusions: To apply the pollen to fish reduces the detrimental effects and modulates oxidative status via activating antioxidant defense systems at brain tissue. As a result, pollen can be added up to 10 mg/L to the medium of rainbow trout to improve health of fish.

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

    Science.gov (United States)

    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

  20. Optical histology: a method to visualize microvasculature in thick tissue sections of mouse brain.

    Science.gov (United States)

    Moy, Austin J; Wiersma, Matthew P; Choi, Bernard

    2013-01-01

    The microvasculature is the network of blood vessels involved in delivering nutrients and gases necessary for tissue survival. Study of the microvasculature often involves immunohistological methods. While useful for visualizing microvasculature at the µm scale in specific regions of interest, immunohistology is not well suited to visualize the global microvascular architecture in an organ. Hence, use of immunohistology precludes visualization of the entire microvasculature of an organ, and thus impedes study of global changes in the microvasculature that occur in concert with changes in tissue due to various disease states. Therefore, there is a critical need for a simple, relatively rapid technique that will facilitate visualization of the microvascular network of an entire tissue. The systemic vasculature of a mouse is stained with the fluorescent lipophilic dye DiI using a method called "vessel painting". The brain, or other organ of interest, is harvested and fixed in 4% paraformaldehyde. The organ is then sliced into 1 mm sections and optically cleared, or made transparent, using FocusClear, a proprietary optical clearing agent. After optical clearing, the DiI-labeled tissue microvasculature is imaged using confocal fluorescence microscopy and adjacent image stacks tiled together to produce a depth-encoded map of the microvasculature in the tissue slice. We demonstrated that the use of optical clearing enhances both the tissue imaging depth and the estimate of the vascular density. Using our "optical histology" technique, we visualized microvasculature in the mouse brain to a depth of 850 µm. Presented here are maps of the microvasculature in 1 mm thick slices of mouse brain. Using combined optical clearing and optical imaging techniques, we devised a methodology to enhance the visualization of the microvasculature in thick tissues. We believe this technique could potentially be used to generate a three-dimensional map of the microvasculature in an entire

  1. Quantification of retinoid concentrations in human serum and brain tumor tissues.

    Science.gov (United States)

    Ali, Ramadan; Campos, Benito; Dyckhoff, Gerhard; Haefeli, Walter E; Herold-Mende, Christel; Burhenne, Jürgen

    2012-05-06

    Retinoic acid signaling is essential for central nervous system (CNS) differentiation and appears to be impaired in tumors. Thus far, there are no established methods to quantify relevant retinoids (all-trans-retinoic acid, 9-cis-retinoic acid, 13-cis retinoic acid, and retinol) in human brain tumors. We developed a single step extraction and quantification procedure for polar and apolar retinoids in normal tissue, lipid-rich brain tumor tissues, and serum. This quantification procedure is based on high performance liquid chromatography (HPLC) with diode-array detection (DAD) using all-trans-acitretin as an internal standard and extraction by liquid-liquid partition with ethyl acetate and borate buffer at pH 9. Recovery with this extraction procedure was higher than earlier (two-step) liquid-liquid extraction procedures based on hexane, NaOH, and HCl. The overall quantification procedure was validated according to Food and Drug Administration (FDA) guidelines and fulfilled all criteria of accuracy, precision, selectivity, recovery, and stability. The overall method accuracy varied between -5.6% and +5.4% for serum and -3.8% and +6.2% for tissues, and overall precision ranged from 3.1% to 6.9% for serum and 2.1% to 8.3% for tissues (%CV batch-to-batch). The lower limit of quantification for all compounds in tumor tissue (and serum) was 3.9 ng g(-1) (ng mL(-1)). Using this assay, photodegradation of the retinoids was evaluated and endogenous polar and apolar retinoids were quantified in sera and brain tumor tissues of patients and compared with serum and tonsil tissue concentrations of controls. It may thus serve as a suitable method for the characterization of retinoid uptake and metabolism in the respective compartments. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Optical histology: a method to visualize microvasculature in thick tissue sections of mouse brain.

    Directory of Open Access Journals (Sweden)

    Austin J Moy

    Full Text Available The microvasculature is the network of blood vessels involved in delivering nutrients and gases necessary for tissue survival. Study of the microvasculature often involves immunohistological methods. While useful for visualizing microvasculature at the µm scale in specific regions of interest, immunohistology is not well suited to visualize the global microvascular architecture in an organ. Hence, use of immunohistology precludes visualization of the entire microvasculature of an organ, and thus impedes study of global changes in the microvasculature that occur in concert with changes in tissue due to various disease states. Therefore, there is a critical need for a simple, relatively rapid technique that will facilitate visualization of the microvascular network of an entire tissue.The systemic vasculature of a mouse is stained with the fluorescent lipophilic dye DiI using a method called "vessel painting". The brain, or other organ of interest, is harvested and fixed in 4% paraformaldehyde. The organ is then sliced into 1 mm sections and optically cleared, or made transparent, using FocusClear, a proprietary optical clearing agent. After optical clearing, the DiI-labeled tissue microvasculature is imaged using confocal fluorescence microscopy and adjacent image stacks tiled together to produce a depth-encoded map of the microvasculature in the tissue slice. We demonstrated that the use of optical clearing enhances both the tissue imaging depth and the estimate of the vascular density. Using our "optical histology" technique, we visualized microvasculature in the mouse brain to a depth of 850 µm.Presented here are maps of the microvasculature in 1 mm thick slices of mouse brain. Using combined optical clearing and optical imaging techniques, we devised a methodology to enhance the visualization of the microvasculature in thick tissues. We believe this technique could potentially be used to generate a three-dimensional map of the

  3. Automatic tissue segmentation of neonate brain MR Images with subject-specific atlases

    Science.gov (United States)

    Cherel, Marie; Budin, Francois; Prastawa, Marcel; Gerig, Guido; Lee, Kevin; Buss, Claudia; Lyall, Amanda; Zaldarriaga Consing, Kirsten; Styner, Martin

    2015-03-01

    Automatic tissue segmentation of the neonate brain using Magnetic Resonance Images (MRI) is extremely important to study brain development and perform early diagnostics but is challenging due to high variability and inhomogeneity in contrast throughout the image due to incomplete myelination of the white matter tracts. For these reasons, current methods often totally fail or give unsatisfying results. Furthermore, most of the subcortical midbrain structures are misclassified due to a lack of contrast in these regions. We have developed a novel method that creates a probabilistic subject-specific atlas based on a population atlas currently containing a number of manually segmented cases. The generated subject-specific atlas is sharp and adapted to the subject that is being processed. We then segment brain tissue classes using the newly created atlas with a single-atlas expectation maximization based method. Our proposed method leads to a much lower failure rate in our experiments. The overall segmentation results are considerably improved when compared to using a non-subject-specific, population average atlas. Additionally, we have incorporated diffusion information obtained from Diffusion Tensor Images (DTI) to improve the detection of white matter that is not visible at this early age in structural MRI (sMRI) due to a lack of myelination. Although this necessitates the acquisition of an additional sequence, the diffusion information improves the white matter segmentation throughout the brain, especially for the mid-brain structures such as the corpus callosum and the internal capsule.

  4. Double in situ hybridization for microRNAs and mRNAs in brain tissues

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    Atsushi Kasai

    2016-11-01

    Full Text Available MicroRNAs (miRNAs participate in a variety of functions in the brain. Understanding the in vivo localization of miRNAs is an important step for uncovering their roles in brain function. However, the in situ detection of low-abundance miRNAs in brain tissues remains difficult and requires extensive optimization of in situ hybridization (ISH protocols in individual laboratories. Thus, detailed information regarding experimental conditions would serve as a useful reference for researchers in this field. Here, we investigated and summarized the effects of adjusting a series of critical steps, including tissue fixation, probe accessibility and hybridization stringency, to standardize the currently used miRNA ISH procedures. As a result, we successfully detected several low-abundance miRNAs by ISH using the following experimental conditions: (1 use of fresh brain tissues, (2 digestion of brain samples with proteinase K, (3 LNA-probe hybridization at a temperature 37°C below the melting temperature of the RNA, (4 performance of high-stringency wash steps using 50% formamide in 1× standard saline citrate (SSC buffer. RT-PCR of the punched-out tissues using TaqManTM primers confirmed the ISH results. Finally, double-fluorescence ISH successfully demonstrated the colocalization of miRNAs and mRNAs. Thus, the detailed information regarding the miRNA ISH procedures used in this study may help to resolve the technical hurdles observed in the in vivo localization of miRNAs, and the elucidation of the specific roles of miRNAs.

  5. Neutrophil depletion reduces edema formation and tissue loss following traumatic brain injury in mice

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    Kenne Ellinor

    2012-01-01

    Full Text Available Abstract Background Brain edema as a result of secondary injury following traumatic brain injury (TBI is a major clinical concern. Neutrophils are known to cause increased vascular permeability leading to edema formation in peripheral tissue, but their role in the pathology following TBI remains unclear. Methods In this study we used controlled cortical impact (CCI as a model for TBI and investigated the role of neutrophils in the response to injury. The outcome of mice that were depleted of neutrophils using an anti-Gr-1 antibody was compared to that in mice with intact neutrophil count. The effect of neutrophil depletion on blood-brain barrier function was assessed by Evan's blue dye extravasation, and analysis of brain water content was used as a measurement of brain edema formation (24 and 48 hours after CCI. Lesion volume was measured 7 and 14 days after CCI. Immunohistochemistry was used to assess cell death, using a marker for cleaved caspase-3 at 24 hours after injury, and microglial/macrophage activation 7 days after CCI. Data were analyzed using Mann-Whitney test for non-parametric data. Results Neutrophil depletion did not significantly affect Evan's blue extravasation at any time-point after CCI. However, neutrophil-depleted mice exhibited a decreased water content both at 24 and 48 hours after CCI indicating reduced edema formation. Furthermore, brain tissue loss was attenuated in neutropenic mice at 7 and 14 days after injury. Additionally, these mice had a significantly reduced number of activated microglia/macrophages 7 days after CCI, and of cleaved caspase-3 positive cells 24 h after injury. Conclusion Our results suggest that neutrophils are involved in the edema formation, but not the extravasation of large proteins, as well as contributing to cell death and tissue loss following TBI in mice.

  6. Measuring the linear and nonlinear elastic properties of brain tissue with shear waves and inverse analysis.

    Science.gov (United States)

    Jiang, Yi; Li, Guoyang; Qian, Lin-Xue; Liang, Si; Destrade, Michel; Cao, Yanping

    2015-10-01

    We use supersonic shear wave imaging (SSI) technique to measure not only the linear but also the nonlinear elastic properties of brain matter. Here, we tested six porcine brains ex vivo and measured the velocities of the plane shear waves induced by acoustic radiation force at different states of pre-deformation when the ultrasonic probe is pushed into the soft tissue. We relied on an inverse method based on the theory governing the propagation of small-amplitude acoustic waves in deformed solids to interpret the experimental data. We found that, depending on the subjects, the resulting initial shear modulus [Formula: see text] varies from 1.8 to 3.2 kPa, the stiffening parameter [Formula: see text] of the hyperelastic Demiray-Fung model from 0.13 to 0.73, and the third- [Formula: see text] and fourth-order [Formula: see text] constants of weakly nonlinear elasticity from [Formula: see text]1.3 to [Formula: see text]20.6 kPa and from 3.1 to 8.7 kPa, respectively. Paired [Formula: see text] test performed on the experimental results of the left and right lobes of the brain shows no significant difference. These values are in line with those reported in the literature on brain tissue, indicating that the SSI method, combined to the inverse analysis, is an efficient and powerful tool for the mechanical characterization of brain tissue, which is of great importance for computer simulation of traumatic brain injury and virtual neurosurgery.

  7. Brain tissue partial pressure of oxygen predicts the outcome of severe traumatic brain injury under mild hypothermia treatment

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    Sun H

    2016-08-01

    Full Text Available Hongtao Sun,1,* Maohua Zheng,2,* Yanmin Wang,1 Yunfeng Diao,1 Wanyong Zhao,1 Zhengjun Wei1 1Sixth Department of Neurosurgery, Affiliated Hospital of Logistics University of People’s Armed Police Force, Tianjin, 2Department of Neurosurgery, The First Hospital of Lanzhou University, Lanzhou, People’s Republic of China *These authors contributed equally to this work Objective: The aim of this study was to investigate the clinical significance and changes of brain tissue partial pressure of oxygen (PbtO2 in the course of mild hypothermia treatment (MHT for treating severe traumatic brain injury (sTBI. Methods: There were 68 cases with sTBI undergoing MHT. PbtO2, intracranial pressure (ICP, jugular venous oxygen saturation (SjvO2, and cerebral perfusion pressure (CPP were continuously monitored, and clinical outcomes were evaluated using the Glasgow Outcome Scale score. Results: Of 68 patients with sTBI, PbtO2, SjvO2, and CPP were obviously increased, but decreased ICP level was observed throughout the MHT. PbtO2 and ICP were negatively linearly correlated, while there was a positive linear correlation between PbtO2 and SjvO2. Monitoring CPP and SjvO2 was performed under normal circumstances, and a large proportion of patients were detected with low PbtO2. Decreased PbtO2 was also found after MHT. Conclusion: Continuous PbtO2 monitoring could be introduced to evaluate the condition of regional cerebral oxygen metabolism, thereby guiding the clinical treatment and predicting the outcome. Keywords: severe traumatic brain injury, hypothermia, brain tissue partial pressure of oxygen, therapy

  8. Importance of good manufacturing practices in microbiological monitoring in processing human tissues for transplant.

    Science.gov (United States)

    Pianigiani, Elisa; Ierardi, Francesca; Fimiani, Michele

    2013-12-01

    Skin allografts represent an important therapeutic resource in the treatment of severe skin loss. The risk associated with application of processed tissues in humans is very low, however, human material always carries the risk of disease transmission. To minimise the risk of contamination of grafts, processing is carried out in clean rooms where air quality is monitored. Procedures and quality control tests are performed to standardise the production process and to guarantee the final product for human use. Since we only validate and distribute aseptic tissues, we conducted a study to determine what type of quality controls for skin processing are the most suitable for detecting processing errors and intercurrent contamination, and for faithfully mapping the process without unduly increasing production costs. Two different methods for quality control were statistically compared using the Fisher exact test. On the basis of the current study we selected our quality control procedure based on pre- and post-processing tissue controls, operator and environmental controls. Evaluation of the predictability of our control methods showed that tissue control was the most reliable method of revealing microbial contamination of grafts. We obtained 100 % sensitivity by doubling tissue controls, while maintaining high specificity (77 %).

  9. The effect of cortisol in rat steatotic and non-steatotic liver transplantation from brain-dead donors.

    Science.gov (United States)

    Jiménez-Castro, Mónica B; Negrete-Sánchez, Elsa; Casillas-Ramírez, Araní; Gulfo, Jose; Álvarez-Mercado, Ana I; Cornide-Petronio, María Eugenia; Gracia-Sancho, Jordi; Rodés, Juan; Peralta, Carmen

    2017-04-25

    In the present study, we examined the effects of cortisol on steatotic and non-steatotic liver grafts from brain-dead donors and characterized the underlying mechanisms involved. Non-steatotic liver grafts showed reduced cortisol and increased cortisone levels in association with up-regulation of enzymes that inactivate cortisol. Conversely, steatotic liver grafts exhibited increased cortisol and reduced cortisone levels. The enzymes involved in cortisol generation were overexpressed, and those involved in cortisol inactivation or clearance were down-regulated in steatotic liver grafts. Exogenous administration of cortisol negatively affected hepatic damage and survival rate in non-steatotic liver transplantation (LT); however, cortisol treatment up-regulated the phosphoinositide 3-kinase (PI3K)-protein kinase C (PKC) pathway, resulting in protection against the deleterious effects of brain-dead donors on damage and inflammatory response in steatotic LT as well as in increased survival of recipients. The present study highlights the differences in the role of cortisol and hepatic mechanisms that regulate cortisol levels based on the type of liver. Our findings suggest that cortisol treatment is a feasible and highly protective strategy to reduce the adverse effects of brain-dead donor livers in order to ultimately improve liver graft quality in the presence of steatosis, whereas cortisol treatment would not be recommended for non-steatotic liver grafts. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

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

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, John, E-mail: jmweaver@salud.unm.edu [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Yang, Yirong [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Purvis, Rebecca [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Weatherwax, Theodore [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Rosen, Gerald M. [Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, MD 21201 (United States); Center for EPR Imaging In Vivo Physiology, University of Maryland, Baltimore, MD 21201 (United States); Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201 (United States); Liu, Ke Jian [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)

    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 tissue 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

  11. Nanofibrous gelatine scaffolds integrated with nerve growth factor-loaded alginate microspheres for brain tissue engineering.

    Science.gov (United States)

    Büyüköz, Melda; Erdal, Esra; Alsoy Altinkaya, Sacide

    2016-11-12

    Neural regeneration research is designed in part to develop strategies for therapy after nerve damage due to injury or disease. In this study, a new gelatine-based biomimetic scaffold was fabricated for brain tissue engineering applications. A technique combining thermally induced phase separation and porogen leaching was used to create interconnected macropores and nanofibrous structure. To promote tissue regeneration processes, the scaffolds were integrated with nerve growth factor (NGF)-loaded alginate microspheres. The results showed that nanofibrous matrix could only be obtained when gelatine concentration was at least 7.5% (w/v). The scaffold with a modulus value (1.2 kPa) similar to that of brain tissue (0.5-1 kPa) was obtained by optimizing the heat treatment time, macropore size and gelatine concentration. The encapsulation efficiencies of NGF into 0.1% and 1% alginate microspheres were 85% and 100%, respectively. The release rate of NGF from the microspheres was controlled by the alginate concentration and the poly(L-lysine) coating. The immobilization of the microspheres in the scaffold reduced burst release and significantly extended the release period. The nanofibrous architecture and controlled release of NGF from the microspheres induced neurite extension of PC12 cells, demonstrating that the released NGF was in an active form. The results suggest that the scaffolds prepared in this study may have potential applications in brain tissue engineering due to topologic and mechanical properties similar to brain tissue and pore structure suitable for cell growth and differentiation. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Transplantation of Bioprinted Tissues and Organs: Technical and Clinical Challenges and Future Perspectives.

    Science.gov (United States)

    Ravnic, Dino J; Leberfinger, Ashley N; Koduru, Srinivas V; Hospodiuk, Monika; Moncal, Kazim K; Datta, Pallab; Dey, Madhuri; Rizk, Elias; Ozbolat, Ibrahim T

    2017-07-01

    : Three-dimensional (3D) bioprinting is a revolutionary technology in building living tissues and organs with precise anatomic control and cellular composition. Despite the great progress in bioprinting research, there has yet to be any clinical translation due to current limitations in building human-scale constructs, which are vascularized and readily implantable. In this article, we review the current limitations and challenges in 3D bioprinting, including in situ techniques, which are one of several clinical translational models to facilitate the application of this technology from bench to bedside. A detailed discussion is made on the technical barriers in the fabrication of scalable constructs that are vascularized, autologous, functional, implantable, cost-effective, and ethically feasible. Clinical considerations for implantable bioprinted tissues are further expounded toward the correction of end-stage organ dysfunction and composite tissue deficits.

  13. Outcomes of transplantations of cryopreserved ovarian tissue to 41 women in Denmark

    DEFF Research Database (Denmark)

    Jensen, A K; Kristensen, S G; Macklon, K T

    2015-01-01

    with a pregnancy-wish. WHAT IS KNOWN ALREADY: Cryopreservation of ovarian tissue is now gaining ground as a valid method for fertility preservation. More than 36 children worldwide have now been born following this procedure. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study of 41 women who had...... by monitoring relapse in cancer survivors. MAIN RESULTS, AND THE ROLE OF CHANCE: Among 32 women with a pregnancy-wish, 10 (31%) had a child/children (14 children in total); this included 1 woman with a third trimester on-going pregnancy. In addition, two legal abortions and one second trimester miscarriage...... when the tissue became non-functional. WIDER IMPLICATIONS OF THE FINDINGS: Cryopreservation of ovarian tissue is likely to become integrated into the treatment of young women, with cancer, who run a risk of losing their fertility. The full functional lifespan of grafts is still being evaluated, because...

  14. Differential gene expression in brain tissues of aggressive and non-aggressive dogs

    Directory of Open Access Journals (Sweden)

    Tverdal Aage

    2010-06-01

    Full Text Available Abstract Background Canine behavioural problems, in particular aggression, are important reasons for euthanasia of otherwise healthy dogs. Aggressive behaviour in dogs also represents an animal welfare problem and a public threat. Elucidating the genetic background of adverse behaviour can provide valuable information to breeding programs and aid the development of drugs aimed at treating undesirable behaviour. With the intentions of identifying gene-specific expression in particular brain parts and comparing brains of aggressive and non-aggressive dogs, we studied amygdala, frontal cortex, hypothalamus and parietal cortex, as these tissues are reported to be involved in emotional reactions, including aggression. Based on quantitative real-time PCR (qRT-PCR in 20 brains, obtained from 11 dogs euthanised because of aggressive behaviour and nine non-aggressive dogs, we studied expression of nine genes identified in an initial screening by subtraction hybridisation. Results This study describes differential expression of the UBE2V2 and ZNF227 genes in brains of aggressive and non-aggressive dogs. It also reports differential expression for eight of the studied genes across four different brain tissues (amygdala, frontal cortex, hypothalamus, and parietal cortex. Sex differences in transcription levels were detected for five of the nine studied genes. Conclusions The study showed significant differences in gene expression between brain compartments for most of the investigated genes. Increased expression of two genes was associated with the aggression phenotype. Although the UBE2V2 and ZNF227 genes have no known function in regulation of aggressive behaviour, this study contributes to preliminary data of differential gene expression in the canine brain and provides new information to be further explored.

  15. Immunohistochemical and histochemical analysis of newly formed tissues in root canal space transplanted with dental pulp stem cells plus platelet-rich plasma.

    Science.gov (United States)

    Zhu, Xiaofei; Wang, Yu; Liu, Yuan; Huang, George T-J; Zhang, Chengfei

    2014-10-01

    Tissue regeneration in root canals after pulpectomy can be achieved by transplantation of autologous dental pulp stem cells and/or platelet-rich plasma. However, the identity of the newly formed tissue in the pulp space has been only examined by histologic analysis. This study aimed to apply immunohistochemistry and histochemistry to detect specific markers in the newly generated tissues after root canal regenerative treatment. In our previous study, 32 root canals in 4 mature dogs were treated with a pulp regeneration procedure after pulpectomy using either blood clot, transplantation of dental pulp stem cells, platelet-rich plasma, or a combination of cells and plasma. In the present study, the tissues were examined for the expression of periostin to detect periodontal ligament tissue, nestin and dentin sialoprotein for odontoblasts, and bone sialoprotein and osteocalcin for bone tissues. Samples were also stained for tartrate-resistant acid phosphatase (TRAP) as a marker for osteoclastic lineages. Continuous periostin-positive tissue was observed extending from the periodontal ligament into the inner canal surface in which the mineral islands were surrounded by weak periostin staining. There was also positive staining for TRAP, bone sialoprotein, and osteocalcin in the canal space, suggesting the presence of bone tissue. A layer of mineralized tissue along the inner surface of the root canal was negative for TRAP, suggesting the tissue likely to be cementum. In all samples, no nestin-positive reaction was observed, whereas dentin sialoprotein was detected in PDL, dentinal tubules, and intracanal fibrous tissues. There was no difference between any of the 4 groups. The tissues formed in the dog mature root canals after regenerative endodontic procedures are not pulp tissues but mainly periodontal tissues. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  16. Successful renal transplantation from a brain-dead deceased donor with head injury, disseminated intravascular coagulation and deranged renal functions

    Directory of Open Access Journals (Sweden)

    P P Ghuge

    2013-01-01

    Full Text Available Deceased donors (DDs with the brain death due to head injury are the major source of organs for transplantation. The incidence of post-head injury disseminated intravascular coagulation (DIC ranges from 24% to 50%. Many centers do not accept organs from donors with DIC due to increased risk of primary graft non-function and/or high chances of morbidity/mortality. We performed two successful renal transplants from a DD with head injury with DIC and deranged renal function. One of the recipients developed transient thrombocytopenia, but there was no evidence of DIC or delayed graft functions in either of the recipients. Over a follow-up of 1 month, both are doing well with stable graft function and hematological profile. Thus, a carefully selected DD with severe DIC even with deranged renal function is not a contraindication for organ donation if other risk factors for primary non-function are excluded. This approach will also help in overcoming organ shortage.

  17. Cryopreservation of porcine fetal ventral mesencephalic tissue for intrastriatal transplantation in Parkinson's disease

    NARCIS (Netherlands)

    Koopmans, J.; Hogenesch, I.; Copray, S.; Middel, B.; van Dijk, H.; Go, K-G.; Staal, M.

    2001-01-01

    In this study we examined the efficacy of cryopreserving porcine fetal mesencephalic tissue. After microscopical dissection of the ventral mesencephalon (VM) from E28 pig fetuses, the collection of explants was randomly divided into two equal parts. One part was directly prepared as cell suspension.

  18. Epileptic rat brain tissue analyzed by 2D correlation Raman spectroscopy

    Science.gov (United States)

    Sacharz, Julia; Wesełucha-Birczyńska, Aleksandra; Zięba-Palus, Janina; Lewandowski, Marian H.; Kowalski, Rafał; Palus, Katarzyna; Chrobok, Łukasz; Moskal, Paulina; Birczyńska, Malwina; Sozańska, Agnieszka

    2018-01-01

    Absence epilepsy is the neurological disorder characterized by the pathological spike-and wave discharges present in the electroencephalogram, accompanying a sudden loss of consciousness. Experiments were performed on brain slices obtained from young male WAG/Rij rats (2-3 weeks old), so that they were sampled before the appearance of brain-damaging seizures symptoms. Two differing brain areas of the rats' brain tissue were studied: the somatosensory cortex (Sc) and the dorsal lateral geniculate nucleus of the thalamus (DLG). The Raman spectra of the fresh brain scraps, kept during measurements in artificial cerebrospinal fluid, were collected using as an excitation source 442 nm, 514.5 nm, 785 nm and 1064 nm laser line. The average spectra were analyzed by 2D correlation method regarding laser line as an external perturbation. In 2D synchronous spectra positive auto-peaks corresponding to the Cdbnd C stretching and amide I band vibrations show maxima at 1660 cm- 1 and 1662 cm- 1 for Sc and DLG, respectively. The prominent auto-peak at 2937 cm- 1, originated from the CH3 mode in DLG brain area, seems to indicate the importance of methylation, considered to be significant in epileptogenesis. Synchronous and asynchronous correlations peaks, glutamic acid and gamma-aminobutyric acid (GABA), appear in Sc and DLG, respectively. In the 1730-1600 cm- 1 range occur cross-peaks which appearance might be triggered by glial fibrillary acidic protein (GFAP) activation.

  19. Hypercoagulation following brain death cannot be reversed by the neutralization of systemic tissue factor.

    Science.gov (United States)

    Hvas, Christine L; Fenger-Eriksen, Christian; Høyer, Søren; Sørensen, Benny; Tønnesen, Else

    2013-08-01

    Cerebral injury and brain death is associated with apparent hypercoagulation and poor organ outcome. This experimental study challenges the hypotheses that i) brain death causes hypercoagulation and microvascular thrombosis and that ii) neutralizing systemic tissue factor (TF) by in vitro addition of a TF inhibitor (recombinant active site-inhibited factor VIIa (ASIS)) can reverse the hypercoagulable profile. Using a validated pig model of intracranial hemorrhage and brain death, 20 pigs were randomized to either control or brain death. The primary endpoints were coagulation parameters measured with whole blood thromboelastometry (ROTEM), thrombin generation and a porcine TF-sensitive plasma clotting time assay. In vitro spiking experiments with ASIS were performed in parallel with the latter two assessments. The kidneys were examined histologically for microvascular thromboses. Brain death induced hypercoagulation, as demonstrated with ROTEM, thrombin generation, and reduced TF-sensitive plasma clotting time. In vitro inhibition of TF with ASIS did not reverse the hypercoagulation. No microvascular thromboses were found in the kidneys. Brain death causes hypercoagulation; however, inhibition of TF does not reverse the coagulopathy. Thus, TF release does not seem to be the primary cause of this hypercoagulation. Minor changes in the levels of protein C suggest that the protein C pathway may be linked to the observed coagulopathy. © 2013.

  20. [Changes of MDA, SOD, TNF-alpha, and IL-1beta in rat brain tissue after concussion].

    Science.gov (United States)

    Gao, Feng; Zhao, Li; Gu, Zhen-Yong; Cong, Bin

    2014-02-01

    To observe the changes of malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) in rat brain tissue and to explore the mechanism of secondary cerebral injury after brain concussion. The brain concussion model was established with the pathological changes of rat brain tissue by Weil stain. The expressions of MDA and SOD in brain tissue were examined by photochemical method. The expressions of TNF-alpha and IL-1beta in cerebral cortex and hippocampus were examined by immunochemistry. Nerve myelin sheath showed disorder, disruption, gryposis and swelling by Weil stain. Above changes were more severe at 12h. The quantity of MDA in rat brain tissue after concussion was significantly higher than that in the control group. The activity of SOD was significantly lower than that in the control group. The expressions of TNF-alpha and IL-1beta increased more significantly in cerebral cortex and hippocampus in rat brain tissue after concussion than that in the control group. Oxidative stress and inflammatory injury in the rat brain tissue, which may play an important role in secondary cerebral injury after concussion.

  1. Microinjection of membrane-impermeable molecules into single neural stem cells in brain tissue.

    Science.gov (United States)

    Wong, Fong Kuan; Haffner, Christiane; Huttner, Wieland B; Taverna, Elena

    2014-05-01

    This microinjection protocol allows the manipulation and tracking of neural stem and progenitor cells in tissue at single-cell resolution. We demonstrate how to apply microinjection to organotypic brain slices obtained from mice and ferrets; however, our technique is not limited to mouse and ferret embryos, but provides a means of introducing a wide variety of membrane-impermeable molecules (e.g., nucleic acids, proteins, hydrophilic compounds) into neural stem and progenitor cells of any developing mammalian brain. Microinjection experiments are conducted by using a phase-contrast microscope equipped with epifluorescence, a transjector and a micromanipulator. The procedure normally takes ∼2 h for an experienced researcher, and the entire protocol, including tissue processing, can be performed within 1 week. Thus, microinjection is a unique and versatile method for changing and tracking the fate of a cell in organotypic slice culture.

  2. Identifying signature Zernike modes for efficient light delivery through brain tissue

    CERN Document Server

    Sane, Sharmila; Lee, Woei Ming; Stricker, Christian; Bachor, Hans; Daria, Vincent

    2015-01-01

    Recent progress in neuroscience to image and investigate brain function has been made possible by impressive developments in optogenetic and opto-molecular tools. Such research requires advances in optical techniques for the delivery of light through brain tissue with high spatial resolution. The tissue causes distortions of the wavefront of the incoming light which broadens the focus, thereby reducing the intensity and resolution especially in techniques requiring focal illumination. Adaptive wavefront correction has been demonstrated to compensate for these distortions. However, in many situations iterative derivation of the corrective wavefront introduces time constraints that limit its usefulness when used to probe living cells. Here we demonstrate a direct and fast technique by working with a small set of Zernike modes and demonstrate that corrections derived a priori can lead to significant improvement of the focus. We verify this idea by the electrical response of whole-cell patched neurons following t...

  3. Increased expression of tissue cytokines in graft-versus-host disease after small bowel transplantation in the rat.

    Science.gov (United States)

    Koide, S; McVay, L D; Frankel, W L; Behling, C A; Zhou, E D; Shimada, T; Zhang, W; Rombeau, J L

    1997-08-15

    Graft-versus-host disease (GVHD) occurs in the recipient after small bowel transplantation (SBT). Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin 6 (IL-6), may be important mediators of GVHD. Increased expression of these cytokines might precede the clinical manifestations of GVHD induced by SBT. Heterotopic SBT was performed using Lewis donors into Lewis x Brown Norway F1 (LBN-F1) recipients. The isograft control was performed from LBN-F1 into LBN-F1. Animals were killed on the 5th and 11th postoperative day (POD). mRNA was isolated from recipient native small bowel, colon, spleen, liver, and mesenteric lymph nodes and from nonsurgical controls as baseline. Semiquantitative reverse transcriptase polymerase chain reaction was performed to amplify mRNA transcripts for TNF-alpha, IFN-gamma, and IL-6 using alpha32P-dATP incorporation. Clinical signs, histologic assessment, and cytokine expression were correlated. On POD 5, there were neither clinical signs nor histologic features of GVHD, but mRNA expression of TNF-alpha and IL-6 in small bowel, IL-6 in spleen, and IFN-gamma in mesenteric lymph nodes were significantly increased in allograft animals when compared with normal and isograft tissues. On POD 11, both the clinical signs and histologic features of GVHD were seen, and TNF-alpha and IL-6 in native small bowel, TNF-alpha in colon, IFN-gamma in spleen, and IL-6 in mesenteric lymph nodes were significantly increased in allograft animals when compared with that in normal and isograft tissues. In conclusion, TNF-alpha, IFN-gamma, and IL-6 expression precede clinical onset and histologic evidence of GVHD in specific tissues. Therefore, increased expression of these cytokines is correlated with the development of GVHD in this model of SBT.

  4. Anomalous frequency-dependent ionic conductivity of lesion-laden human-brain tissue

    Science.gov (United States)

    Emin, David; Akhtari, Massoud; Fallah, Aria; Vinters, Harry V.; Mathern, Gary W.

    2017-10-01

    We study the effect of lesions on our four-electrode measurements of the ionic conductivity of (˜1 cm3) samples of human brain excised from patients undergoing pediatric epilepsy surgery. For most (˜94%) samples, the low-frequency ionic conductivity rises upon increasing the applied frequency. We attributed this behavior to the long-range (˜0.4 mm) diffusion of solvated sodium cations before encountering intrinsic impenetrable blockages such as cell membranes, blood vessels, and cell walls. By contrast, the low-frequency ionic conductivity of some (˜6%) brain-tissue samples falls with increasing applied frequency. We attribute this unusual frequency-dependence to the electric-field induced liberation of sodium cations from traps introduced by the unusually severe pathology observed in samples from these patients. Thus, the anomalous frequency-dependence of the ionic conductivity indicates trap-producing brain lesions.

  5. Characterisation of new monoclonal antibodies reacting with prions from both human and animal brain tissues

    DEFF Research Database (Denmark)

    Cordes, H.; Bergstrom, A.L.; Ohm, J.

    2008-01-01

    Post-mortem diagnosis of transmissible spongiform encephalopathies (prion diseases) is primarily based on the detection of a protease resistant, misfolded disease associated isoform (PrP(Sc)) of the prion protein (PrP(C)) on neuronal cells. These methods depend on antibodies directed against Pr......-type mice and used for western blotting and immunohistochemistry to detect several types of human prion-disease associated PrP(Sc), including sporadic Creutzfeldt-Jakob Disease (CJD) (subtypes MM1 and VV2), familial CJD and Gerstmann-Straussler-Scheinker (GSS) disease PrP(Sc) as well as PrP(Sc) of bovine...... spongiform encephalopathy (bovine brain), scrapie (ovine brain) and experimental scrapie in hamster and in mice. The antibodies were also used for PET-blotting in which PrP(Sc) blotted from brain tissue sections onto a nitrocellulose membrane is visualized with antibodies after protease and denaturant...

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

    Science.gov (United States)

    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.

  7. Fertility preservation and refreezing of transplanted ovarian tissue-a potential new way of managing patients with low risk of malignant cell recurrence

    DEFF Research Database (Denmark)

    Kristensen, Stine Gry; Giorgione, Veronica; Humaidan, Peter

    2017-01-01

    OBJECTIVE: To report the first successful refreezing of ovarian tissue recovered more than 3 years after transplantation in a woman previously treated for early-stage ovarian cancer. DESIGN: Evaluation of cryopreserved and grafted ovarian tissue. SETTING: University hospital. PATIENT(S): A 23-year-old...... of functional follicles than previously estimated can actually support ovarian function. Removing and refreezing grafted tissue could be a new way of handling not only cancer patients with a risk of malignant cell recurrence, but also certain groups of patients with genetic conditions....

  8. Regional distribution of opiate alkaloids in experimental animals' brain tissue and blood

    Directory of Open Access Journals (Sweden)

    Đurendić-Brenesel Maja

    2012-01-01

    Full Text Available The aim of this study was to examine the regional distribution of opiate alkaloids from seized heroin in experimental animals' brain regions and blood. Results could be used in the examination of opiate alkaloids' distribution in human biological samples in order to contribute to the solution of the causes of death due to heroin intake. Experimental animals (Wistar rats were treated with seized heroin, and were sacrificed at different time periods: 5, 15, 45 and 120 min after treatment. Opiate alkaloids' (codeine, morphine, acetylcodeine, 6- acetylmorphine and 3,6-diacetylmorphine content was determined in the brain regions (cortex, brainstem, amygdala and basal ganglia and blood of animals using gas chromatography-mass spectrometry (GC-MS method. The highest content of opiate alkaloids in the blood was measured 15 min, and in the brain tissue 45 min after the treatment with heroin. The maximal concentration of opiates was determined in the basal ganglia. The obtained results offer the possibility of selecting this part of the brain tissue as a representative sample for identifying and assessing the content of opiates.

  9. 2D correlation Raman microspectroscopy of chosen parts of rat's brain tissue

    Science.gov (United States)

    Zięba-Palus, J.; Wesełucha-Birczyńska, A.; Sacharz, J.; Lewandowski, M. H.; Palus, K.; Chrobok, Ł.; Kowalski, R.; Moskal, P.; Birczyńska, M.; Sozańska, Agnieszka

    2017-11-01

    Raman spectra of two areas of Wistar rat brain tissue, tissue that are linked functionally to one another -the somatosensory cortex (Sc) and the dorsolateral geniculate nucleus of the thalamus (DLG)- excited with 442 nm, 514.5 nm, 785 nm and 1064 nm laser lines- were studied. No fixation method was used to preserve samples taken from the precisely defined anatomical areas of the brain. The brain slides were kept in artificial cerebrospinal fluid during the measurements. Averaged spectra were analyzed using the 2D correlation method. The varying wavelength/energy of the excitation laser was regarded as an external stimulus. 2D correlation analysis resolved differences between Sc and DLG in the range of 1800-1000 cm-1 and also in the hetero-spectral regions of about 1800-1200 cm-1 and 3100-2500 cm-1. Auto-peaks at 1659 cm-1 and 1666 cm-1 characterize the phase of the constituent lipid clusters with proteins and cholesterol in Sc and cholesterol in DLG, respectively. Appearing cross-peaks indicate the correlations with different phospholipids structures and protein bands and also cholesterol for Sc and DLG, respectively. Asynchronous spectra distinguish between areas of the brain due to the presence of neurotransmitters.

  10. Multigrid Nonlocal Gaussian Mixture Model for Segmentation of Brain Tissues in Magnetic Resonance Images

    Directory of Open Access Journals (Sweden)

    Yunjie Chen

    2016-01-01

    Full Text Available We propose a novel segmentation method based on regional and nonlocal information to overcome the impact of image intensity inhomogeneities and noise in human brain magnetic resonance images. With the consideration of the spatial distribution of different tissues in brain images, our method does not need preestimation or precorrection procedures for intensity inhomogeneities and noise. A nonlocal information based Gaussian mixture model (NGMM is proposed to reduce the effect of noise. To reduce the effect of intensity inhomogeneity, the multigrid nonlocal Gaussian mixture model (MNGMM is proposed to segment brain MR images in each nonoverlapping multigrid generated by using a new multigrid generation method. Therefore the proposed model can simultaneously overcome the impact of noise and intensity inhomogeneity and automatically classify 2D and 3D MR data into tissues of white matter, gray matter, and cerebral spinal fluid. To maintain the statistical reliability and spatial continuity of the segmentation, a fusion strategy is adopted to integrate the clustering results from different grid. The experiments on synthetic and clinical brain MR images demonstrate the superior performance of the proposed model comparing with several state-of-the-art algorithms.

  11. Effect of ginkgolide B on brain metabolism and tissue oxygenation in severe haemorrhagic stroke.

    Science.gov (United States)

    Chi, Chun-Ling; Shen, Dong-Fang; Wang, Peng-Jun; Li, Hu-Lun; Zhang, Li

    2015-01-01

    Ginkgolide B, a diterpene, is an herbal constituent isolated from the leaves of Ginkgo biloba tree. The present study demonstrates the effect of ginkgolide B in osmotherapy on brain metabolism and tissue oxygenation. Multimodality monitoring including intracranial pressure (ICP), cerebral perfusion pressure (CPP), partial pressure of brain tissue oxygen (PbtO2), lactate/pyruvate ratio (LPR) and microdialysis were employed to study the effect of ginkgolide B osmotherapy. The results demonstrated that administration of 15% solution of ginkgolide B to the comatose patients with raised ICP (> 20 mm Hg) and resistant to standard therapy led to a significant decrease in ICP. The cerebral microdialysis was used to compare mean arterial blood pressure (MAP), ICP, CPP, PbtO2, brain lactate, pyruvate and glucose level after hourly intervals starting 3 h before and up to 4 h after hyperosmolar therapy. There was a decrease in ICP in 45 min from 23 ± 14 mm Hg (P therapy. Also the brain glucose remained unaffected.

  12. Super resolution imaging of genetically labelled synapses in Drosophila brain tissue

    Directory of Open Access Journals (Sweden)

    Isabelle Ayumi Spühler

    2016-05-01

    Full Text Available Understanding synaptic connectivity and plasticity within brain circuits and their relationship to learning and behavior is a fundamental quest in neuroscience. Visualizing the fine details of synapses using optical microscopy remains however a major technical challenge. Super resolution microscopy opens the possibility to reveal molecular features of synapses beyond the diffraction limit. With direct stochastic optical reconstruction microscopy, dSTORM, we image synaptic proteins in the brain tissue of the fruit fly, Drosophila melanogaster. Super resolution imaging of brain tissue harbors difficulties due to light scattering and the density of signals. In order to reduce out of focus signal, we take advantage of the genetic tools available in the Drosophila and have fluorescently tagged synaptic proteins expressed in only a small number of neurons. These neurons form synapses within the calyx of the mushroom body, a distinct brain region involved in associative memory formation. Our results show that super resolution microscopy, in combination with genetically labelled synaptic proteins, is a powerful tool to investigate synapses in a quantitative fashion providing an entry point for studies on synaptic plasticity during learning and memory formation

  13. Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Lanekoff, Ingela T.; Thomas, Mathew; Carson, James P.; Smith, Jordan N.; Timchalk, Charles; Laskin, Julia

    2013-01-15

    Imaging mass spectrometry offers simultaneous detection of drugs, drug metabolites and endogenous substances in a single experiment. This is important when evaluating effects of a drug on a complex organ system such as the brain, where there is a need to understand how regional drug distribution impacts function. Nicotine is an addictive drug and its action in the brain is of high interest. Here we use nanospray desorption electrospray ionization, nano-DESI, imaging to discover the localization of nicotine in rat brain tissue after in vivo administration of nicotine. Nano-DESI is a new ambient technique that enables spatially-resolved analysis of tissue samples without special sample pretreatment. We demonstrate high sensitivity of nano-DESI imaging that enables detection of only 0.7 fmole nicotine per pixel in the complex brain matrix. Furthermore, by adding deuterated nicotine to the solvent, we examined how matrix effects, ion suppression, and normalization affect the observed nicotine distribution. Finally, we provide preliminary results suggesting that nicotine localizes to the hippocampal substructure called dentate gyrus.

  14. Alteration of amino acid neurotransmitters in brain tissues of immature rats treated with realgar.

    Science.gov (United States)

    Huo, Taoguang; Chang, Bei; Zhang, Yinghua; Chen, Zaixing; Li, Weikai; Jiang, Hong

    2012-01-05

    Realgar is a traditional Chinese medicine, which has been used for thousands of years and are claimed to have therapeutic effects. The toxicity from realgar or realgar-containing traditional medicines has raised public concern. However, the neurotoxicity induced by realgar is less reported. Amino acid neurotransmitters are closely linked to the vulnerability of the immature brain to neuronal injury. The investigation of amino acid neurotransmitters is important to understand the evolution of developmental brain damage. An improved HPLC-UV method was developed and applied to analyzing amino acid neurotransmitters of aspartate, glutamate, glutamine, homocysteine, serine, glycine, γ-aminobutyric acid and taurine in brain tissues of immature rats after the treatment of realgar. Significant changes of these amino acid neurotransmitters were observed in realgar treated groups. Negative correlations were found between the levels of some amino acids and the contents of arsenic in brain tissues. The result indicates that the neurotoxicity induced by realgar is associated with its effects on amino acid neurotransmitters. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Mechanical Characterization of Brain Tissue in Compression at Dynamic Strain Rates

    CERN Document Server

    Rashid, Badar; Gilchrist, Michael; 10.1016/j.jmbbm.2012.01.022

    2013-01-01

    Traumatic brain injury (TBI) occurs when local mechanical load exceeds certain tolerance levels for brain tissue. Extensive research has been done previously for brain matter experiencing compression at quasistatic loading; however, limited data is available to model TBI under dynamic impact conditions. In this research, an experimental setup was developed to perform unconfined compression tests and stress relaxation tests at strain rates < 90/s. The brain tissue showed a stiffer response with increasing strain rates, showing that hyperelastic models are not adequate. Specifically, the compressive nominal stress at 30% strain was 8.83 +/- 1.94, 12.8 +/- 3.10 and 16.0 +/- 1.41 kPa (mean +/- SD) at strain rates of 30, 60 and 90/s, respectively. Relaxation tests were also conducted at 10%-50% strain with the average rise time of 10 ms, which can be used to derive time dependent parameters. Numerical simulations were performed using one-term Ogden model with initial shear modulus mu_0 = 6.06 +/- 1.44, 9.44 +/-...

  16. Determining the presence of periodontopathic virulence factors in short-term postmortem Alzheimer's disease brain tissue.

    Science.gov (United States)

    Poole, Sophie; Singhrao, Sim K; Kesavalu, Lakshmyya; Curtis, Michael A; Crean, StJohn

    2013-01-01

    The aim of this study was to establish a link between periodontal disease and Alzheimer's disease (AD) with a view to identifying the major periodontal disease bacteria (Treponema denticola, Tannerella forsythia, and Porphyromonas gingivalis) and/or bacterial components in brain tissue from 12 h postmortem delay. Our request matched 10 AD cases for tissue from Brains for Dementia Research alongside 10 non-AD age-related controls with similar or greater postmortem interval. We exposed SVGp12, an astrocyte cell line, to culture supernatant containing lipopolysaccharide (LPS) from the putative periodontal bacteria P. gingivalis. The challenged SVGp12 cells and cryosections from AD and control brains were immunolabeled and immunoblotted using a battery of antibodies including the anti-P. gingivalis-specific monoclonal antibody. Immunofluorescence labeling demonstrated the SVGp12 cell line was able to adsorb LPS from culture supernatant on its surface membrane; similar labeling was observed in four out of 10 AD cases. Immunoblotting demonstrated bands corresponding to LPS from P. gingivalis in the SVGp12 cell lysate and in the same four AD brain specimens which were positive when screened by immunofluorescence. All controls remained negative throughout while the same four cases were consistently positive for P. gingivalis LPS (p = 0.029). This study confirms that LPS from periodontal bacteria can access the AD brain during life as labeling in the corresponding controls, with equivalent/longer postmortem interval, was absent. Demonstration of a known chronic oral-pathogen-related virulence factor reaching the human brains suggests an inflammatory role in the existing AD pathology.

  17. Diagnostic value of MRS-quantified brain tissue lactate level in identifying children with mitochondrial disorders

    Energy Technology Data Exchange (ETDEWEB)

    Lunsing, Roelineke J.; Strating, Kim [University Medical Centre Groningen, University of Groningen, Department of Child Neurology, Groningen (Netherlands); Koning, Tom J. de [University Medical Centre Groningen, University of Groningen, Department of Pediatric Metabolic Diseases, Groningen (Netherlands); Sijens, Paul E. [University Medical Centre Groningen, University of Groningen, Department of Radiology, Groningen (Netherlands)

    2017-03-15

    Magnetic resonance spectroscopy (MRS) of children with or without neurometabolic disease is used for the first time for quantitative assessment of brain tissue lactate signals, to elaborate on previous suggestions of MRS-detected lactate as a marker of mitochondrial disease. Multivoxel MRS of a transverse plane of brain tissue cranial to the ventricles was performed in 88 children suspected of having neurometabolic disease, divided into 'definite' (n = 17, ≥1 major criteria), 'probable' (n = 10, ≥2 minor criteria), 'possible' (n = 17, 1 minor criterion) and 'unlikely' mitochondrial disease (n = 44, none of the criteria). Lactate levels, expressed in standardized arbitrary units or relative to creatine, were derived from summed signals from all voxels. Ten 'unlikely' children with a normal neurological exam served as the MRS reference subgroup. For 61 of 88 children, CSF lactate values were obtained. MRS lactate level (>12 arbitrary units) and the lactate-to-creatine ratio (L/Cr >0.22) differed significantly between the definite and the unlikely group (p = 0.015 and p = 0.001, respectively). MRS L/Cr also differentiated between the probable and the MRS reference subgroup (p = 0.03). No significant group differences were found for CSF lactate. MRS-quantified brain tissue lactate levels can serve as diagnostic marker for identifying mitochondrial disease in children. (orig.)

  18. Protein analysis through Western blot of cells excised individually from human brain and muscle tissue.

    Science.gov (United States)

    Koob, A O; Bruns, L; Prassler, C; Masliah, E; Klopstock, T; Bender, A

    2012-06-15

    Comparing protein levels from single cells in tissue has not been achieved through Western blot. Laser capture microdissection allows for the ability to excise single cells from sectioned tissue and compile an aggregate of cells in lysis buffer. In this study we analyzed proteins from cells excised individually from brain and muscle tissue through Western blot. After we excised individual neurons from the substantia nigra of the brain, the accumulated surface area of the individual cells was 120,000, 24,000, 360,000, 480,000, 600,000 μm2. We used an optimized Western blot protocol to probe for tyrosine hydroxylase in this cell pool. We also took 360,000 μm2 of astrocytes (1700 cells) and analyzed the specificity of the method. In muscle we were able to analyze the proteins of the five complexes of the electron transport chain through Western blot from 200 human cells. With this method, we demonstrate the ability to compare cell-specific protein levels in the brain and muscle and describe for the first time how to visualize proteins through Western blot from cells captured individually. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. [LINGO-1 expression of brain tissue in experimental autoimmune encephalomyelitis mouse].

    Science.gov (United States)

    Wang, Chunjuan; Guo, Shougang; Qu, Chuanqiang; Zhang, Jie; Fu, Peicai; Tang, Ronghua

    2014-04-22

    To observe the changes of LINGO-1 expression with time after onset in EAE mouse. C57/BL6 mice were completely randomly divided into EAE model group (n = 15) , adjuvant group (n = 15) and control group (n = 15) .LINGO-1 expression of brain tissue was detected on day 1, 7, 14, 21 and 30 after onset by RT-PCR and Western blot.RhoA and p-RhoA expression of brain tissue was analysed by Western blot. The LINGO-1mRNA levels in EAE model group were markedly higher than control group on day 1, 7and 14 after onset (4.63 ± 0.25, 2.72 ± 0.12, 1.98 ± 0.16, P Lingo-1 mRNA was close to control group.Expression levels of Lingo-1 protein on day 1, 7, 14, 21, 30 were higher than control group (2.11 ± 0.15, 3.15 ± 0.09, 2.45 ± 0.12, 1.89 ± 0.17, 1.21 ± 0.05, P LINGO-1 expression of brain tissue of EAE mouse upregulates and changes with time after onset, which may inhibit myelination by RhoA activation.In clinic, the antagonist of LINGO-1 for MS should be applied as soon as possible.

  20. Surgical illustration of en-bloc (dual) kidney transplant from a 16-month old brain-dead donor to an adult recipient.

    Science.gov (United States)

    Jain, Vikas; Jain, Saurabh; Singhal, Paras; Nayak, Suman Lata; Mathur, Rajendra P

    2017-01-01

    Transplantable organs from pediatric donors have been contributing significantly to donor pool worldwide. Pediatric donors are excellent resources that should be procured whenever available, and with the recent increase in deceased donations in India, more pediatric donors will be available for organ harvesting. We share a rare instance of multi-organ harvesting from a 16-month old brain dead donor and implanting both kidneys en-bloc in an adult male, while liver went to a 4-year old child. The report provides the surgical illustration of salient steps of transplanting both kidneys from pediatric donor into an adult, in an en-bloc manner.

  1. Transplantation of adipose tissue-derived stem cells improves cardiac contractile function and electrical stability in a rat myocardial infarction model.

    Science.gov (United States)

    Gautam, Milan; Fujita, Daiki; Kimura, Kazuhiro; Ichikawa, Hinako; Izawa, Atsushi; Hirose, Masamichi; Kashihara, Toshihide; Yamada, Mitsuhiko; Takahashi, Masafumi; Ikeda, Uichi; Shiba, Yuji

    2015-04-01

    The transplantation of adipose tissue-derived stem cells (ADSCs) improves cardiac contractility after myocardial infarction (MI); however, little is known about the electrophysiological consequences of transplantation. The purpose of this study was to clarify whether the transplantation of ADSCs increases or decreases the incidence of ventricular tachyarrhythmias (VT) in a rat model of MI. MI was induced experimentally by permanent occlusion of the left anterior descending artery of Lewis rats. ADSCs were harvested from GFP-transgenic rats, and were cultured until passage four. ADSCs (10×10(6)) resuspended in 100μL saline or pro-survival cocktail (PSC), which enhances cardiac graft survival, were injected directly into syngeneic rat hearts 1week after MI. The recipients of ADSCs suspended in PSC had a larger graft area compared with those receiving ASDCs suspended in saline at 1week post-transplantation (number of graft cells/section: 148.7±10.6 vs. 22.4±3.4, ptransplanted with ASDCs in PSC. ADSCs were transplanted into infarcted hearts, and the mechanical and electrophysiological functions were assessed. Echocardiography revealed that ADSC recipients had improved contractile function compared with those receiving PSC vehicle (fractional shortening: 21.1±0.9 vs. 14.1±1.2, ptransplantation, VT was induced via in vivo programmed electrical stimulation. The recipients of ADSCs showed a significantly lower incidence of induced VT compared with the control (31.3% vs. 83.3%, ptransplantation, we performed ex vivo optical mapping using a voltage sensitive dye, and found that ADSC transplantation decreased conduction velocity and its dispersion in the peri-infarct area. These results suggest that ADSC transplantation improved cardiac mechanical and electrophysiological functions in subacute MI. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Co-transplantation of fetal bone tissue facilitates the development and reconstitution in human B cells in humanized NOD/SCID/IL-2Rγnull (NSG) mice.

    Science.gov (United States)

    Kim, Miyoung; Choi, Bongkum; Kim, So Yong; Yang, Ji-Hyuk; Roh, Cheong Rae; Lee, Ki-Young; Kim, Sung Joo

    2011-08-01

    In terms of the function and reconstitution efficacy of human immune cells, co-transplantation of human fetal tissues, such as thymus and liver, with CD34(+) hematopoietic stem cells (HSCs) has potential advantages in the generation of humanized mice. To examine the effects of bone tissues in the reconstitution of human immune cells, particularly in B cells, we generated a new humanized mice co-transplanted with human fetal thymus (hFT)/fetal bone (hFB) tissues and human fetal liver-derived CD34(+) cells. Humanized mice exhibited effective reconstitution of human immune cells earlier compared to control humanized mice. In terms of quantity, the number of immune cells, such as human T, B, and monocyte/macrophages was significantly increased. Furthermore, significant increase of B cell progenitors and immature/naïve B cells could be detected in the bone marrow and spleen of humanized mice. Our results demonstrate that co-transplantation of hFB tissue may facilitate the reconstitution of human B and T cells, and therefore the humanized model may be used to develop therapeutic human antibodies for clinical use.

  3. Restoration of ovarian activity and pregnancy after transplantation of cryopreserved ovarian tissue

    DEFF Research Database (Denmark)

    Donnez, Jacques; Dolmans, Marie-Madeleine; Pellicer, Antonio

    2013-01-01

    to preserve fertility in cancer patients. The present review reports the results of 60 orthotopic reimplantations of cryopreserved ovarian tissue performed by three teams, as well as 24 live births reported in the literature to date. Restoration of ovarian activity occurred in almost all cases in the three...... series. Among the 60 patients, eleven conceived and six of those had already delivered twelve healthy babies. In the future, we are looking to: 1) improve freezing techniques; and 2) enhance the "vascular bed" before reimplantation to increase pregnancy rates. On the other hand, cryopreservation...

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

    Science.gov (United States)

    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

  5. Expression of defective measles virus genes in brain tissues of patients with subacute sclerosing panencephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Baczko, K.; Liebert, U.G.; Billeter, M.; Cattaneo, R.; Budka, H.; Ter Meulen, V.

    1986-08-01

    The persistence of measles virus in selected areas of the brains of four patients with subacute sclerosing panencephalitis (SSPE) was characterized by immunohistological and biochemical techniques. The five measles virus structural proteins were never simultaneously detectable in any of the bran sections. Nucleocapsid proteins and phosphoproteins were found in every diseased brain area, whereas hemagglutinin protein was detected in two cases, fusion protein was detected in three cases, and matrix protein was detected in only one case. Also, it could be shown that the amounts of measles virus RNA in the brains differed from patient to patient and in the different regions investigated. In all patients, plus-strand RNAs specific for these five viral genes could be detected. However, the amounts of fusion and hemagglutinin mRNAs were low compared with the amounts in lytically infected cells. The presence of particular measles virus RNAs in SSPE-infected brains did not always correlate with mRNA activity. In in vitro translations, the matrix protein was produced in only one case, and the hemagglutinin protein was produced in none. These results indicate that measles virus persistence in SSPE is correlated with different defects of several genes which probably prevent assembly of viral particles in SSPE-infected brain tissue.

  6. A Genotype Resource for Postmortem Brain Samples from the Autism Tissue Program

    Science.gov (United States)

    Wintle, Richard F.; Lionel, Anath C.; Hu, Pingzhao; Ginsberg, Stephen D.; Pinto, Dalila; Thiruvahindrapduram, Bhooma; Wei, John; Marshall, Christian R.; Pickett, Jane; Cook, Edwin H.; Scherer, Stephen W.

    2015-01-01

    The Autism Tissue Program (ATP), a science program of Autism Speaks, provides researchers with access to well-characterized postmortem brain tissues. Researchers access these tissues through a peer-reviewed, project-based approval process, and obtain related clinical information from a secure, online informatics portal. However, few of these samples have DNA banked from other sources (such as a blood sample from the same individual), hindering genotype–phenotype correlation and interpretation of gene expression data derived fromthe banked brain tissue. Here, we describe an initiative to extract DNA from Brodmann Area 19, and genotype these samples using both the Affymetrix Genome-Wide Human SNP Array 6.0 and the Illumina Human1M-Duo DNA Analysis BeadChip genome-wide microarray technologies. We additionally verify reported gender, and infer ethnic background from the single nucleotide polymorphism data. We have also used a rigorous, multiple algorithm approach to identify genomic copy number variation (CNV) from these array data. Following an initial proof of principle study using two samples, 52 experimental samples, consisting of 27 subjects with confirmed or suspected autism and related disorders, 5 subjects with cytogenetically visible duplications of 15q, 2 with epilepsy and 18 age-matched normal controls were processed, yielding high-quality genotype data in all cases. The genotype and CNV data are provided via the ATP informatics portal as a resource for the autism research community. PMID:21254448

  7. Tissue-specific interferon alpha subtype response to SIV infection in brain, spleen, and lung.

    Science.gov (United States)

    Zaritsky, Luna Alammar; Dery, Alicia; Leong, Wan Yee; Gama, Lucio; Clements, Janice E

    2013-01-01

    Interferon alpha (IFNalpha) is a type I interferon that plays a major role in host defense. There are 13 different IFNalpha genes in humans, but much of the work concerning their role in viral defense has been limited to studying either subtype 2 or pan IFNalpha due to the inability to distinguish between highly similar genetic and amino acid sequences. Because of recent advances in molecular and biochemical techniques, it is possible to study the regulation of individual subtypes. It has been reported that HIV/SIV infection results in impaired IFNalpha responses in certain tissues. Using a pigtailed macaque SIV model, we examined the subtype response during acute infection in 3 tissues that are known to be infected with HIV/SIV, but whose IFNalpha subtype response has not been extensively studied: the brain, spleen, and lung. We found that the expression and regulation of specific subtypes occur in a tissue-specific manner. There was more limited IFNalpha subtype expression in the lung and brain, where predominantly macrophages are infected compared to the spleen, which contains both infected CD4+ lymphocytes and macrophages. Understanding the IFNalpha subtype response in tissues known to be infected with HIV/SIV can help tailor adjunctive treatment regimens to highly active antiretroviral therapy.

  8. Heterotopically transplanted CVO neural stem cells generate neurons and migrate with SVZ cells in the adult mouse brain.

    Science.gov (United States)

    Bennett, Lori B; Cai, Jingli; Enikolopov, Grigori; Iacovitti, Lorraine

    2010-05-07

    Production of new neurons throughout adulthood has been well characterized in two brain regions, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus. The neurons produced from these regions arise from neural stem cells (NSCs) found in highly regulated stem cell niches. We recently showed that midline structures called circumventricular organs (CVOs) also contain NSCs capable of neurogenesis and/or astrogliogenesis in vitro and in situ (Bennett et al.). The present study demonstrates that NSCs derived from two astrogliogenic CVOs, the median eminence and organum vasculosum of the lamina terminalis of the nestin-GFP mouse, possess the potential to integrate into the SVZ and differentiate into cells with a neuronal phenotype. These NSCs, following expansion and BrdU-labeling in culture and heterotopic transplantation into a region proximal to the SVZ in adult mice, migrate caudally to the SVZ and express early neuronal markers (TUC-4, PSA-NCAM) as they migrate along the rostral migratory stream. CVO-derived BrdU(+) cells ultimately reach the olfactory bulb where they express early (PSA-NCAM) and mature (NeuN) neuronal markers. Collectively, these data suggest that although NSCs derived from the ME and OVLT CVOs are astrogliogenic in situ, they produce cells phenotypic of neurons in vivo when placed in a neurogenic environment. These findings may have implications for neural repair in the adult brain. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  9. Promotion of Survival and Engraftment of Transplanted Adipose Tissue-Derived Stromal and Vascular Cells by Overexpression of Manganese Superoxide Dismutase

    Directory of Open Access Journals (Sweden)

    Silvia Baldari

    2016-07-01

    Full Text Available Short-term persistence of transplanted cells during early post-implant period limits clinical efficacy of cell therapy. Poor cell survival is mainly due to the harsh hypoxic microenvironment transplanted cells face at the site of implantation and to anoikis, driven by cell adhesion loss. We evaluated the hypothesis that viral-mediated expression of a gene conferring hypoxia resistance to cells before transplant could enhance survival of grafted cells in early stages after implant. We used adipose tissue as cell source because it consistently provides high yields of adipose-tissue-derived stromal and vascular cells (ASCs, suitable for regenerative purposes. Luciferase positive cells were transduced with lentiviral vectors expressing either green fluorescent protein as control or human manganese superoxide dismutase (SOD2. Cells were then exposed in vitro to hypoxic conditions, mimicking cell transplantation into an ischemic site. Cells overexpressing SOD2 displayed survival rates significantly greater compared to mock transduced cells. Similar results were also obtained in vivo after implantation into syngeneic mice and assessment of cell engraftment by in vivo bioluminescent imaging. Taken together, these findings suggest that ex vivo gene transfer of SOD2 into ASCs before implantation confers a cytoprotective effect leading to improved survival and engraftment rates, therefore enhancing cell therapy regenerative potential.

  10. X-ray diffraction from intact tau aggregates in human brain tissue

    Energy Technology Data Exchange (ETDEWEB)

    Landahl, Eric C.; Antipova, Olga; Bongaarts, Angela; Barrea, Raul; Berry, Robert; Binder, Lester I.; Irving, Thomas; Orgel, Joseph; Vana, Laurel; Rice, Sarah E. (DePaul); (IIT); (NWU)

    2011-09-15

    We describe an instrument to record X-ray diffraction patterns from diseased regions of human brain tissue by combining an in-line visible light fluorescence microscope with an X-ray diffraction microprobe. We use thiazine red fluorescence to specifically label and detect the filamentous tau protein pathology associated with Pick's disease, as several laboratories have done previously. We demonstrate that thiazine red-enhanced regions within the tissue show periodic structure in X-ray diffraction, which is not observed in healthy tissue. One observed periodicity (4.2 {angstrom}) is characteristic of cross-beta sheet structure, consistent with previous results from powder diffraction studies performed on purified, dried tau protein.

  11. X-ray diffraction from intact tau aggregates in human brain tissue

    Energy Technology Data Exchange (ETDEWEB)

    Landahl, Eric C. [DePaul University, Department of Physics, 2219 N. Kenmore Ave., IL 60614, Chicago (United States); Antipova, Olga [Illinois Institute of Technology, Department of Biological Chemical and Physical Sciences, 3101 South Dearborn St., IL 60616, Chicago (United States); Bongaarts, Angela [Northwestern University, Department of Cell and Molecular Biology, 303 E. Chicago Ave., IL 60611, Chicago (United States); Barrea, Raul [Illinois Institute of Technology, Department of Biological Chemical and Physical Sciences, 3101 South Dearborn St., IL 60616, Chicago (United States); Berry, Robert; Binder, Lester I. [Northwestern University, Department of Cell and Molecular Biology, 303 E. Chicago Ave., IL 60611, Chicago (United States); Irving, Thomas; Orgel, Joseph [Illinois Institute of Technology, Department of Biological Chemical and Physical Sciences, 3101 South Dearborn St., IL 60616, Chicago (United States); Vana, Laurel [Northwestern University, Department of Cell and Molecular Biology, 303 E. Chicago Ave., IL 60611, Chicago (United States); Rice, Sarah E., E-mail: s-rice@northwestern.edu [Northwestern University, Department of Cell and Molecular Biology, 303 E. Chicago Ave., IL 60611, Chicago (United States)

    2011-09-01

    We describe an instrument to record X-ray diffraction patterns from diseased regions of human brain tissue by combining an in-line visible light fluorescence microscope with an X-ray diffraction microprobe. We use thiazine red fluorescence to specifically label and detect the filamentous tau protein pathology associated with Pick's disease, as several laboratories have done previously. We demonstrate that thiazine red-enhanced regions within the tissue show periodic structure in X-ray diffraction, which is not observed in healthy tissue. One observed periodicity (4.2 A) is characteristic of cross-beta sheet structure, consistent with previous results from powder diffraction studies performed on purified, dried tau protein.

  12. Innate immune activation by tissue injury and cell death in the setting of hematopoietic stem cell transplantation.

    Science.gov (United States)

    Brennan, Todd V; Rendell, Victoria R; Yang, Yiping

    2015-01-01

    Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) with donor lymphocyte infusion is the mainstay of treatment for many types of hematological malignancies, but the therapeutic effect and prevention of relapse is complicated by donor T-cell recognition and attack of host tissue in a process known as graft-versus-host disease (GvHD). Cytotoxic myeloablative conditioning regimens used prior to Allo-HSCT result in the release of endogenous innate immune activators that are increasingly recognized for their role in creating a pro-inflammatory milieu. This increased inflammatory state promotes allogeneic T-cell activation and the induction and perpetuation of GvHD. Here, we review the processes of cellular response to injury and cell death that are relevant following Allo-HSCT and present the current evidence for a causative role of a variety of endogenous innate immune activators in the mediation of sterile inflammation following Allo-HSCT. Finally, we discuss the potential therapeutic strategies that target the endogenous pathways of innate immune activation to decrease the incidence and severity of GvHD following Allo-HSCT.

  13. Arthroscopic treatment of chondral defects in the hip: AMIC, MACI, microfragmented adipose tissue transplantation (MATT and other options

    Directory of Open Access Journals (Sweden)

    Jannelli Eugenio

    2017-01-01

    Full Text Available Chondral lesions are currently considered in the hip as a consequence of trauma, osteonecrosis, dysplasia, labral tears, loose bodies, dislocation, previous slipped capital femoral epiphysis and Femoro-Acetabular-Impingement (FAI. The management of chondral lesions is debated and several techniques are described. The physical examination must be carefully performed, followed by radiographs and magnetic resonance imaging (MRI. Differential diagnosis with other pathologies must be considered. Debridement is indicated in patients younger than 50 years with a chondropathy of 1st or 2nd degree. Microfractures are indicated in patients younger than 50 years with a chondropathy of 3rd or 4th degree less than 2 cm2. Matrix-Induced Autologous Chondrocyte Implantation (MACI and Autologous Matrix-Induced Chondrogenesis (AMIC procedures are indicated in patients with full-thickness symptomatic 3rd–4th degree chondral defects, extended 2 cm2 or more. The AMIC procedure has the advantage of a one-step procedure and much less expense. Microfragmented adipose tissue transplantation (MATT is indicated for the treatment of delamination and 1st and 2nd degree chondral lesions, regardless of the age of the patient. Chondral defects are effective when the joint space is not compromised. When the Tonnis classification is two or greater, treatment of chondral lesions should be considered ineffective.

  14. Transplantation of tissue engineering neural network and formation of neuronal relay into the transected rat spinal cord.

    Science.gov (United States)

    Lai, Bi-Qin; Che, Ming-Tian; Du, Bao-Ling; Zeng, Xiang; Ma, Yuan-Huan; Feng, Bo; Qiu, Xue-Chen; Zhang, Ke; Liu, Shu; Shen, Hui-Yong; Wu, Jin-Lang; Ling, Eng-Ang; Zeng, Yuan-Shan

    2016-12-01

    Severe spinal cord injury (SCI) causes loss of neural connectivity and permanent functional deficits. Re-establishment of new neuronal relay circuits after SCI is therefore of paramount importance. The present study tested our hypothesis if co-culture of neurotrophin-3 (NT-3) gene-modified Schwann cells (SCs, NT-3-SCs) and TrkC (NT-3 receptor) gene-modified neural stem cells (NSCs, TrkC-NSCs) in a gelatin sponge scaffold could construct a tissue engineering neural network for re-establishing an anatomical neuronal relay after rat spinal cord transection. Eight weeks after transplantation, the neural network created a favorable microenvironment for axonal regeneration and for survival and synaptogenesis of NSC-derived neurons. Biotin conjugates of cholera toxin B subunit (b-CTB, a transneuronal tracer) was injected into the crushed sciatic nerve to label spinal cord neurons. Remarkably, not only ascending and descending nerve fibers, but also propriospinal neurons, made contacts with b-CTB positive NSC-derived neurons. Moreover, b-CTB positive NSC-derived neurons extended their axons making contacts with the motor neurons located in areas caudal to the injury/graft site of spinal cord. Further study showed that NT-3/TrkC interactions activated the PI3K/AKT/mTOR pathway and PI3K/AKT/CREB pathway affecting synaptogenesis of NSC-derived neurons. Together, our findings suggest that NT-3-mediated TrkC signaling plays an essential role in constructing a tissue engineering neural network thus representing a promising avenue for effective exogenous neuronal relay-based treatment for SCI. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. New aspects of fenestrated vasculature and tissue dynamics in the sensory circumventricular organs of adult brains

    Directory of Open Access Journals (Sweden)

    Seiji eMiyata

    2015-10-01

    Full Text Available The blood–brain barrier (BBB generally consists of endothelial tight junction barriers that prevent the free entry of blood-derived substances, thereby maintaining the extracellular environment of the brain. However, the circumventricular organs (CVOs, which are located along the midlines of the brain ventricles, lack these endothelial barriers and have fenestrated capillaries; therefore, they have a number of essential functions, including the transduction of information between the blood circulation and brain. Previous studies have demonstrated the extensive contribution of the CVOs to body fluid and thermal homeostasis, energy balance, the chemoreception of blood-derived substances, and neuroinflammation. In this review, recent advances have been discussed in fenestrated capillary characterization and dynamic tissue reconstruction accompanied by angiogenesis and neurogliogenesis in the sensory CVOs of adult brains. The sensory CVOs, including the organum vasculosum of the lamina terminalis (OVLT, subfornical organ (SFO, and area postrema (AP, have size-selective and heterogeneous vascular permeabilities. Astrocyte-/tanycyte-like neural stem cells (NSCs sense blood- and cerebrospinal fluid-derived information through the transient receptor potential vanilloid 1, a mechanical/osmotic receptor, Toll-like receptor 4, a lipopolysaccharide receptor, and Nax, a Na-sensing Na channel. They also express tight junction proteins and densely and tightly surround mature neurons to protect them from blood-derived neurotoxic substances, indicating that the NSCs of the CVOs perform BBB functions while maintaining the capacity to differentiate into new neurons and glial cells. In addition to neurogliogenesis, the density of fenestrated capillaries is regulated by angiogenesis, which is accompanied by the active proliferation and sprouting of endothelial cells. Vascular endothelial growth factor (VEGF signaling may be involved in angiogenesis and

  16. Effects of formalin fixation on tissue optical properties of in-vitro brain samples

    Science.gov (United States)

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

    2015-03-01

    Application of light spectroscopy based techniques for the detection of cancers have emerged as a promising approach for tumor diagnostics. In-vivo or freshly excised samples are normally used for point spectroscopic studies. However, ethical issues related to in-vivo studies, rapid decay of surgically excised tissues and sample availability puts a limitation on in-vivo and in-vitro studies. There has been a few studies reported on the application of formalin fixed samples with good discrimination capability. Usually formalin fixation is performed to prevent degradation of tissues after surgical resection. Fixing tissues in formalin prevents cell death by forming cross-linkages with proteins. Previous investigations have revealed that washing tissues fixed in formalin using phosphate buffered saline is known to reduce the effects of formalin during spectroscopic measurements. But this could not be the case with reflectance measurements. Hemoglobin is a principal absorbing medium in biological tissues in the visible range. Formalin fixation causes hemoglobin to seep out from red blood cells. Also, there could be alterations in the refractive index of tissues when fixed in formalin. In this study, we propose to investigate the changes in tissue optical properties between freshly excised and formalin fixed brain tissues. The results indicate a complete change in the spectral profile in the visible range where hemoglobin has its maximum absorption peaks. The characteristic bands of oxy-hemoglobin at 540, 580 nm and deoxy-hemoglobin at 555 nm disappear in the case of samples fixed in formalin. In addition, an increased spectral intensity was observed for the wavelengths greater than 650 nm where scattering phenomena are presumed to dominate.

  17. DTI and PWI analysis of peri-enhancing tumoral brain tissue in patients treated for glioblastoma.

    Science.gov (United States)

    Stecco, Alessandro; Pisani, Carla; Quarta, Raffaella; Brambilla, Marco; Masini, Laura; Beldì, Debora; Zizzari, Sara; Fossaceca, Rita; Krengli, Marco; Carriero, Alessandro

    2011-04-01

    To analyse the role of MR diffusion-tensor imaging (DTI) and perfusion-weighted imaging (PWI) in characterising tumour boundaries in patients with glioblastoma multiforme. Seventeen patients with surgically treated WHO IV grade gliomas who were candidates for adjuvant chemo-radiotherapy were enrolled. Before (T0) and after radiation treatment (T1), they underwent DTI and PWI, and the apparent diffusion coefficient (ADC), fractional anisotropy (FA) and relative cerebral blood volume (rCBV) in the enhancing tumour, the hyperintense tissue adjacent to the enhancing tumour, and the normal-appearing white matter (NAWM) adjacent to the hyperintense areas were analysed. The enhancing tissue at T1 was retrospectively divided on the basis of whether or not it was also enhancing at T0. The controls were the corresponding contralateral areas, on which we normalized the rCBV values, calculating the rCBV ratio. In NAWM, we did not find any significant differences in FA, ADC or rCBV. In the hyperintense perilesional regions, FA was significantly lower and ADC significantly higher than in the unaffected contralateral tissue; there were no significant differences in the rCBV maps. The values of FA, ADC and rCBV in enhancing neoplastic tissue were all significantly different from those observed in the contralateral tissue. There was no significant difference in rCBV values between the areas enhancing at T0 and those not enhancing at T0 but enhancing at T1, which may indicate the neoplastic transformation of apparently normal brain tissue. DTI metrics identify ultrastructural changes in hyperintense perilesional areas, but these are not specific for neoplastic tissue. rCBV seemed to reflect an ultrastructural alteration that was not visible at T0, but became visible (as neoplastic progression) on conventional MR images at T1. These findings could help identify tissue at risk of tumour infiltration.

  18. Scattering of Sculpted Light in Intact Brain Tissue, with implications for Optogenetics

    Science.gov (United States)

    Favre-Bulle, Itia A.; Preece, Daryl; Nieminen, Timo A.; Heap, Lucy A.; Scott, Ethan K.; Rubinsztein-Dunlop, Halina

    2015-06-01

    Optogenetics uses light to control and observe the activity of neurons, often using a focused laser beam. As brain tissue is a scattering medium, beams are distorted and spread with propagation through neural tissue, and the beam’s degradation has important implications in optogenetic experiments. To address this, we present an analysis of scattering and loss of intensity of focused laser beams at different depths within the brains of zebrafish larvae. Our experimental set-up uses a 488 nm laser and a spatial light modulator to focus a diffraction-limited spot of light within the brain. We use a combination of experimental measurements of back-scattered light in live larvae and computational modelling of the scattering to determine the spatial distribution of light. Modelling is performed using the Monte Carlo method, supported by generalised Lorenz-Mie theory in the single-scattering approximation. Scattering in areas rich in cell bodies is compared to that of regions of neuropil to identify the distinct and dramatic contributions that cell nuclei make to scattering. We demonstrate the feasibility of illuminating individual neurons, even in nucleus-rich areas, at depths beyond 100 μm using a spatial light modulator in combination with a standard laser and microscope optics.

  19. Elemental composition of `normal` and Alzheimer brain tissue by INA and PIXE analyses

    Energy Technology Data Exchange (ETDEWEB)

    Stedman, J.D.; Spyrou, N.M.

    1997-03-01

    Instrumental methods based on the nuclear and atomic properties of the elements have been used for many years to determine elemental concentrations in a variety of materials for biomedical, industrial and environmental applications. These methods offer high sensitivity for accurate trace element measurements, suffer few interfering or competing effects. Present no blank problems and are convenient for both research and routine analyses. The present article describes the use of two trace element techniques. Firstly the use of activation of stable nuclei irradiated by neutrons in the core of a low power research reactor as a means of detection of elements through the resulting gamma-rays emitted. Secondly, the observations of the interactions of energetic ion beams with the material in order to identify elemental species. Over recent years there has been some interest in determining the elemental composition of `normal` and Alzheimer affected brain tissue, however literature findings are inconsistent. Possible reasons for discrepancies need to be identified for further progress to be made. Here, post-mortem tissue samples, provided by the Alzheimer`s Disease Brain Bank, Institute of Psychiatry, London, were taken from the frontal, occipital, parietal and temporal lobes of both hemispheres of brains from 13 `normal` and 19 Alzheimer subjects. The elemental composition of the samples was determined using the analytical techniques of INAA (instrumental neutron activation analysis), RBS (Rutherford back-scattering) and PIXE (particle induced x-ray emission). The principal findings are summarised here. (author).

  20. Brain Metastasis in Bone and Soft Tissue Cancers: A Review of Incidence, Interventions, and Outcomes

    Directory of Open Access Journals (Sweden)

    Faris Shweikeh

    2014-01-01

    Full Text Available Bone and soft tissue malignancies account for a small portion of brain metastases. In this review, we characterize their incidence, treatments, and prognosis. Most of the data in the literature is based on case reports and small case series. Less than 5% of brain metastases are from bone and soft tissue sarcomas, occurring most commonly in Ewing’s sarcoma, malignant fibrous tumors, and osteosarcoma. Mean interval from initial cancer diagnosis to brain metastasis is in the range of 20–30 months, with most being detected before 24 months (osteosarcoma, Ewing sarcoma, chordoma, angiosarcoma, and rhabdomyosarcoma, some at 24–36 months (malignant fibrous tumors, malignant peripheral nerve sheath tumors, and alveolar soft part sarcoma, and a few after 36 months (chondrosarcoma and liposarcoma. Overall mean survival ranges between 7 and 16 months, with the majority surviving < 12 months (Ewing’s sarcoma, liposarcoma, malignant fibrous tumors, malignant peripheral nerve sheath tumors, angiosarcoma and chordomas. Management is heterogeneous involving surgery, radiosurgery, radiotherapy, and chemotherapy. While a survival advantage may exist for those given aggressive treatment involving surgical resection, such patients tended to have a favorable preoperative performance status and minimal systemic disease.

  1. White matter lesion extension to automatic brain tissue segmentation on MRI.

    Science.gov (United States)

    de Boer, Renske; Vrooman, Henri A; van der Lijn, Fedde; Vernooij, Meike W; Ikram, M Arfan; van der Lugt, Aad; Breteler, Monique M B; Niessen, Wiro J

    2009-05-01

    A fully automated brain tissue segmentation method is optimized and extended with white matter lesion segmentation. Cerebrospinal fluid (CSF), gray matter (GM) and white matter (WM) are segmented by an atlas-based k-nearest neighbor classifier on multi-modal magnetic resonance imaging data. This classifier is trained by registering brain atlases to the subject. The resulting GM segmentation is used to automatically find a white matter lesion (WML) threshold in a fluid-attenuated inversion recovery scan. False positive lesions are removed by ensuring that the lesions are within the white matter. The method was visually validated on a set of 209 subjects. No segmentation errors were found in 98% of the brain tissue segmentations and 97% of the WML segmentations. A quantitative evaluation using manual segmentations was performed on a subset of 6 subjects for CSF, GM and WM segmentation and an additional 14 for the WML segmentations. The results indicated that the automatic segmentation accuracy is close to the interobserver variability of manual segmentations.

  2. Role of Soft-Tissue Heterogeneity in Computational Models of Deep Brain Stimulation.

    Science.gov (United States)

    Howell, Bryan; McIntyre, Cameron C

    Bioelectric field models of deep brain stimulation (DBS) are commonly utilized in research and industrial applications. However, the wide range of different representations used for the human head in these models may be responsible for substantial variance in the stimulation predictions. Determine the relative error of ignoring cerebral vasculature and soft-tissue heterogeneity outside of the brain in computational models of DBS. We used a detailed atlas of the human head, coupled to magnetic resonance imaging data, to construct a range of subthalamic DBS volume conductor models. We incrementally simplified the most detailed base model and quantified changes in the stimulation thresholds for direct activation of corticofugal axons. Ignoring cerebral vasculature altered predictions of stimulation thresholds by brain altered predictions between -44 % and 174%. Heterogeneity in the soft tissues of the head, if unaccounted for, introduces a degree of uncertainty in predicting electrical stimulation of neural elements that is not negligible and thereby warrants consideration in future modeling studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Unified model of brain tissue microstructure dynamically binds diffusion and osmosis with extracellular space geometry

    Science.gov (United States)

    Yousefnezhad, Mohsen; Fotouhi, Morteza; Vejdani, Kaveh; Kamali-Zare, Padideh

    2016-09-01

    We present a universal model of brain tissue microstructure that dynamically links osmosis and diffusion with geometrical parameters of brain extracellular space (ECS). Our model robustly describes and predicts the nonlinear time dependency of tortuosity (λ =√{D /D* } ) changes with very high precision in various media with uniform and nonuniform osmolarity distribution, as demonstrated by previously published experimental data (D = free diffusion coefficient, D* = effective diffusion coefficient). To construct this model, we first developed a multiscale technique for computationally effective modeling of osmolarity in the brain tissue. Osmolarity differences across cell membranes lead to changes in the ECS dynamics. The evolution of the underlying dynamics is then captured by a level set method. Subsequently, using a homogenization technique, we derived a coarse-grained model with parameters that are explicitly related to the geometry of cells and their associated ECS. Our modeling results in very accurate analytical approximation of tortuosity based on time, space, osmolarity differences across cell membranes, and water permeability of cell membranes. Our model provides a unique platform for studying ECS dynamics not only in physiologic conditions such as sleep-wake cycles and aging but also in pathologic conditions such as stroke, seizure, and neoplasia, as well as in predictive pharmacokinetic modeling such as predicting medication biodistribution and efficacy and novel biomolecule development and testing.

  4. Distribution of dearomatised white spirit in brain, blood, and fat tissue after repeated exposure of rats

    DEFF Research Database (Denmark)

    Lof, A.; Lam, Henrik Rye; Gullstrand, E.

    1999-01-01

    spirit was 1.5 and 5.6 mg/kg in blood; 7.1 and 17.1 mg/kg in brain; 432 and 1452 mg/kg in fat tissue at the exposure levels of 400 and 800 p.p.m., respectively. The concentrations of n-nonane, n-decane, n-undecane, and total white spirit in blood and brain were not affected by the duration of exposure......Petroleum products with low content of aromatics have been increasingly used during the past years. This study investigates tissue disposition of dearomatised white spirit. In addition, brain neurotransmitter concentrations were measured. Male rats were exposed by inhalation to 0, 400 (2.29 mg....../l), or 800 p.p.m. (4.58 mg/l) of dearomatised white spirit, 6 hr/day, 5 days/week up to 3 weeks. Five rats from each group were sacrificed immediately after the exposure for 1, 2, or 3 weeks and 2, 4, 6, or 24 hr after the end of 3 weeks' exposure. After 3 weeks of exposure the concentration of total white...

  5. Development and Validation of a Method for Alcohol Analysis in Brain Tissue by Headspace Gas Chromatography with Flame Ionization Detector

    OpenAIRE

    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 br...

  6. Development and Preclinical Application of an Immunocompetent Transplant Model of Basal Breast Cancer with Lung, Liver and Brain Metastases.

    Directory of Open Access Journals (Sweden)

    Olga Aprelikova

    Full Text Available Triple negative breast cancer (TNBC is an aggressive subtype of breast cancer that is associated with a poor prognosis and for which no targeted therapies currently exist. In order to improve preclinical testing for TNBC that relies primarily on using human xenografts in immunodeficient mice, we have developed a novel immunocompetent syngeneic murine tumor transplant model for basal-like triple-negative breast cancer. The C3(1/SV40-T/t-antigen (C3(1/Tag mouse mammary tumor model in the FVB/N background shares important similarities with human basal-like TNBC. However, these tumors or derived cell lines are rejected when transplanted into wt FVB/N mice, likely due to the expression of SV40 T-antigen. We have developed a sub-line of mice (designated REAR mice that carry only one copy of the C3(1/Tag-antigen transgene resulting from a spontaneous transgene rearrangement in the original founder line. Unlike the original C3(1/Tag mice, REAR mice do not develop mammary tumors or other phenotypes observed in the original C3(1/Tag transgenic mice. REAR mice are more immunologically tolerant to SV40 T-antigen driven tumors and cell lines in an FVB/N background (including prostate tumors from TRAMP mice, but are otherwise immunologically intact. This transplant model system offers the ability to synchronously implant the C3(1/Tag tumor-derived M6 cell line or individual C3(1/Tag tumors from various stages of tumor development into the mammary fat pads or tail veins of REAR mice. C3(1/Tag tumors or M6 cells implanted into the mammary fat pads spontaneously metastasize at a high frequency to the lung and liver. M6 cells injected by tail vein can form brain metastases. We demonstrate that irradiated M6 tumor cells or the same cells expressing GM-CSF can act as a vaccine to retard tumor growth of implanted tumor cells in the REAR model. Preclinical studies performed in animals with an intact immune system should more authentically replicate treatment

  7. Relationship between concentrations of lutein and StARD3 among pediatric and geriatric human brain tissue

    Science.gov (United States)

    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...

  8. Cerebral transplantation of encapsulated mesenchymal stem cells improves cellular pathology after experimental traumatic brain injury

    DEFF Research Database (Denmark)

    Heile, Anna M B; Wallrapp, Christine; Klinge, Petra M

    2009-01-01

    PURPOSE: "Naked" human mesenchymal stem cells (MSC) are neuro-protective in experimental brain injury (TBI). In a controlled cortical impact (CCI) rat model, we investigated whether encapsulated MSC (eMSC) act similarly, and whether efficacy is augmented using cells transfected to produce the neuro...

  9. A white matter lesion-filling approach to improve brain tissue volume measurements

    Directory of Open Access Journals (Sweden)

    Sergi Valverde

    2014-01-01

    Full Text Available Multiple sclerosis white matter (WM lesions can affect brain tissue volume measurements of voxel-wise segmentation methods if these lesions are included in the segmentation process. Several authors have presented different techniques to improve brain tissue volume estimations by filling WM lesions before segmentation with intensities similar to those of WM. Here, we propose a new method to refill WM lesions, where contrary to similar approaches, lesion voxel intensities are replaced by random values of a normal distribution generated from the mean WM signal intensity of each two-dimensional slice. We test the performance of our method by estimating the deviation in tissue volume between a set of 30 T1-w 1.5 T and 30 T1-w 3 T images of healthy subjects and the same images where: WM lesions have been previously registered and afterwards replaced their voxel intensities to those between gray matter (GM and WM tissue. Tissue volume is computed independently using FAST and SPM8. When compared with the state-of-the-art methods, on 1.5 T data our method yields the lowest deviation in WM between original and filled images, independently of the segmentation method used. It also performs the lowest differences in GM when FAST is used and equals to the best method when SPM8 is employed. On 3 T data, our method also outperforms the state-of-the-art methods when FAST is used while performs similar to the best method when SPM8 is used. The proposed technique is currently available to researchers as a stand-alone program and as an SPM extension.

  10. A white matter lesion-filling approach to improve brain tissue volume measurements.

    Science.gov (United States)

    Valverde, Sergi; Oliver, Arnau; Lladó, Xavier

    2014-01-01

    Multiple sclerosis white matter (WM) lesions can affect brain tissue volume measurements of voxel-wise segmentation methods if these lesions are included in the segmentation process. Several authors have presented different techniques to improve brain tissue volume estimations by filling WM lesions before segmentation with intensities similar to those of WM. Here, we propose a new method to refill WM lesions, where contrary to similar approaches, lesion voxel intensities are replaced by random values of a normal distribution generated from the mean WM signal intensity of each two-dimensional slice. We test the performance of our method by estimating the deviation in tissue volume between a set of 30 T1-w 1.5 T and 30 T1-w 3 T images of healthy subjects and the same images where: WM lesions have been previously registered and afterwards replaced their voxel intensities to those between gray matter (GM) and WM tissue. Tissue volume is computed independently using FAST and SPM8. When compared with the state-of-the-art methods, on 1.5 T data our method yields the lowest deviation in WM between original and filled images, independently of the segmentation method used. It also performs the lowest differences in GM when FAST is used and equals to the best method when SPM8 is employed. On 3 T data, our method also outperforms the state-of-the-art methods when FAST is used while performs similar to the best method when SPM8 is used. The proposed technique is currently available to researchers as a stand-alone program and as an SPM extension.

  11. Brain tissue characterisation by infrared imaging in a rat glioma model.

    Science.gov (United States)

    Amharref, Nadia; Beljebbar, Abdelilah; Dukic, Sylvain; Venteo, Lydie; Schneider, Laurence; Pluot, Michel; Vistelle, Richard; Manfait, Michel

    2006-07-01

    Pathological changes associated with the development of brain tumor were investigated by Fourier transform infrared microspectroscopy (FT-IRM) with high spatial resolution. Using multivariate statistical analysis and imaging, all normal brain structures were discriminated from tumor and surrounding tumor tissues. These structural changes were mainly related to qualitative and quantitative changes in lipids (tumors contain little fat) and were correlated to the degree of myelination, an important factor in several neurodegenerative disorders. Lipid concentration and composition may thus be used as spectroscopic markers to discriminate between healthy and tumor tissues. Additionally, we have identified one peculiar structure all around the tumor. This structure could be attributed to infiltrative events, such as peritumoral oedema observed during tumor development. Our results highlight the ability of FT-IRM to identify the molecular origin that gave rise to the specific changes between healthy and diseased states. Comparison between pseudo-FT-IRM maps and histological examinations (Luxol fast blue, Luxol fast blue-cresyl violet staining) showed the complementarities of both techniques for early detection of tissue abnormalities.

  12. Behcet brain tissue identified with increased levels of Si and Al

    Science.gov (United States)

    Aranyosiova, Monika; Kopani, Martin; Rychly, Boris; Jakubovsky, Jan; Velic, Dusan

    2008-12-01

    Behcet disease is a multi-system disorder with still uncertain chemical causality. Chemical composition of molecules and elements in a human brain tissue of Behcet diseased patient is of interest. Time-of-flight secondary ion mass spectrometry is used to provide complex composition in Behcet disease and control tissues. Determined organic compounds are represented by fragments of carbohydrates, phospholipids, amino acids, and peptides in both samples without any qualitative differences. Trace heavy elements as Fe, Zn, and Cu are identified in Behcet disease tissue with increased intensities by only an averaged factor of 2.2 in comparison to the control. The significant differences between the control and Behcet disease tissues are in the presence of Si and Al. These two elements have significantly higher intensities by an averaged factor of 10.0 in Behcet disease tissue. The origin of Al and Si occurrence and the chronology of their accumulation are not clear, moreover this observation supports a significance of chemical characterization in an early stage of disease.

  13. Monoaminergic uptake in synaptosomes prepared from frozen brain tissue samples of normal and narcoleptic canines.

    Science.gov (United States)

    Valtier, D; Dement, W C; Mignot, E

    1992-08-14

    Canine narcolepsy, a model of the human disorder, is associated with altered catecholamine but not serotonin (5-HT) metabolism in some brain areas, particularly the amygdala. A possible explanation for these global changes could be the existence of specific defects in monoamine uptake processes. We have studied the uptake of [3H]norepinephrine (NE), [3H]dopamine (DA) and [3H]5-HT in synaptosomes prepared from cortex and amygdala of narcoleptic and control Doberman pinscher brains. Since narcoleptic canines are relatively few in number, we have used a specific brain freezing procedure that has been reported to allow restoration of metabolically functional tissue upon thawing. Preliminary studies comparing monoamine uptake in fresh and frozen brain samples of both groups of dogs were carried out and demonstrated that this procedure significantly altered serotoninergic but not noradrenergic and dopaminergic uptake. All further investigations were then done on synaptosomes prepared from frozen samples. Our results demonstrate that synaptosomal uptake of [3H]NE, [3H]DA and [3H]5-HT in cortex and amygdala are not altered in narcolepsy.

  14. Multifrequency magnetic resonance elastography of the brain reveals tissue degeneration in neuromyelitis optica spectrum disorder

    Energy Technology Data Exchange (ETDEWEB)

    Streitberger, Kaspar-Josche [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Fehlner, Andreas; Sack, Ingolf [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Pache, Florence [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Lacheta, Anna; Papazoglou, Sebastian; Brandt, Alexander [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Bellmann-Strobl, Judith [Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Ruprecht, Klemens [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Braun, Juergen [Charite - Universitaetsmedizin Berlin, Institute of Medical Informatics, Berlin (Germany); Paul, Friedemann [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Wuerfel, Jens [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Medical Image Analysis Center (MIAC AG), Basel (Switzerland)

    2017-05-15

    Application of multifrequency magnetic resonance elastography (MMRE) of the brain parenchyma in patients with neuromyelitis optica spectrum disorder (NMOSD) compared to age matched healthy controls (HC). 15 NMOSD patients and 17 age- and gender-matched HC were examined using MMRE. Two three-dimensional viscoelastic parameter maps, the magnitude G* and phase angle φ of the complex shear modulus were reconstructed by simultaneous inversion of full wave-field data in 1.9-mm isotropic resolution at 7 harmonic drive frequencies from 30 to 60 Hz. In NMOSD patients, a significant reduction of G* was observed within the white matter fraction (p = 0.017), predominantly within the thalamic regions (p = 0.003), compared to HC. These parameters exceeded the reduction in brain volume measured in patients versus HC (p = 0.02 whole-brain volume reduction). Volumetric differences in white matter fraction and the thalami were not detectable between patients and HC. However, phase angle φ was decreased in patients within the white matter (p = 0.03) and both thalamic regions (p = 0.044). MMRE reveals global tissue degeneration with accelerated softening of the brain parenchyma in patients with NMOSD. The predominant reduction of stiffness is found within the thalamic region and related white matter tracts, presumably reflecting Wallerian degeneration. (orig.)

  15. Transplantation of a Scaffold-Free Cartilage Tissue Analogue for the Treatment of Physeal Cartilage Injury of the Proximal Tibia in Rabbits.

    Science.gov (United States)

    Lee, Sang Uk; Lee, Jae Young; Joo, Sun Young; Lee, Yong Suk; Jeong, Changhoon

    2016-03-01

    The purpose of this study was to investigate the effects of transplantation of an in vitro-generated, scaffold-free, tissue-engineered cartilage tissue analogue (CTA) using a suspension chondrocyte culture in a rabbit growth-arrest model. We harvested cartilage cells from the articular cartilage of the joints of white rabbits and made a CTA using a suspension culture of 2×10⁷ cells/mL. An animal growth plate defect model was made on the medial side of the proximal tibial growth plate of both tibias of 6-week-old New Zealand white rabbits (n=10). The allogenic CTA was then transplanted onto the right proximal tibial defect. As a control, no implantation was performed on the left-side defect. Plain radiographs and the medial proximal tibial angle were obtained at 1-week intervals for evaluation of bone bridge formation and the degree of angular deformity until postoperative week 6. We performed a histological evaluation using hematoxylin-eosin and Alcian blue staining at postoperative weeks 4 and 6. Radiologic study revealed a median medial proximal tibial angle of 59.0° in the control group and 80.0° in the CTA group at 6 weeks. In the control group, statistically significant angular deformities were seen 3 weeks after transplantation (phistological examination, the transplanted CTA was maintained in the CTA group at 4 and 6 weeks postoperative. Bone bridge formation was observed in the control group. In this study, CTA transplantation minimized deformity in the rabbit growth plate injury model, probably via the attenuation of bone bridge formation.

  16. Retinal tissue transplantation and retinal progenitor cells: A therapeutic promise for patients with retinal disease Trasplante de tejido retiniano y de células progenitoras retinianas: una promesa terapéutica para pacientes con enfermedad de la retina

    National Research Council Canada - National Science Library

    Diana Estefania Jiménez

    2010-01-01

    .... Despite the lack of enough trials demonstrating positive functional results on eyesight recovery, the use of stem cells, retinal progenitor cells, and fetal retinal tissue transplantation seem very promising...

  17. An international comparison of the effect of policy shifts to organ donation following cardiocirculatory death (DCD on donation rates after brain death (DBD and transplantation rates.

    Directory of Open Access Journals (Sweden)

    Aric Bendorf

    Full Text Available During the past decade an increasing number of countries have adopted policies that emphasize donation after cardiocirculatory death (DCD in an attempt to address the widening gap between the demand for transplantable organs and the availability of organs from donation after brain death (DBD donors. In order to examine how these policy shifts have affected overall deceased organ donor (DD and DBD rates, we analyzed deceased donation rates from 82 countries from 2000-2010. On average, overall DD, DBD and DCD rates have increased over time, with the proportion of DCD increasing 0.3% per year (p = 0.01. Countries with higher DCD rates have, on average, lower DBD rates. For every one-per million population (pmp increase in the DCD rate, the average DBD rate decreased by 1.02 pmp (95% CI: 0.73, 1.32; p<0.0001. We also found that the number of organs transplanted per donor was significantly lower in DCD when compared to DBD donors with 1.51 less transplants per DCD compared to DBD (95% CI: 1.23, 1.79; p<0.001. Whilst the results do not infer a causal relationship between increased DCD and decreased DBD rates, the significant correlation between higher DCD and lower DBD rates coupled with the reduced number of organs transplanted per DCD donor suggests that a national policy focus on DCD may lead to an overall reduction in the number of transplants performed.

  18. Solid organ donation and transplantation.

    Science.gov (United States)

    Furlow, Bryant

    2012-01-01

    Medical imaging plays a key role in solid organ donation and transplantation. In addition to confirming the clinical diagnosis of brain death, imaging examinations are used to assess potential organ donors and recipients, evaluate donated organs, and monitor transplantation outcomes. This article introduces the history, biology, ethics, and institutions of organ donation and transplantation medicine. The article also discusses current and emerging imaging applications in the transplantation field and the controversial role of neuroimaging to confirm clinically diagnosed brain death.

  19. Astrocyte cultures derived from human brain tissue express angiotensinogen mRNA

    Energy Technology Data Exchange (ETDEWEB)

    Milsted, A.; Barna, B.P.; Ransohoff, R.M.; Brosnihan, K.B.; Ferrario, C.M. (Cleveland Clinic Foundation, OH (USA))

    1990-08-01

    The authors have identified human cultured cell lines that are useful for studying angiotensinogen gene expression and its regulation in the central nervous system. A model cell system of human central nervous system origin expressing angiotensinogen has not previously been available. Expression of angiotensinogen mRNA appears to be a basal property of noninduced human astrocytes, since astrocytic cell lines derived from human glioblastomas or nonneoplastic human brain tissue invariably produced angiotensinogen mRNA. In situ hybridization histochemistry revealed that angiotensinogen mRNA production was not limited to a subpopulation of astrocytes because >99% of cells in these cultures contained angiotensinogen mRNA. These cell lines will be useful in studies of the molecular mechanisms controlling angiotensin synthesis and the role of biologically active angiotensin in the human brain by allowing the authors to examine regulation of expression of the renin-angiotensin system in human astrocyte cultures.

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

    Science.gov (United States)

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

    2018-01-03

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

  1. IMPROVED HYBRID SEGMENTATION OF BRAIN MRI TISSUE AND TUMOR USING STATISTICAL FEATURES

    Directory of Open Access Journals (Sweden)

    S. Allin Christe

    2010-08-01

    Full Text Available Medical image segmentation is the most essential and crucial process in order to facilitate the characterization and visualization of the structure of interest in medical images. Relevant application in neuroradiology is the segmentation of MRI data sets of the human brain into the structure classes gray matter, white matter and cerebrospinal fluid (CSF and tumor. In this paper, brain image segmentation algorithms such as Fuzzy C means (FCM segmentation and Kohonen means(K means segmentation were implemented. In addition to this, new hybrid segmentation technique, namely, Fuzzy Kohonen means of image segmentation based on statistical feature clustering is proposed and implemented along with standard pixel value clustering method. The clustered segmented tissue images are compared with the Ground truth and its performance metric is also found. It is found that the feature based hybrid segmentation gives improved performance metric and improved classification accuracy rather than pixel based segmentation.

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

    Science.gov (United States)

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

    2017-01-01

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

  3. Growth trajectories of the human fetal brain tissues estimated from 3D reconstructed in utero MRI.

    Science.gov (United States)

    Scott, Julia A; Habas, Piotr A; Kim, Kio; Rajagopalan, Vidya; Hamzelou, Kia S; Corbett-Detig, James M; Barkovich, A James; Glenn, Orit A; Studholme, Colin

    2011-08-01

    In the latter half of gestation (20-40 gestational weeks), human brain growth accelerates in conjunction with cortical folding and the deceleration of ventricular zone progenitor cell proliferation. These processes are reflected in changes in the volume of respective fetal tissue zones. Thus far, growth trajectories of the fetal tissue zones have been extracted primarily from 2D measurements on histological sections and magnetic resonance imaging (MRI). In this study, the volumes of major fetal zones-cortical plate (CP), subplate and intermediate zone (SP+IZ), germinal matrix (GMAT), deep gray nuclei (DG), and ventricles (VENT)--are calculated from automatic segmentation of motion-corrected, 3D reconstructed MRI. We analyzed 48 T2-weighted MRI scans from 39 normally developing fetuses in utero between 20.57 and 31.14 gestational weeks (GW). The supratentorial volume (STV) increased linearly at a rate of 15.22% per week. The SP+IZ (14.75% per week) and DG (15.56% per week) volumes increased at similar rates. The CP increased at a greater relative rate (18.00% per week), while the VENT (9.18% per week) changed more slowly. Therefore, CP increased as a fraction of STV and the VENT fraction declined. The total GMAT volume slightly increased then decreased after 25 GW. We did not detect volumetric sexual dimorphisms or total hemispheric volume asymmetries, which may emerge later in gestation. Further application of the automated fetal brain segmentation to later gestational ages will bridge the gap between volumetric studies of premature brain development and normal brain development in utero. Published by Elsevier Ltd.

  4. Controlled single bubble cavitation collapse results in jet-induced injury in brain tissue.

    Science.gov (United States)

    Canchi, Saranya; Kelly, Karen; Hong, Yu; King, Michael A; Subhash, Ghatu; Sarntinoranont, Malisa

    2017-10-01

    Multiscale damage due to cavitation is considered as a potential mechanism of traumatic brain injury (TBI) associated with explosion. In this study, we employed a TBI relevant hippocampal ex vivo slice model to induce bubble cavitation. Placement of single reproducible seed bubbles allowed control of size, number, and tissue location to visualize and measure deformation parameters. Maximum strain value was measured at 45 µs after bubble collapse, presented with a distinct contour and coincided temporally and spatially with the liquid jet. Composite injury maps combined this maximum strain value with maximum measured bubble size and location along with histological injury patterns. This facilitated the correlation of bubble location and subsequent jet direction to the corresponding regions of high strain which overlapped with regions of observed injury. A dynamic threshold strain range for tearing of cerebral cortex was estimated to be between 0.5 and 0.6. For a seed bubble placed underneath the hippocampus, cavitation induced damage was observed in hippocampus (local), proximal cerebral cortex (marginal) and the midbrain/forebrain (remote) upon histological evaluation. Within this test model, zone of cavitation injury was greater than the maximum radius of the bubble. Separation of apposed structures, tissue tearing, and disruption of cellular layers defined early injury patterns that were not detected in the blast-exposed half of the brain slice. Ultrastructural pathology of the neurons exposed to cavitation was characterized by disintegration of plasma membrane along with loss of cellular content. The developed test system provided a controlled experimental platform to study cavitation induced high strain deformations on brain tissue slice. The goal of the future studies will be to lower underpressure magnitude and cavitation bubble size for more sensitive evaluation of injury. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Recusa de doação de órgãos e tecidos para transplante relatados por familiares de potenciais doadores Negación de donación de órganos y tejidos para transplante relatados por familiares de potenciales donadores Reasons for the family members' refusal to donate organ and tissue for transplant

    Directory of Open Access Journals (Sweden)

    Edvaldo Leal de Moraes

    2009-01-01

    Full Text Available OBJETIVO: Conhecer a percepção de familiares de potenciais doadores sobre os motivos de recusa para doação de órgãos e tecidos para transplante. MÉTODOS: Trata-se de uma pesquisa qualitativa, na vertente fenomenológica, modalidade "estrutura do fenômeno situado". Participaram do estudo oito familiares que recusaram a doação dos órgãos e tecidos. RESULTADOS: Após análise das entrevistas, foram revelados dez motivos de recusa, considerados pelos familiares. CONSIDERAÇÕES FINAIS: As proposições que emergiram revelaram que os motivos de recusa familiar para doação de órgãos e tecidos estão relacionados à crença, valores e inadequações no processo de doação e transplante.OBJETIVO: Conocer la percepción de familiares de potenciales donadores sobre los motivos de su negación para la donación de órganos y tejidos para transplante. MÉTODOS: Se trata de una investigación cualitativa, en la vertiente fenomenológica, modalidad "estructura del fenómeno situado". Participaron del estudio ocho familiares que se negaron a la donación de órganos y tejidos. RESULTADOS: Después del análisis de las entrevistas se revelaron diez motivos de negación expuestos por los familiares. CONSIDERACIONES FINALES: Las proposiciones que emergieron revelaron que los motivos de la negativa familiar para la donación de órganos y tejidos están relacionados a la creencia, valores e inadecuaciones en el proceso de donación y transplante.OBJECTIVE: To understand the perception of family members of potential donors in regard to their reasons for refusal to donate organ and tissue for transplant. METHODS: A qualitative phenomenological approach was used to conduct this study. A sample of eight family members who refused to donate organ and tissue for transplant participated in the study. RESULTS: Participants reported ten reasons for refusal to donate organ and tissue for transplant. FINAL CONSIDERATIONS: Reasons for the family members

  6. Immobilization of FLAG-Tagged Recombinant Adeno-Associated Virus 2 onto Tissue Engineering Scaffolds for the Improvement of Transgene Delivery in Cell Transplants.

    Science.gov (United States)

    Li, Hua; Zhang, Feng-Lan; Shi, Wen-Jie; Bai, Xue-Jia; Jia, Shu-Qin; Zhang, Chen-Guang; Ding, Wei

    2015-01-01

    The technology of virus-based genetic modification in tissue engineering has provided the opportunity to produce more flexible and versatile biomaterials for transplantation. Localizing the transgene expression with increased efficiency is critical for tissue engineering as well as a challenge for virus-based gene delivery. In this study, we tagged the VP2 protein of type 2 adeno-associated virus (AAV) with a 3×FLAG plasmid at the N-terminus and packaged a FLAG-tagged recombinant AAV2 chimeric mutant. The mutant AAVs were immobilized onto the tissue engineering scaffolds with crosslinked anti-FLAG antibodies by N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP). Cultured cells were seeded to scaffolds to form 3D transplants, and then tested for viral transduction both in vitro and in vivo. The results showed that our FLAG-tagged AAV2 exerted similar transduction efficiency compared with the wild type AAV2 when infected cultured cells. Following immobilization onto the scaffolds of PLGA or gelatin sponge with anti-FLAG antibodies, the viral mediated transgene expression was significantly improved and more localized. Our data demonstrated that the mutation of AAV capsid targeted for antibody-based immobilization could be a practical approach for more efficient and precise transgene delivery. It was also suggested that the immobilization of AAV might have attractive potentials in applications of tissue engineering involving the targeted gene manipulation in 3D tissue cultures.

  7. Immobilization of FLAG-Tagged Recombinant Adeno-Associated Virus 2 onto Tissue Engineering Scaffolds for the Improvement of Transgene Delivery in Cell Transplants.

    Directory of Open Access Journals (Sweden)

    Hua Li

    Full Text Available The technology of virus-based genetic modification in tissue engineering has provided the opportunity to produce more flexible and versatile biomaterials for transplantation. Localizing the transgene expression with increased efficiency is critical for tissue engineering as well as a challenge for virus-based gene delivery. In this study, we tagged the VP2 protein of type 2 adeno-associated virus (AAV with a 3×FLAG plasmid at the N-terminus and packaged a FLAG-tagged recombinant AAV2 chimeric mutant. The mutant AAVs were immobilized onto the tissue engineering scaffolds with crosslinked anti-FLAG antibodies by N-succinimidyl-3-(2-pyridyldithiol propionate (SPDP. Cultured cells were seeded to scaffolds to form 3D transplants, and then tested for viral transduction both in vitro and in vivo. The results showed that our FLAG-tagged AAV2 exerted similar transduction efficiency compared with the wild type AAV2 when infected cultured cells. Following immobilization onto the scaffolds of PLGA or gelatin sponge with anti-FLAG antibodies, the viral mediated transgene expression was significantly improved and more localized. Our data demonstrated that the mutation of AAV capsid targeted for antibody-based immobilization could be a practical approach for more efficient and precise transgene delivery. It was also suggested that the immobilization of AAV might have attractive potentials in applications of tissue engineering involving the targeted gene manipulation in 3D tissue cultures.

  8. Experimental study on the toxicity of povidone-iodine solution in brain tissues of rabbits

    OpenAIRE

    Li, Shu-Hua; Wang, Yu; Gao, Hai-Bin; Zhao, Kun; Hou, Yu-Chen; Sun, Wei

    2015-01-01

    Objective: To determine whether Povidone-iodine was toxic to brain tissues by rinsing the cerebral cortex of New Zealand rabbits with Povidone-iodine Solution of different concentrations. Methods: 12 New Zealand rabbits were randomly divided into 4 groups (Group A, B, C and D, 3 rabbits each group). In each group, the left cerebral cortex of rabbits was rinsed with physiological saline after the craniotomy; in Group A and B, the right cerebral cortex of rabbits was also locally rinsed with Po...

  9. Pediatric brain tumors of neuroepithelial tissue; Hirntumoren des neuroepithelialen Gewebes im Kindesalter

    Energy Technology Data Exchange (ETDEWEB)

    Papanagiotou, P.; Politi, M. [Klinikum Bremen-Mitte/Bremen-Ost, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Bremen (Germany); Bergmann, M. [Klinikum Bremen-Mitte, Institut fuer Klinische Neuropathologie, Bremen (Germany); Pekrun, A. [Klinikum Bremen-Mitte, Klinik fuer Kinder- und Jugendmedizin, paed. Haematologie/Onkologie, Neonatologie, Bremen (Germany); Juergens, K.U. [Klinikum Bremen-Mitte, ZEMODI-Zentrum fuer moderne Diagnostik, MRT, Nuklearmedizin und PET-CT, Bremen (Germany)

    2014-08-15

    Tumors of neuroepithelial tissue represent the largest group of pediatric brain tumors by far and has therefore been divided into several discrete tumor subtypes each corresponding to a specific component of the neuropil. The neuropil contains several subtypes of glial cells, including astrocytes, oligodendrocytes, ependymal cells and modified ependymal cells that form the choroid plexus. This review discusses the imaging aspects of the most common pediatric tumors of neuroepithelial tissue. (orig.) [German] Tumoren des neuroepithelialen Gewebes stellen die mit Abstand groesste Gruppe der paediatrischen Hirntumoren dar und werden je nach deren Ursprung in diversen Subtypen unterteilt. Das Neuropil beinhaltet diverse Subtypen von Gliazellen: Astrozyten, Oligodendrozyten, ependymale Zellen und modifizierte ependymale Zellen, die den Plexus choroideus formen. In diesem Review werden die bildgebenden Aspekte mittels CT und MRT der haeufigsten Tumoren des neuroepithelialen Gewebes diskutiert. (orig.)

  10. Rat adipose tissue-derived stem cells transplantation attenuates cardiac dysfunction post infarction and biopolymers enhance cell retention.

    Directory of Open Access Journals (Sweden)

    Maria E Danoviz

    Full Text Available BACKGROUND: Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI. METHODOLOGY/PRINCIPAL FINDINGS: 99mTc-labeled ASCs (1x10(6 cells isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C, or culture medium (ASC/M as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively. Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT and control groups (culture medium, fibrin, or collagen alone. Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW, a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. CONCLUSIONS: We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administering co-injection of ASCs with biopolymers.

  11. Use of flow cytometry for high-throughput cell population estimates in fixed brain tissue

    Directory of Open Access Journals (Sweden)

    Nicole A Young

    2012-07-01

    Full Text Available The numbers and types of cells in an area of cortex define its function. Therefore it is essential to characterize the numbers and distributions of total cells in areas of the cortex, as well as to identify numbers of subclasses of neurons and glial cells. To date, the large size of the primate brain and the lack of innovation in cell counting methods have been a roadblock to obtaining high-resolution maps of cell and neuron density across the cortex in humans and non-human primates. Stereological counting methods and the isotropic fractionator are valuable tools for estimating cell numbers, but are better suited to smaller, well-defined brain structures or to cortex as a whole. In the present study, we have extended our flow-cytometry based counting method, the flow fractionator (Collins et al., 2010a, to include high-throughput total cell population estimates in homogenized cortical samples. We demonstrate that our method produces consistent, accurate and repeatable cell estimates quickly. The estimates we report are in excellent agreement with estimates for the same samples obtained using a Neubauer chamber and a fluorescence microscope. We show that our flow cytometry-based method for total cell estimation in homogenized brain tissue is more efficient and more precise than manual counting methods. The addition of automated nuclei counting to our flow fractionator method allows for a fully automated, rapid characterization of total cells and neuronal and non-neuronal populations in human and non-human primate brains, providing valuable data to further our understanding of the functional organization of normal, aging and diseased brains.

  12. Quantifying brain tissue volume in multiple sclerosis with automated lesion segmentation and filling

    Directory of Open Access Journals (Sweden)

    Sergi Valverde

    2015-01-01

    Full Text Available Lesion filling has been successfully applied to reduce the effect of hypo-intense T1-w Multiple Sclerosis (MS lesions on automatic brain tissue segmentation. However, a study of fully automated pipelines incorporating lesion segmentation and lesion filling on tissue volume analysis has not yet been performed. Here, we analyzed the % of error introduced by automating the lesion segmentation and filling processes in the tissue segmentation of 70 clinically isolated syndrome patient images. First of all, images were processed using the LST and SLS toolkits with different pipeline combinations that differed in either automated or manual lesion segmentation, and lesion filling or masking out lesions. Then, images processed following each of the pipelines were segmented into gray matter (GM and white matter (WM using SPM8, and compared with the same images where expert lesion annotations were filled before segmentation. Our results showed that fully automated lesion segmentation and filling pipelines reduced significantly the % of error in GM and WM volume on images of MS patients, and performed similarly to the images where expert lesion annotations were masked before segmentation. In all the pipelines, the amount of misclassified lesion voxels was the main cause in the observed error in GM and WM volume. However, the % of error was significantly lower when automatically estimated lesions were filled and not masked before segmentation. These results are relevant and suggest that LST and SLS toolboxes allow the performance of accurate brain tissue volume measurements without any kind of manual intervention, which can be convenient not only in terms of time and economic costs, but also to avoid the inherent intra/inter variability between manual annotations.

  13. Quantifying brain tissue volume in multiple sclerosis with automated lesion segmentation and filling.

    Science.gov (United States)

    Valverde, Sergi; Oliver, Arnau; Roura, Eloy; Pareto, Deborah; Vilanova, Joan C; Ramió-Torrentà, Lluís; Sastre-Garriga, Jaume; Montalban, Xavier; Rovira, Àlex; Lladó, Xavier

    2015-01-01

    Lesion filling has been successfully applied to reduce the effect of hypo-intense T1-w Multiple Sclerosis (MS) lesions on automatic brain tissue segmentation. However, a study of fully automated pipelines incorporating lesion segmentation and lesion filling on tissue volume analysis has not yet been performed. Here, we analyzed the % of error introduced by automating the lesion segmentation and filling processes in the tissue segmentation of 70 clinically isolated syndrome patient images. First of all, images were processed using the LST and SLS toolkits with different pipeline combinations that differed in either automated or manual lesion segmentation, and lesion filling or masking out lesions. Then, images processed following each of the pipelines were segmented into gray matter (GM) and white matter (WM) using SPM8, and compared with the same images where expert lesion annotations were filled before segmentation. Our results showed that fully automated lesion segmentation and filling pipelines reduced significantly the % of error in GM and WM volume on images of MS patients, and performed similarly to the images where expert lesion annotations were masked before segmentation. In all the pipelines, the amount of misclassified lesion voxels was the main cause in the observed error in GM and WM volume. However, the % of error was significantly lower when automatically estimated lesions were filled and not masked before segmentation. These results are relevant and suggest that LST and SLS toolboxes allow the performance of accurate brain tissue volume measurements without any kind of manual intervention, which can be convenient not only in terms of time and economic costs, but also to avoid the inherent intra/inter variability between manual annotations.

  14. Dynamic, mating-induced gene expression changes in female head and brain tissues of Drosophila melanogaster

    Science.gov (United States)

    2010-01-01

    Background Drosophila melanogaster females show changes in behavior and physiology after mating that are thought to maximize the number of progeny resulting from the most recent copulation. Sperm and seminal fluid proteins induce post-mating changes in females, however, very little is known about the resulting gene expression changes in female head and central nervous system tissues that contribute to the post-mating response. Results We determined the temporal gene expression changes in female head tissues 0-2, 24, 48 and 72 hours after mating. Females from each time point had a unique post-mating gene expression response, with 72 hours post-mating having the largest number of genes with significant changes in expression. At most time points, genes expressed in the head fat body that encode products involved in metabolism showed a marked change in expression. Additional analysis of gene expression changes in dissected brain tissues 24 hours post-mating revealed changes in transcript abundance of many genes, notably, the reduced transcript abundance of genes that encode ion channels. Conclusions Substantial changes occur in the regulation of many genes in female head tissues after mating, which might underlie aspects of the female post-mating response. These results provide new insights into the physiological and metabolic changes that accompany changes in female behaviors. PMID:20925960

  15. Dynamic, mating-induced gene expression changes in female head and brain tissues of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Stirling Emma J

    2010-10-01

    Full Text Available Abstract Background Drosophila melanogaster females show changes in behavior and physiology after mating that are thought to maximize the number of progeny resulting from the most recent copulation. Sperm and seminal fluid proteins induce post-mating changes in females, however, very little is known about the resulting gene expression changes in female head and central nervous system tissues that contribute to the post-mating response. Results We determined the temporal gene expression changes in female head tissues 0-2, 24, 48 and 72 hours after mating. Females from each time point had a unique post-mating gene expression response, with 72 hours post-mating having the largest number of genes with significant changes in expression. At most time points, genes expressed in the head fat body that encode products involved in metabolism showed a marked change in expression. Additional analysis of gene expression changes in dissected brain tissues 24 hours post-mating revealed changes in transcript abundance of many genes, notably, the reduced transcript abundance of genes that encode ion channels. Conclusions Substantial changes occur in the regulation of many genes in female head tissues after mating, which might underlie aspects of the female post-mating response. These results provide new insights into the physiological and metabolic changes that accompany changes in female behaviors.

  16. Predictive factors of brain death in severe stroke patients identified by organ procurement and transplant coordination in Lorrain, France.

    Science.gov (United States)

    Humbertjean, Lisa; Mione, Gioia; Fay, Renaud; Durin, Laurent; Planel, Sophie; Lacour, Jean-Christophe; Enea, Ana-Maria; Richard, Sébastien

    2016-03-01

    There are no established predictive factors to identify patients at the acute phase of severe stroke with a high probability of presenting brain death (BD). We retrospectively collected clinical and paraclinical data of consecutive patients at the acute phase of severe stroke with a potential progression to BD through the hospital organ procurement and transplant coordination system in five centres in Lorrain (France) between 1 January 2012 and 31 December 2013. Final endpoint was adjudicated BD. Of 400 included patients, 91 (23%) presented adjudicated BD. Initial Glasgow Coma Scale score ≤6 (P = 0.008), herniation (P = 0.009), hydrocephalus (P = 0.019), initial systolic blood pressure >150 mmHg (P = 0.002), past history of alcohol abuse (P = 0.019) and stroke volume >65 ml (P = 0.040) were significantly associated with BD progression. Two prognostic scores for stroke with unquantifiable or quantifiable volume were built according to the number of risk factors presented. Following internal validation, the respective bias-corrected predictive performance (c-index) of the two scores was 72% (95% confidence interval: 67-78%) and 77% (95% confidence interval: 72-82%). These scores could form the basis of a simple tool of six criteria to help physicians make the difficult decision of intensive care unit management to preserve organs in potential donors. © 2015 Steunstichting ESOT.

  17. Terahertz spectroscopy and detection of brain tumor in rat fresh-tissue samples

    Science.gov (United States)

    Yamaguchi, S.; Fukushi, Y.; Kubota, O.; Itsuji, T.; Yamamoto, S.; Ouchi, T.

    2015-03-01

    Terahertz (THz) spectroscopy and imaging of biomedical samples is expected to be an important application of THz analysis techniques. Identification and localization of tumor tissue, imaging of biological samples, and analysis of DNA by THz spectroscopy have been reported. THz time-domain spectroscopy (TDS) is useful for obtaining the refractive index over a broad frequency range. However, THz-TDS spectra of fresh tissue samples are sensitive to procedures such as sample preparation, and a standardized measurement protocol is required. Therefore, in this work, we establish a protocol for measurements of THz spectra of fresh tissue and demonstrate reliable detection of rat brain tumor tissue. We use a reflection THz-TDS system to measure the refractive index spectra of the samples mounted on a quartz plate. The tissue samples were measured immediately after sectioning to avoid sample denaturalization during storage. Special care was taken in THz data processing to eliminate parasitic reflections and reduce noise. The error level in our refractive index measurements was as low as 0.02 in the frequency range 0.8-1.5 THz. With increasing frequency, the refractive index in the tumor and normal regions monotonically decreased, similarly to water, and it was 0.02 higher in the tumor regions. The spectral data suggest that the tumor regions have higher water content. Hematoxylin-eosin stained images showed that increased cell density was also responsible for the observed spectral features. A set of samples from 10 rats showed consistent results. Our results suggest that reliable tumor detection in fresh tissue without pretreatment is possible with THz spectroscopy measurements. THz spectroscopy has the potential to become a real-time in vivo diagnostic method.

  18. Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain and liver tissues from psychiatric disorders: rethinking the brain?liver axis

    OpenAIRE

    Yang, B; Ren, Q; Zhang, J-c; Chen, Q-X; Hashimoto, K

    2017-01-01

    Brain-derived neurotrophic factor (BDNF) has a role in the pathophysiology of psychiatric disorders. The precursor proBDNF is converted to mature BDNF and BDNF pro-peptide, the N-terminal fragment of proBDNF; however, the precise function of these proteins in psychiatric disorders is unknown. We sought to determine whether expression of these proteins is altered in the brain and peripheral tissues from patients with psychiatric disorders. We measured protein expression of proBDNF, mature BDNF...

  19. Hydrogel-delivered brain-derived neurotrophic factor promotes tissue repair and recovery after stroke.

    Science.gov (United States)

    Cook, Douglas J; Nguyen, Cynthia; Chun, Hyun N; L Llorente, Irene; Chiu, Abraham S; Machnicki, Michal; Zarembinski, Thomas I; Carmichael, S Thomas

    2017-03-01

    Stroke is the leading cause of adult disability. Systemic delivery of candidate neural repair therapies is limited by the blood-brain barrier and off-target effects. We tested a bioengineering approach for local depot release of BDNF from the infarct cavity for neural repair in chronic periods after stroke. The brain release levels of a hyaluronic acid hydrogel + BDNF were tested in several stroke models in mouse (strains C57Bl/6, DBA) and non-human primate ( Macaca fascicularis) and tracked with MRI. The behavioral recovery effects of hydrogel + BDNF and the effects on tissue repair outcomes were determined. Hydrogel-delivered BDNF diffuses from the stroke cavity into peri-infarct tissue over 3 weeks in two mouse stroke models, compared with 1 week for direct BDNF injection. Hydrogel delivery of BDNF promotes recovery of motor function. Mapping of motor system connections indicates that hydrogel-BDNF induces axonal sprouting within existing cortical and cortico-striatal systems. Pharmacogenetic studies show that hydrogel-BDNF induces the initial migration of immature neurons into the peri-infarct cortex and their long-term survival. In chronic stroke in the non-human primate, hydrogel-released BDNF can be detected up to 2 cm from the infarct, a distance relevant to human functional recovery in stroke. The hydrogel can be tracked by MRI in mouse and primate.

  20. Hierarchical brain tissue segmentation and its application in multiple sclerosis and Alzheimer's disease

    Science.gov (United States)

    Lei, Tianhu; Udupa, Jayaram K.; Moonis, Gul; Schwartz, Eric; Balcer, Laura

    2005-04-01

    Based on Fuzzy Connectedness (FC) object delineation principles and algorithms, a hierarchical brain tissue segmentation technique has been developed for MR images. After MR image background intensity inhomogeneity correction and intensity standardization, three FC objects for cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM) are generated via FC object delineation, and an intracranial (IC) mask is created via morphological operations. Then, the IC mask is decomposed into parenchymal (BP) and CSF masks, while the BP mask is separated into WM and GM masks. WM mask is further divided into pure and dirty white matter masks (PWM and DWM). In Multiple Sclerosis studies, a severe white matter lesion (LS) mask is defined from DWM mask. Based on the segmented brain tissue images, a histogram-based method has been developed to find disease-specific, image-based quantitative markers for characterizing the macromolecular manifestation of the two diseases. These same procedures have been applied to 65 MS (46 patients and 19 normal subjects) and 25 AD (15 patients and 10 normal subjects) data sets, each of which consists of FSE PD- and T2-weighted MR images. Histograms representing standardized PD and T2 intensity distributions and their numerical parameters provide an effective means for characterizing the two diseases. The procedures are systematic, nearly automated, robust, and the results are reproducible.

  1. Characterisation of carbon paste electrodes for real-time amperometric monitoring of brain tissue oxygen.

    Science.gov (United States)

    Bolger, Fiachra B; McHugh, Stephen B; Bennett, Rachel; Li, Jennifer; Ishiwari, Keita; Francois, Jennifer; Conway, Michael W; Gilmour, Gary; Bannerman, David M; Fillenz, Marianne; Tricklebank, Mark; Lowry, John P

    2011-02-15

    Tissue O₂ can be monitored using a variety of electrochemical techniques and electrodes. In vitro and in vivo characterisation studies for O₂ reduction at carbon paste electrodes (CPEs) using constant potential amperometry (CPA) are presented. Cyclic voltammetry indicated that an applied potential of -650 mV is required for O₂ reduction at CPEs. High sensitivity (-1.49 ± 0.01 nA/μM), low detection limit (ca. 0.1 μM) and good linear response characteristics (R² > 0.99) were observed in calibration experiments performed at this potential. There was also no effect of pH, temperature, and ion changes, and no dependence upon flow/fluid convection (stirring). Several compounds (e.g. dopamine and its metabolites) present in brain extracellular fluid were tested at physiological concentrations and shown not to interfere with the CPA O₂ signal. In vivo experiments confirmed a sub-second response time observed in vitro and demonstrated long-term stability extending over twelve weeks, with minimal O₂ consumption (ca. 1 nmol/h). These results indicate that CPEs operating amperometrically at a constant potential of -650 mV (vs. SCE) can be used reliably to continuously monitor brain extracellular tissue O₂. © 2010 Elsevier B.V. All rights reserved.

  2. Study on Material Parameters Identification of Brain Tissue Considering Uncertainty of Friction Coefficient

    Science.gov (United States)

    Guan, Fengjiao; Zhang, Guanjun; Liu, Jie; Wang, Shujing; Luo, Xu; Zhu, Feng

    2017-10-01

    Accurate material parameters are critical to construct the high biofidelity finite element (FE) models. However, it is hard to obtain the brain tissue parameters accurately because of the effects of irregular geometry and uncertain boundary conditions. Considering the complexity of material test and the uncertainty of friction coefficient, a computational inverse method for viscoelastic material parameters identification of brain tissue is presented based on the interval analysis method. Firstly, the intervals are used to quantify the friction coefficient in the boundary condition. And then the inverse problem of material parameters identification under uncertain friction coefficient is transformed into two types of deterministic inverse problem. Finally the intelligent optimization algorithm is used to solve the two types of deterministic inverse problems quickly and accurately, and the range of material parameters can be easily acquired with no need of a variety of samples. The efficiency and convergence of this method are demonstrated by the material parameters identification of thalamus. The proposed method provides a potential effective tool for building high biofidelity human finite element model in the study of traffic accident injury.

  3. Significant effects of antiretroviral therapy on global gene expression in brain tissues of patients with HIV-1-associated neurocognitive disorders.

    Directory of Open Access Journals (Sweden)

    Alejandra Borjabad

    2011-09-01

    Full Text Available Antiretroviral therapy (ART has reduced morbidity and mortality in HIV-1 infection; however HIV-1-associated neurocognitive disorders (HAND persist despite treatment. The reasons for the limited efficacy of ART in the brain are unknown. Here we used functional genomics to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed genome-wide microarray analysis using Affymetrix U133 Plus 2.0 Arrays, real-time PCR, and immunohistochemistry in brain tissues from seven treated and eight untreated HAND patients and six uninfected controls. We also determined brain virus burdens by real-time PCR. Treated and untreated HAND brains had distinct gene expression profiles with ART transcriptomes clustering with HIV-1-negative controls. The molecular disease profile of untreated HAND showed dysregulated expression of 1470 genes at p<0.05, with activation of antiviral and immune responses and suppression of synaptic transmission and neurogenesis. The overall brain transcriptome changes in these patients were independent of histological manifestation of HIV-1 encephalitis and brain virus burdens. Depending on treatment compliance, brain transcriptomes from patients on ART had 83% to 93% fewer dysregulated genes and significantly lower dysregulation of biological pathways compared to untreated patients, with particular improvement indicated for nervous system functions. However a core of about 100 genes remained similarly dysregulated in both treated and untreated patient brain tissues. These genes participate in adaptive immune responses, and in interferon, cell cycle, and myelin pathways. Fluctuations of cellular gene expression in the brain correlated in Pearson's formula analysis with plasma but not brain virus burden. Our results define for the first time an aberrant genome-wide brain transcriptome of untreated HAND and they suggest that antiretroviral treatment can be broadly effective in reducing

  4. Detection of Neospora caninum-DNA in brain tissues from pigeons in Changchun, Jilin (China).

    Science.gov (United States)

    Du, Ling; Yang, Dongsheng; Zhai, Tao; Gong, Pengtao; Zhang, Xichen; Li, Jianhua

    2015-11-30

    Neospora caninum is an intracellular protozoan infecting many domestic and wild animals. The domestic chicken (Gallus domesticus) and the sparrow (Passer domesticus) are known as natural intermediate hosts of N. caninum, whereas the role of other birds such as pigeons is still unclear. In the present study, pigeon brain tissues collected in Jilin of China were screened by N. caninum specific-nested PCR to determine whether pigeons functioned as the natural intermediate hosts of N. caninum. The prevalences of N. caninum DNA and Toxoplasma gondii DNA among the brain samples were 30% (63/210) and 13.33% (28/210), respectively. One brain sample was co-infected with N. caninum and T. gondii in naturally infected pigeon. Of the 63 positive samples 42 could be assigned to the NC-PR genotype, 10 to the NC-1 genotypes and 5, 3 and 3 respectively to the each of the three new genotypes identified, indicating genetic polymorphism of N. caninum in pigeons in Jilin of China. The present study expanded the list of intermediate hosts of N. caninum to include pigeons which suggests that pigeons are involved in the transmission of the N. caninum. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. A novel approach to quantify different iron forms in ex-vivo human brain tissue

    Science.gov (United States)

    Kumar, Pravin; Bulk, Marjolein; Webb, Andrew; van der Weerd, Louise; Oosterkamp, Tjerk H.; Huber, Martina; Bossoni, Lucia

    2016-12-01

    We propose a novel combination of methods to study the physical properties of ferric ions and iron-oxide nanoparticles in post-mortem human brain, based on the combination of Electron Paramagnetic Resonance (EPR) and SQUID magnetometry. By means of EPR, we derive the concentration of the low molecular weight iron pool, as well as the product of its electron spin relaxation times. Additionally, by SQUID magnetometry we identify iron mineralization products ascribable to a magnetite/maghemite phase and a ferrihydrite (ferritin) phase. We further derive the concentration of magnetite/maghemite and of ferritin nanoparticles. To test out the new combined methodology, we studied brain tissue of an Alzheimer’s patient and a healthy control. Finally, we estimate that the size of the magnetite/maghemite nanoparticles, whose magnetic moments are blocked at room temperature, exceeds 40-50 nm, which is not compatible with the ferritin protein, the core of which is typically 6-8 nm. We believe that this methodology could be beneficial in the study of neurodegenerative diseases such as Alzheimer’s Disease which are characterized by abnormal iron accumulation in the brain.

  6. Brain-specific rescue of Clock reveals system-driven transcriptional rhythms in peripheral tissue.

    Science.gov (United States)

    Hughes, Michael E; Hong, Hee-Kyung; Chong, Jason L; Indacochea, Alejandra A; Lee, Samuel S; Han, Michael; Takahashi, Joseph S; Hogenesch, John B

    2012-01-01

    The circadian regulatory network is organized in a hierarchical fashion, with a central oscillator in the suprachiasmatic nuclei (SCN) orchestrating circadian oscillations in peripheral tissues. The nature of the relationship between central and peripheral oscillators, however, is poorly understood. We used the tetOFF expression system to specifically restore Clock function in the brains of Clock(Δ19) mice, which have compromised circadian clocks. Rescued mice showed normal locomotor rhythms in constant darkness, with activity period lengths approximating wildtype controls. We used microarray analysis to assess whether brain-specific rescue of circadian rhythmicity was sufficient to restore circadian transcriptional output in the liver. Compared to Clock mutants, Clock-rescue mice showed significantly larger numbers of cycling transcripts with appropriate phase and period lengths, including many components of the core circadian oscillator. This indicates that the SCN oscillator overcomes local circadian defects and signals directly to the molecular clock. Interestingly, the vast majority of core clock genes in liver were responsive to Clock expression in the SCN, suggesting that core clock genes in peripheral tissues are intrinsically sensitive to SCN cues. Nevertheless, most circadian output in the liver was absent or severely low-amplitude in Clock-rescue animals, demonstrating that the majority of peripheral transcriptional rhythms depend on a fully functional local circadian oscillator. We identified several new system-driven rhythmic genes in the liver, including Alas1 and Mfsd2. Finally, we show that 12-hour transcriptional rhythms (i.e., circadian "harmonics") are disrupted by Clock loss-of-function. Brain-specific rescue of Clock converted 12-hour rhythms into 24-hour rhythms, suggesting that signaling via the central circadian oscillator is required to generate one of the two daily peaks of expression. Based on these data, we conclude that 12-hour rhythms

  7. Brain-specific rescue of Clock reveals system-driven transcriptional rhythms in peripheral tissue.

    Directory of Open Access Journals (Sweden)

    Michael E Hughes

    Full Text Available The circadian regulatory network is organized in a hierarchical fashion, with a central oscillator in the suprachiasmatic nuclei (SCN orchestrating circadian oscillations in peripheral tissues. The nature of the relationship between central and peripheral oscillators, however, is poorly understood. We used the tetOFF expression system to specifically restore Clock function in the brains of Clock(Δ19 mice, which have compromised circadian clocks. Rescued mice showed normal locomotor rhythms in constant darkness, with activity period lengths approximating wildtype controls. We used microarray analysis to assess whether brain-specific rescue of circadian rhythmicity was sufficient to restore circadian transcriptional output in the liver. Compared to Clock mutants, Clock-rescue mice showed significantly larger numbers of cycling transcripts with appropriate phase and period lengths, including many components of the core circadian oscillator. This indicates that the SCN oscillator overcomes local circadian defects and signals directly to the molecular clock. Interestingly, the vast majority of core clock genes in liver were responsive to Clock expression in the SCN, suggesting that core clock genes in peripheral tissues are intrinsically sensitive to SCN cues. Nevertheless, most circadian output in the liver was absent or severely low-amplitude in Clock-rescue animals, demonstrating that the majority of peripheral transcriptional rhythms depend on a fully functional local circadian oscillator. We identified several new system-driven rhythmic genes in the liver, including Alas1 and Mfsd2. Finally, we show that 12-hour transcriptional rhythms (i.e., circadian "harmonics" are disrupted by Clock loss-of-function. Brain-specific rescue of Clock converted 12-hour rhythms into 24-hour rhythms, suggesting that signaling via the central circadian oscillator is required to generate one of the two daily peaks of expression. Based on these data, we conclude

  8. Cadaveric transplantation.

    Directory of Open Access Journals (Sweden)

    Gokal R

    1993-10-01

    Full Text Available Transplantation is already the optimum treatment for terminal renal failure. Donor organ shortage means that there are large number of patients on dialysis awaiting this treatment. This has in some countries led to unacceptable unscrupulous practices of live non-related graft donation. The outcome of graft and patient after transplantation has improved significantly based on a better understanding of immunopathology, immunosuppression and tissue typing. The future is promising and xenografting may well solve the organ shortage but undoubtedly will raise other issues.

  9. Fluoride Alteration of [3H]Glucose Uptake in Wistar Rat Brain and Peripheral Tissues.

    Science.gov (United States)

    Rogalska, Anna; Kuter, Katarzyna; Żelazko, Aleksandra; Głogowska-Gruszka, Anna; Świętochowska, Elżbieta; Nowak, Przemysław

    2017-04-01

    The present study was designed to investigate the role of postnatal fluoride intake on [3H]glucose uptake and transport in rat brain and peripheral tissues. Sodium fluoride (NaF) in a concentration of 10 or 50 ppm was added to the drinking water of adult Wistar rats. The control group received distilled water. After 4 weeks, respective plasma fluoride levels were 0.0541 ± 0.0135 μg/ml (control), 0.0596 ± 0.0202 μg/ml (10 ppm), and 0.0823 ± 0.0199 μg/ml (50 ppm). Although plasma glucose levels were not altered in any group, the plasma insulin level in the fluoride (50 ppm) group was elevated (0.72 ± 0.13 μg/ml) versus the control group (0.48 ± 0.24 μg/ml) and fluoride (10 ppm) group. In rats receiving fluoride for 4 weeks at 10 ppm in drinking water, [3H]glucose uptake was unaltered in all tested parts of the brain. However, in rats receiving fluoride at 50 ppm, [3H]glucose uptake in cerebral cortex, hippocampus, and thalamus with hypothalamus was elevated, versus the saline group. Fluoride intake had a negligible effect on [3H]glucose uptake by peripheral tissues (liver, pancreas, stomach, small intestine, atrium, aorta, kidney, visceral tissue, lung, skin, oral mucosa, tongue, salivary gland, incisor, molars, and jawbone). In neither fluoride group was glucose transporter proteins 1 (GLUT 1) or 3 (GLUT 3) altered in frontal cortex and striatum versus control. On the assumption that increased glucose uptake (by neural tissue) reasonably reflects neuronal activity, it appears that fluoride damage to the brain results in a compensatory increase in glucose uptake and utilization without changes in GLUT 1 and GLUT 3 expression.

  10. Imaging cellular and subcellular structure of human brain tissue using micro computed tomography

    Science.gov (United States)

    Khimchenko, Anna; Bikis, Christos; Schweighauser, Gabriel; Hench, Jürgen; Joita-Pacureanu, Alexandra-Teodora; Thalmann, Peter; Deyhle, Hans; Osmani, Bekim; Chicherova, Natalia; Hieber, Simone E.; Cloetens, Peter; Müller-Gerbl, Magdalena; Schulz, Georg; Müller, Bert

    2017-09-01

    Brain tissues have been an attractive subject for investigations in neuropathology, neuroscience, and neurobiol- ogy. Nevertheless, existing imaging methodologies have intrinsic limitations in three-dimensional (3D) label-free visualisation of extended tissue samples down to (sub)cellular level. For a long time, these morphological features were visualised by electron or light microscopies. In addition to being time-consuming, microscopic investigation includes specimen fixation, embedding, sectioning, staining, and imaging with the associated artefacts. More- over, optical microscopy remains hampered by a fundamental limit in the spatial resolution that is imposed by the diffraction of visible light wavefront. In contrast, various tomography approaches do not require a complex specimen preparation and can now reach a true (sub)cellular resolution. Even laboratory-based micro computed tomography in the absorption-contrast mode of formalin-fixed paraffin-embedded (FFPE) human cerebellum yields an image contrast comparable to conventional histological sections. Data of a superior image quality was obtained by means of synchrotron radiation-based single-distance X-ray phase-contrast tomography enabling the visualisation of non-stained Purkinje cells down to the subcellular level and automated cell counting. The question arises, whether the data quality of the hard X-ray tomography can be superior to optical microscopy. Herein, we discuss the label-free investigation of the human brain ultramorphology be means of synchrotron radiation-based hard X-ray magnified phase-contrast in-line tomography at the nano-imaging beamline ID16A (ESRF, Grenoble, France). As an example, we present images of FFPE human cerebellum block. Hard X-ray tomography can provide detailed information on human tissues in health and disease with a spatial resolution below the optical limit, improving understanding of the neuro-degenerative diseases.

  11. Two-stage multishape segmentation of brain structures using image intensity, tissue type, and location information.

    Science.gov (United States)

    Akhondi-Asl, Alireza; Soltanian-Zadeh, Hamid

    2010-08-01

    The authors propose a fast, robust, nonparametric, entropy-based, coupled, multishape approach to segment subcortical brain structures from magnetic resonance images (MRIs). The proposed method uses three types of information: Image intensity, tissue types, and locations of structures. The image intensity information is captured by estimating the probability density function (pdf) of the image intensities in each structure. The tissue type information is captured by applying an unsupervised tissue segmentation method to the image and estimating a probability mass function (pmf) for the tissue type of each structure. The location information is captured by estimating pdf of the location of each structure from the training datasets. The resulting pmf's and pdf's are used to define an entropy function whose minimum corresponds to a desirable segmentation of the structures. The authors propose a three-step optimization strategy for the segmentation method. In the first step, a powerful automatic initialization method is developed based on tissue type and location information of the structures. In the second step, a quasi-Newton method is used to optimize the parameters of the energy function. To speed up the iterations, derivatives of the energy function with respect to its parameters are analytically derived and used in the optimization process. In the last step, the limitations related to the prior shape model are removed and a level-set method is applied for the fine tuning of the segmentation results. The proposed method is applied to two different datasets and the results are compared to those of previous methods in literature. Experimental results are presented for lateral ventricles, caudate, thalamus, putamen, pallidum, hippocampus, and amygdala. The results illustrate superior performance of the proposed segmentation method compared to other methods in literature. The execution time of the algorithm is a few minutes, suitable for a variety of applications.

  12. Fixation-dependent vimentin immunoreactivity of mono- and polyclonal antibodies in brain tissue of cattle, rabbits, rats and mice.

    Science.gov (United States)

    Urban, K; Hewicker-Trautwein, M

    1994-12-01

    The immunohistochemical staining of vimentin in paraffin-embedded sections from adult cattle, rabbit, rat and mouse brain fixed in different fixatives (formaldehyde, methacarn, ethanol) was examined using two monoclonal antibodies and a polyclonal antiserum. In non-trypsinized formaldehyde-fixed tissue sections both monoclonal antibodies and the polyclonal antibodies failed to stain vimentin. Following trypsinization of formaldehyde-fixed sections of the four species the meninges, endothelial cells of blood vessels, ependymal cells and the stroma of the choroid plexus were labelled by the monoclonal and polyclonal antibodies used. Astrocytes and Bergmann glial fibers in pretrypsinized formaldehyde-fixed sections from cattle, rabbit and rat brain, however, showed only weak staining. Fixation of cattle and rat brain in methacarn markedly improved the vimentin immunoreactivity of astrocytes and Bergmann glial fibers. The best fixative for the preservation of immunoreactive determinants of vimentin in astrocytes and Bergmann glial fibers in cattle, rabbit and rat brain was ethanol. In brain tissue from mice both monoclonal antibodies labelled only mesoderm-derived tissue components, but did not recognize vimentin in astrocytes and Bergmann glial fibers. Pre-heating formaldehyde-fixed sections from cattle, rabbit and rat brain in a microwave oven prior to the immunohistochemical reaction resulted in an enormous enhancement of vimentin staining of mesoderm-derived tissues, of astrocytes and bergmann cell fibers.

  13. Correlative analysis of head kinematics and brain's tissue response: a computational approach toward understanding the mechanisms of blast TBI

    Science.gov (United States)

    Sarvghad-Moghaddam, H.; Rezaei, A.; Ziejewski, M.; Karami, G.

    2017-11-01

    Upon impingement of blast waves on the head, stress waves generated at the interface of the skull are transferred into the cranium and the brain tissue and may cause mild to severe blast traumatic brain injury. The intensity of the shock front, defined by the blast overpressure (BoP), that is, the blast-induced peak static overpressure, significantly affects head kinematics as well as the tissue responses of the brain. While evaluation of global linear and rotational accelerations may be feasible, an experimental determination of dynamic responses of the brain in terms of intracranial pressure (ICP), maximum shear stress (MSS), and maximum principal strain (MPS) is almost impossible. The main objective of this study is to investigate possible correlations between head accelerations and the brain's ICP, MSS, and MPS. To this end, three different blasts were simulated by modeling the detonation of 70, 200, and 500 g of TNT at a fixed distance from the head, corresponding to peak BoPs of 0.52, 1.2, and 2 MPa, respectively. A nonlinear multi-material finite element algorithm was implemented in the LS-DYNA explicit solver. Fluid-solid interaction between the blast waves and head was modeled using a penalty-based method. Strong correlations were found between the brain's dynamic responses and both global linear and rotational accelerations at different blast intensities (R^{2 }≥98%), implying that global kinematic parameters of the head might be strong predictors of brain tissue biomechanical parameters.

  14. Correlative analysis of head kinematics and brain's tissue response: a computational approach toward understanding the mechanisms of blast TBI

    Science.gov (United States)

    Sarvghad-Moghaddam, H.; Rezaei, A.; Ziejewski, M.; Karami, G.

    2017-09-01

    Upon impingement of blast waves on the head, stress waves generated at the interface of the skull are transferred into the cranium and the brain tissue and may cause mild to severe blast traumatic brain injury. The intensity of the shock front, defined by the blast overpressure (BoP), that is, the blast-induced peak static overpressure, significantly affects head kinematics as well as the tissue responses of the brain. While evaluation of global linear and rotational accelerations may be feasible, an experimental determination of dynamic responses of the brain in terms of intracranial pressure (ICP), maximum shear stress (MSS), and maximum principal strain (MPS) is almost impossible. The main objective of this study is to investigate possible correlations between head accelerations and the brain's ICP, MSS, and MPS. To this end, three different blasts were simulated by modeling the detonation of 70, 200, and 500 g of TNT at a fixed distance from the head, corresponding to peak BoPs of 0.52, 1.2, and 2 MPa, respectively. A nonlinear multi-material finite element algorithm was implemented in the LS-DYNA explicit solver. Fluid-solid interaction between the blast waves and head was modeled using a penalty-based method. Strong correlations were found between the brain's dynamic responses and both global linear and rotational accelerations at different blast intensities (R^{2 }≥ 98%), implying that global kinematic parameters of the head might be strong predictors of brain tissue biomechanical parameters.

  15. Brain herniation

    Science.gov (United States)

    ... 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 ...

  16. Some growth factors in neoplastic tissues of brain tumors of different histological structure

    Directory of Open Access Journals (Sweden)

    O. I. Kit

    2016-01-01

    Full Text Available Introduction. Pathologic angiogenesis is typical for angiogenic diseases including tumor growth. Vascular endothelial growth factor (VEGF, fibroblast growth factor (FGF, transforming growth factor alpha and beta (which are also known as “triggers” of angiogenesis, and other factors (Gacche, Meshram, 2013; Nijaguna et al., 2015 play a special role in its development. Evaluation of the important mechanisms of angiogenesis in physiological and pathological conditions remains to be a subject of heightened interest for the past 30 years. It is known that VEGF A is the main trigger of growing blood vessels into the tumor tissue. This is specific mitogen signal for endothelial cells that triggers the mechanisms of cell division and migration. VEGF-induced tumor vasculature has a number of structural and functional features that provide growth and progression of tumors, including increased permeability of blood vessels and their chaotic arrangement.Objective: to study in comparative aspect the level of certain growth factors in the following tissues: glioblastomas, brain metastasis of the breast cancer, meningiomas as well as corresponding peritumoral areas.Materials and methods. Tissue samples were obtained from 56 patients admitted to the surgical treatment in Rostov Research Institute of Oncology: 24 patients had glioblastomas, 19 patients had brain metastasis of the breast cancer, 13 patients with meningiomas without peritumoral edema. Histological control was carried out in all cases. Age of patients ranged from 35 to 72 years. The level of growth factor was detected in the samples of tumor tissue and regions immediately adjacent to the tumor foci (peritumoral area by the method of immunoassay and using standard test systems. The following growth factor were detected: VEGF-A and its receptors VEGF-R1 (BenderMedSystem, Austria, VEGF-C and its receptor VEGF-R3 (BenderMedSystem, Austria, EGF (Biosource, USA, IFR-1 and IFR-2 (Mediagnost, USA, TGF

  17. Liver transplant

    Science.gov (United States)

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  18. Regulatory T cells ameliorate tissue plasminogen activator-induced brain haemorrhage after stroke.

    Science.gov (United States)

    Mao, Leilei; Li, Peiying; Zhu, Wen; Cai, Wei; Liu, Zongjian; Wang, Yanling; Luo, Wenli; Stetler, Ruth A; Leak, Rehana K; Yu, Weifeng; Gao, Yanqin; Chen, Jun; Chen, Gang; Hu, Xiaoming

    2017-07-01

    Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia. This study assessed the impact of regulatory T cells in the context of tPA-induced brain haemorrhage and investigated the underlying mechanisms of action. The number of circulating regulatory T cells in stroke patients was dramatically reduced soon after stroke onset (84 acute ischaemic stroke patients with or without intravenous tPA treatment, compared to 115 age and gender-matched healthy controls). Although stroke patients without tPA treatment gradually repopulated the numbers of circulating regulatory T cells within the first 7 days after stroke, post-ischaemic tPA treatment led to sustained suppression of regulatory T cells in the blood. We then used the murine suture and embolic middle cerebral artery occlusion models of stroke to investigate the therapeutic potential of adoptive regulatory T cell transfer against tPA-induced haemorrhagic transformation. Delayed administration of tPA (10 mg/kg) resulted in haemorrhagic t