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Head Trauma Release of Histamine from Dural Mast Cells Alters Blood-Brain Barrier: Attenuation with Zolantidine

Description: This study employed a new model of mild-to-moderate head trauma to specifically identify the role of dural mast cell (MC) histamine in trauma-induced increased permeability in the blood-brain barrier (BBB). A single line was scored partially through the left dorsal parietal skull. Immediately following the trauma, degranulation was seen in 39% of the MCs on the left and in 2% on the right. After a 20 min survival period, left duras showed 55% with MC degranulation (fewer with complete degranulation) compared to 34% on the right. In the other experiments two parallel lines were scored following the injection of Evan's blue. Histamine assay showed histamine increased in the left cortex to 154% at 5 min, 174% at 10 min, and 151% at 20 min. Fluorescent quantitation of extravasated Evan's blue at 20 min following the trauma gave an increase of 1385% over the value measured for the right cortex. Zolantidine, a selective histamine H2 receptor antagonist, administered at 10- and 20- mg/kg 30 min before the trauma blocked 65% of the Evan's blue extravasation compared with the control and 2.5 mg group.
Date: December 2000
Creator: Laufer, Susan R.
Partner: UNT Libraries

The Passage of Sodium-24 and Rubidium-86 Across the Blood-Brain Barrier System of Canines at Low Body Temperatures

Description: To evaluate the blood-brain barrier system in the pathogenesis of an irreversible hypothermic state in dogs, concentrations of 2 4 Na and 86Rb were measured at body temperatures ranging from 37 0 C to 160 C. A suppression of transport of sodium was demonstrated, followed by an increase as the temperature was lowered. The concentration of rubidium ion increased in concentration as the temperature fell. These data indicate there may be a temperature threshold below which the blood-brain barrier system fails to maintain the internal environment of the central nervous system. The intimate relationship of several brain stem nuclei with the cerebro-spinal fluid indicates they may be at risk during profound cooling.
Date: May 1976
Creator: Burgess, Michael Clifton
Partner: UNT Libraries

Tissue biodistribution of intravenously administrated titanium dioxide nanoparticles revealed blood-brain barrier clearance and brain inflammation in rat

Description: This article reports time-related responses from single-dose intravenous administration of 1 mg/kg Ti₂ NPs to rats, with particular emphasis on titanium quantification in the brain.
Date: September 4, 2015
Creator: Disdier, Clémence; Devoy, Jérôme; Cosnefroy, Anne; Chalansonnet, Monique; Herlin-Boime, Nathalie; Brun, Emilie et al.
Partner: UNT College of Arts and Sciences

Brain Inflammation, Blood Brain Barrier dysfunction and Neuronal Synaptophysin Decrease after Inhalation Exposure to Titanium Dioxide Nano-aerosol in Aging Rats

Description: This article focuses on the consequences of TiO₂ distribution on the central nervous system and particularly on the blood-brain barrier functions.
Date: June 15, 2017
Creator: Disdier, Clémence; Chalansonnet, Monique; Gagnaire, François; Gaté, Laurent; Cosnier, Frédéric; Devoy, Jérôme et al.
Partner: UNT College of Arts and Sciences

Final Scientific/Technical Report

Description: We started to use the first animal model of provoked status epilepticus to test the hypothesis that acute seizures induced by osmotic disruption of the blood-brain barrier result in delayed epileptogenesis. These initial experiments were aimed at perfecting the technique used. One of the problems with the approach used in the past is the fact that intarterial injections are performed across an open incision, which does not allow survival. They have therefore changed the surgical approach as detailed in this paper.
Date: September 1, 2011
Creator: Janigro, Damir
Partner: UNT Libraries Government Documents Department

Exposure to vehicle emissions results in altered blood brain barrier permeability and expression of matrix metalloproteinases and tight junction proteins in mice

Description: Article on the exposure to vehicle emissions results in altered blood brain barrier permeability and expression of matrix metalloproteinases and tight junction proteins in mice.
Date: June 18, 2013
Creator: Oppenheim, Hannah A.; Lucero, JoAnn; Guyot, Anne-Cécile; Herbert, Lindsay M.; McDonald, Jacob D.; Mabondzo, Aloïse et al.
Partner: UNT College of Arts and Sciences

A Phase 1 trial of intravenous boronophenylalanine-fructose complex in patients with glioblastoma multiforme

Description: Boron neutron capture therapy (BNCT) of glioblastoma multiforme was initially performed at the Brookhaven National Laboratory in the early 1950`s While this treatment for malignant brain tumors has continued in Japan, new worldwide interest has been stimulated by the development of new and more selective boron compounds. Boronophenylalanine (BPA) is a blood-brain barrier penetrating compound that has been used in BNCT of malignant melanomas. SPA has been employed experimentally in BNCT of rat gliosarcoma and has potential use in the treatment of human glioblastoma. As a preface to clinical BNCT trials, we studied the biodistribution of SPA in patients with glioblastoma.
Date: October 1, 1996
Creator: Bergland, R.; Elowitz, E.; Chadha, M.; Coderre, J.A. & Joel, D.
Partner: UNT Libraries Government Documents Department

Development of Gamma-Emitting Receptor Binding Radiopharmace

Description: The long-term objective is to develop blood-brain barrier (BBB) permeable m2-selective (relative to m1, m3, and m4) receptor-binding radiotracers and utilize these radiotracers for quantifying receptor concentrations obtained from PET or SPECT images of human brain. In initial studies, we concluded that the lipophilicity and high affinity prevented (R,S)-I-QNB from reaching a flow-independent and receptor-dependent state in a reasonable time. Thus, it was clear that (R,S)-I-QNB should be modified. Therefore, during the last portion of this funded research, we proposed that more polar heterocycles should help accomplish that. Since reports of others concluded that radiobromination and radiofluorination of the unactivated phenyl ring is not feasible (Newkome et al,,1982), we, therefore, explored during this grant period a series of analogues of (R)-QNB in which one or both of the six-membered phenyl rings is replaced by a five-membered thienyl (Boulay et al., 1995), or furyl ring. The chemistry specific aims were to synthesize novel compounds designed to be m2-selective mAChR ligands capable of penetrating into the CNS, and develop methods for efficient radiolabeling of promising m2-selective muscarinic ligands. The pharmacology specific aims were to determine the affinity and subtype-selectivity of the novel compounds using competition binding studies with membranes from cells that express each of the five muscarinic receptor subtypes, to determine the ability of the promising non-radioactive compounds and radiolabeled novel compounds to cross the BBB, to determine the biodistribution, in-vivo pharmacokinetics, and in-vitm kinetics of promising m2-selective radioligands and to determine the distribution of receptors for the novel m2-selective radioligands using quantitative autoradiography of rat brain, and compare this distribution to the distribution of known m2-selective compounds.
Date: February 20, 2003
Creator: Reba, Richard
Partner: UNT Libraries Government Documents Department

Biomolecular interactions and responses of human epithelial and macrophage cells to engineered nanomaterials.

Description: Engineered nanomaterials (ENMs) are increasingly being used in commercial products, particularly in the biomedical, cosmetic, and clothing industries. For example, pants and shirts are routinely manufactured with silver nanoparticles to render them 'wrinkle-free.' Despite the growing applications, the associated environmental health and safety (EHS) impacts are completely unknown. The significance of this problem became pervasive within the general public when Prince Charles authored an article in 2004 warning of the potential social, ethical, health, and environmental issues connected to nanotechnology. The EHS concerns, however, continued to receive relatively little consideration from federal agencies as compared with large investments in basic nanoscience R&D. The mounting literature regarding the toxicology of ENMs (e.g., the ability of inhaled nanoparticles to cross the blood-brain barrier; Kwon et al., 2008, J. Occup. Health 50, 1) has spurred a recent realization within the NNI and other federal agencies that the EHS impacts related to nanotechnology must be addressed now. In our study we proposed to address critical aspects of this problem by developing primary correlations between nanoparticle properties and their effects on cell health and toxicity. A critical challenge embodied within this problem arises from the ability to synthesize nanoparticles with a wide array of physical properties (e.g., size, shape, composition, surface chemistry, etc.), which in turn creates an immense, multidimensional problem in assessing toxicological effects. In this work we first investigated varying sizes of quantum dots (Qdots) and their ability to cross cell membranes based on their aspect ratio utilizing hyperspectral confocal fluorescence microscopy. We then studied toxicity of epithelial cell lines that were exposed to different sized gold and silver nanoparticles using advanced imaging techniques, biochemical analyses, and optical and mass spectrometry methods. Finally we evaluated a new assay to measure transglutaminase (TG) activity; a potential marker for cell toxicity.
Date: December 1, 2011
Creator: Kotula, Paul Gabriel; Brozik, Susan Marie; Achyuthan, Komandoor E.; Greene, Adrienne Celeste; Timlin, Jerilyn Ann; Bachand, George David et al.
Partner: UNT Libraries Government Documents Department

Design, synthesis and evaluation of 2-deoxy-2-iodovinyl-branched carbohydrates as potential brain imaging agents

Description: Radioiodinated carbohydrates such as 2-deoxy-2-iodo-D-glucose and 3-deoxy-3-iodo-D-glucose undergo facile chemical or in vivo deiodination which precludes their use as radiotracers of glucose metabolism in tissues. To overcome the problems resulting from in vivo deiodination, we explored the concept of stabilizing radioiodide on a model carbohydrate, (E)-C-3-iodovinyl-D-allose (10) as an iodovinyl moiety. This agent did not exhibit brain specificity but showed low in vivo deiodination which demonstrated for the first time that radioiodide can be stabilized on a carbohydrate. The goal of this study was to develop a deoxy-branched carbohydrate with radioiodide stabilized as a vinyliodide with the objective of achieving high brain uptake. 10 refs., 1 fig., 1 tab.
Date: January 1, 1986
Creator: Goodman, M.M.; Callahan, A.P. & Knapp, F.F. Jr.
Partner: UNT Libraries Government Documents Department

Biological efficacy of a boronated porphyrin as measured in cell culture

Description: Attempts to develop a boronated porphyrin analog have suffered from problems associated with toxicity, solubility and, upon occasion, lability of the boron tag. One compound synthesized by one of us (SBK), designated ''SBK-II'', has evidently overcome the above problems, providing therapeutic amounts of boron in animal tumor models (20-40 ..mu..g B/g tumor) with retention times in the order of weeks. As is well known, biological efficacy will depend upon distribution within (or without) the cell. In the experiments detailed here, biological efficacy has been evaluated in Hamster V-79 cells, irradiated at the thermal neutron beam at the Brookhaven Medical Research Reactor, using irradiation geometries and techniques as described in detail elsewhere. Cell survival curves obtained with 15 and 29 ..mu..g /sup 10/B per ml from H/sub 3//sup 10/BO/sub 3/ (''ambient'' conditions) were compared to a control (no boron) curve (data not shown). 2 refs., 3 figs., 1 tab.
Date: January 1, 1987
Creator: Laster, B.H.; Kahl, S.B.; Kalef-Ezra, J.; Popenoe, E.A. & Fairchild, R.G.
Partner: UNT Libraries Government Documents Department

Design, synthesis and evaluation of redox radiopharmaceuticals: a potential new approach for the development of brain imaging agents

Description: The fabrication and complete evaluation are described of a dihydropyridine in equilibrium pyridinium salt type redox system for the delivery of radioiodinated agents to the brain. The pivotal intermediate, N-succinimidyl (1-methylpyridinium iodide)-3-carboxylate was prepared by condensation of nicotinic acid and N-hydroxysuccinimide in the presence of dicyclohexylcarbodimide, followed by quaternization of III with methyl iodide. Tissue distribution studies of /sup 125/I-labeled 4-iodoaniline and the redox agents were performed in rats. (/sup 125/I)Iodoaniline initially showed moderate (0.58% dose/gm) brain uptake with subsequent release of the radioactivity from the brain. (/sup 125/I)Iodoaniline, when coupled to a dihydropyridine carrier showed higher uptake and retention in the brain. The (/sup 125/I)iodophenylethyl analogue showed uptake and retention in the brain to be very similar. Apparently the lipophilic agents cross the blood-brain barrier and are oxidized (quaternized) within the brain. The blood-brain barrier then prevents their release resulting in high uptake and retention in the brain and high brain:blood ratios. 11 refs., 3 figs.
Date: January 1, 1986
Creator: Srivastava, P.C. & Knapp, F.F. Jr.
Partner: UNT Libraries Government Documents Department

Potential new approaches for the development of brain imaging agents for single-photon applications

Description: This paper describes new strategies for the brain-specific delivery of radionuclides that can be used to evaluate regional cerebral perfusion by single photon imaging techniques. A description of several examples of interesting new strategies that have recently been reported is presented. A new approach at this institution for the brain-specific delivery of radioiodinated iodophenylalkyl-substituted dihyronicotinamide systems is described which shows good brain uptake and retention in preliminary studies in rats. Following transport into the brain these agents appear to undergo facile intracerebral oxidation to the quaternized analogues which do not recross the intact blood-brain barrier and so are effectively trapped in the brain. 49 refs., 9 figs., 1 tab.
Date: January 1, 1984
Creator: Knapp, F.F. Jr. & Srivastava, P.C.
Partner: UNT Libraries Government Documents Department