bluuebunny/crossref_metadata_2025_split huggingface dataset:
Traumatic Brain Injury‐Induced Excitotoxicity Assessed in a Controlled Cortical Impact Model
Authors: Palmer Alan M. , Marion Donald W. , Botscheller Michelle L. , Swedlow Pamela E. , Styren Scott D. , DeKosky Steven T. 
Published: October 2006

AbstractUsing a controlled cortical impact model of traumatic brain injury (TBI) coupled with tissue microdialysis, interstitial concentrations of aspartate and glutamate (together with serine and glutamine) were assessed in rat frontal cortex. Histological analysis indicated that the severity of injury following severe TBI (depth of deformation = 3.5 mm) was approximately twice that occurring following moderate TBI (depth of deformation = 1.5 mm). Both groups demonstrated significant postinjury maximal increases in excitatory amino acid (EAA) concentration, which were proportional to the severity of injury. The mean ± SEM fold increase in dialysate concentrations of aspartate was 38 ± 13 (n = 5) for moderate TBI and 74 ± 12 (n = 5) for severe TBI. Fold increases in glutamate concentrations were 81 ± 26 and 144 ± 23 for moderate and severe TBI, respectively. Although these increases normalized within 20–30 min following moderate TBI, concentrations of aspartate and glutamate took >60 min to normalize after severe TBI. Changes in levels of nontransmitter amino acids were much smaller. Fold increases for serine concentrations were 4.6 ± 0.6 and 7.6 ± 1.7 in moderate and severe TBI, respectively; glutamine concentrations had similar small fold increases (2.6 ± 0.2 and 4.1 ± 0.6, respectively). Calculation of interstitial concentrations following severe TBI indicated that aspartate and glutamate maximally increased to 123 ± 20 and 414 ± 66 μM, respectively. To determine the extent to which such tissue concentrations of EAAs could contribute to the injury seen in TBI, the EAA receptor agonists N‐methyl‐d‐ aspartate and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid were slowly injected into rat cortex. Remarkably similar histological injuries were produced by this procedure, supporting the notion that TBI is an excitotoxic injury.
Immunochemical Characterization of the β2 Subunit of the GABAA Receptor
Authors: Machu Tina K. , Olsen Richard W. , Browning Michael D. 
Published: October 2006

AbstractTo date three β subunits of the GABAA receptor have been identified in rat brain as a result of cDNA library screening. The β2 subunit has been reported to have a wide distribution in rat brain based on in situ hybridization studies quantifying β2 mRNA. To study the β2 subunit more directly, we have raised a polyclonal antibody to a synthetic peptide representing residues 315–334 of the intracellular loop of the β2 subunit. The antibody, which had been affinity‐purified, recognized the β2 peptide but did not immunolabel homologous β1 and β3 subunit peptides, indicating that this antibody is specific for the β2 subunit of the receptor. In western blots of the purified receptor, the antibody recognized a major diffuse band of 54–58 kDa arid exhibited minor labeling of lower‐molecular‐mass polypeptides. In western blots of cortex homogenate, the antibody exhibited nervous system‐specific labeling of a 55‐kDa band that comigrated with the 55‐kDa band of the purified receptor. Quantitative immunolabeling of this 55‐kDa polypeptide permitted direct determination of the relative amounts of the β2 subunit in different brain regions. The brainstem contained the highest relative specific activity of the β2 subunit, followed by the inferior colliculus, olfactory lobe, and cerebellum. Lower levels of immunolabeling were seen in hypothalamus, hippocampus, thalamus, and cortex.
Regionaland Interspecies Differences in Brain Progesterone Metabolism
Authors: Korneyev A. , Guidotti A. , Costa E. 
Published: October 2006

AbstractMetabolites of [3H]progesterone were studied in slices prepared from different brain regions of male rat, mouse, and monkey. The major metabolites were 5α‐dihydroprogesterone (5α‐DHP) and 3α,5α‐tetrahydroprogesterone (3α,5α‐THP) in rat brain slices, 5α‐DHP and 20α‐ dihydroprogesterone (20α‐DHP) in mouse brain slices, and 20α‐DHP in monkey brain slices. In rat olfactory bulb slices, 5α‐DHP represented 25.2 ± 3.3% of total radioactivity and 3α,5α‐THP 17.5 ± 2.8%, whereas in rat medulla oblongata slices, 5α‐DHP was 31.3 ± 3.5% and 3α,5α‐ THP 5.4 ± 1.5% of total radioactivity. In slices from other rat brain regions, both metabolites represented 12–20% of total radioactivity.‐The highest metabolite content in mouse brain was also detected in olfactory bulb slices, where 5α‐DHP represented 16.6 ± 4.6% and 20α‐DHP 9.5 ± 2.3% of total radioactivity. In cortical and corpus callosum slices of monkey brain, 26.8 ± 4.4% and 2.4 ± 0.5% of total radioactivity, respectively, were converted to 20α‐DHP, and less than 3% of total radioactivity could be attributed to any of the other metabolites detected. The 3α,α‐THP content in both rat and monkey brain was below 1 nM, but increased in rat brain to 6.7 ± 2.5 nM after electroshock. Endogenous 3α,5α‐THP might play an important role in the regulation of rat behavior through the modulation of GABA action on the GABAA receptor. The significant interspecies differences in the brain progesterone metabolism should be considered in evaluating the functional role of neurosteroids in various species.
Amino Acid Neurotransmitters in Nucleus Tractus Solitarius: An In Vivo Microdialysis Study
Authors: Sved Alan F. , Curtis J. Thomas 
Published: October 2006

AbstractAmino acid neurotransmitters in the nucleus tractus solitarius (NTS) are thought to play a key role in the mediation of visceral reflexes and glutamate has been proposed as the neurotransmitter of visceral afferent nerves projecting to this region. The present studies sought to characterize the use of in vivo microdialysis to examine extracellular fluid levels of amino acids in the NTS of anesthetized rats. Using a microdialysis probe that was 450 μm in length and a sensitive HPLC assay for amino acids, amino acids could be measured in dialysate samples collected from the NTS. Perfusion of the microdialysis probe with 60 mM K±, to elicit depolarization of nerve terminals in the vicinity of the probe, resulted in increased dialysate fluid levels of aspartate, glutamate, glycine, taurine, and GABA. In contrast, glutamine and tyrosine were decreased and other amino acids were not significantly affected. Prior removal of the ipsilateral nodose ganglion did not alter the K±‐evoked changes in dialysate levels of any of these amino acids. Electrical stimulation of the vagus nerves, using a variety of stimulus parameters, did not significantly alter dialysate levels of glutamate or any of the other amino acids that were measured. Blockade of glutamate uptake with dihydrokainate increased dialysate levels of glutamate, aspartate, and GABA, but in the presence of dihydrokainate vagal stimulation did not alter dialysate levels of these amino acids. The results show that in vivo microdialysis can be used to examine amino acid efflux in the rat NTS and provide further evidence for amino acidergic neural transmission in the NTS. However, these studies fail to support the hypothesis that vagal afferents release glutamate or aspartate.
Inhibition of Glutamate Uptake with l‐trans‐Pyrrolidine‐2,4‐Dicarboxylate Potentiates Glutamate Toxicity in Primary Hippocampal Cultures
Authors: Robinson Michael B. , Djali Sina , Buchhalter Jeffrey R. 
Published: October 2006

AbstractSodium‐dependent, high‐affinity glutamate transport is generally assumed to limit the toxicity of glutamate in vivo and in vitro, but there is very little direct evidence to support this hypothesis. In the present study, the effects of the specific uptake inhibitor l‐trans‐pyrrolidine‐2,4‐dicarboxylate on the toxicity and clearance of glutamate were examined in hippocampal neuronal cultures. At a concentration that was not toxic by itself, l‐trans‐pyrrolidine‐2,4‐dicarboxylate increased the toxicity of glutamate approximately fivefold and slowed the clearance of glutamate from the extracellular space. This toxicity was almost completely blocked by the N‐methyl‐d‐aspartate receptor antagonist, d‐2‐amino‐5‐phosphonopentanoate. These studies provide direct evidence that sodium‐dependent, high‐affinity glutamate transport limits glutamate toxicity in vitro.
Epitope Mapping of Form‐Specific and Nonspecific Antibodies to Acetylcholinesterase
Authors: Wasserman Linda , Doctor Bhupendra P. , Gentry Mary K. , Taylor Palmer 
Published: October 2006

AbstractWe have mapped the epitopes to which two monoclonal antibodies against acetylcholinesterase (AChE) from Torpedo californica are directed. One antibody, 2C9, has equivalent affinity for both the 5.6S (amphiphilic) and 11S (hydrophilic) enzyme forms; the other, 4E7, recognizes only the amphiphilic form and has been shown previously to require an N‐linked oligosaccharide residue on the protein. Isolation of cyanogen bromide peptides from the amphiphilic form and assay by a competition ELISA for 2C9 and by a direct binding ELISA for 4E7 identified the same peptide, residues 44–82, as containing epitopes against both antibodies. The epitope for 4E7 includes the oligosaccharide conjugated to Asp59, an N‐linked glycosylation site not present in mouse AChE. A 20‐amino‐acid synthetic peptide, RFRRPEPKKPWSQVWNASTY, representing residues 44–63, was synthesized and found to inhibit completely 2C9 binding to 5.6S enzyme at molar concentrations comparable to those of the cyanogen bromide peptide. It was unreactive with 4E7. Fractionation of the synthetic peptide further localized the 2C9 epitope. Peptides RFRRPEPKKPW and KPWSGVWNASTY both reacted but less so than the entire synthetic peptide at equivalent molar concentrations, whereas the peptide RPEPKKPWSGVWNASTY was as effective as the larger synthetic peptide. The crystal structure of AChE shows the peptide to be on the surface of the molecule as part of a convex hairpin loop starting before the first α‐helix.
pH‐Dependent Binding of Synthetic β‐Amyloid Peptides to Glycosaminoglycans
Authors: Brunden Kurt R. , Richter‐Cook Nancy J. , Chaturvedi Nishith , Frederickson Robert C. A. 
Published: October 2006

AbstractThe seinile plaques found within the cerebral cortex and hippocampus of the Alzheimer disease brain contain β‐amyloid peptide (Aβ) fibrils that are associated with a variety of macromolecular species, including dermatan sulfate proteoglycan and heparan sulfate proteoglycan. The latter has been shown recently to bind tightly to both amyloid precursor protein and A/β, and this binding has been attributed largely to the interaction of the core protein of heparan sulfate proteoglycan with Aβ and its precursor. Here we have examined the ability of synthetic Aβ s to bind to and interact with the glycosaminoglycan moieties of proteoglycans. Aβ(1–28) associates with heparin, heparan sulfate, dermatan sulfate, and chondroitin sulfate. The interaction of these sulfated polysaccharides with the amyloid peptide results in the formation of large aggregates that are readily sedimented by centrifugation. The ability of both Aβ(1–28) and Aβ(1–40) to bind glycosaminoglycans is pH‐dependent, with increasing interaction as the pH values fall below neutrality and very little binding at pH 8.0. The pH profile of heparin‐induced aggregation of Aβ(1–28) has a midpoint pH of approximately 6.5, suggesting that one or more histidine residues must be protonated for binding to occur. Analysis of the Aβ sequence reveals a consensus heparin‐binding domain at residues 12–17, and this motif contains histidines at positions 13 and 14 that may be involved in the interaction with glycosaminoglycans. This hypothesis is supported by the following observations: (a) Aβ(13–17) binds tightly to a heparin affinity column at pH 4.0, but not at pH 8.0; and (b) an Aβ(13–17) in which histidine residues 13 and 14 have been replaced with serines does not bind to a heparin column at either pH 8.0 or 4.0. Together, the data indicate that Aβ is capable of binding to the glycosaminoglycan chains of proteoglycans, and such an interaction may be relevant to the etiology and pathology of Alzheimer's disease.
1, 2, 3, 4‐Tetrahydro‐2‐Methyl‐4, 6, 7‐Isoquinolinetriol Depletes Catecholamines in Rat Brain
Authors: Liptrot Janet , Holdup David , Phillipson Oliver 
Published: October 2006

Abstract1, 2, 3, 4‐Tetrahydro‐2‐methyl‐4, 6, 7‐isoquinolinetriol (TMIQ) was synthesised and tested for activity as a dopamine‐depleting agent in rat brain. After intracerebroventricular infusion, TMIQ caused reductions in dopamine concentrations in substantia nigra, striatum, hypothalamus, and dorsal raphe, and reduction in noradrenaline concentrations in locus coeruleus. TMIQ also reduced 5‐hydroxytryptamine concentrations in dorsal raphe and substantia nigra, although with a lower potency. Comparisons between TMIQ and MPTP showed that they were approximately equipotent in depleting dopamine in the substantia nigra, hypothalamus, and dorsal raphe. Pretreatment of animals with a combination of monoamine oxidase A and B inhibitors completely prevented the TMIQ‐induced reductions in dopamine concentrations in substantia nigra and hypothalamus. Direct unilateral intrastriatal injections of TMIQ produced marked ipsilateral reductions in striatal dopamine, correlating with a behavioural response consisting of turning towards the side of injection. The results suggest that TMIQ should be evaluated further as a possible MPTP‐like compound, which may derive from endogenous β‐hydroxylated catecholamines.
Developmental Regulation of mRNAs Encoding Rat Brain Kainate/AMPA Receptors: A Northern Analysis Study
Authors: Durand Guylaine M. , Zukin R. Suzanne 
Published: October 2006

AbstractFunctionally diverse kainate/α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors are generated by assembly of glutamate receptor (GluR)1, 2, and 3 subunits into homomeric and heteromeric channels. We examined GluR1, 2, and 3 gene expression in embryonic, neonatal, and adult rat brain by northern analysis under conditions of high stringency. In the adult, hybridization to a GluR1 riboprobe revealed the presence of an abundant RNA species, 5.2 kb in size, and minor bands of 3.2 and 3.9 kb. GluR2 hybridized to two species, 3.9 and 5.9 kb, of comparable abundance, presumably attributable to alternate splice products. Hybridization to the GluR3 riboprobe showed a major species of 5.2 kb. This pattern of RNA species was invariant over all the brain regions examined. Examination of GluR expression in development revealed that in the postnatal period, GluR1, 2, and 3 mRNAs are regulated as a function of age. In adult rat brain, GluR1 and 2 mRNA expression was highest in hippocampus; GluR3 was expressed at highest density in hippocampus and frontal cortex. The three transcripts were first detected at embryonic day 16 and then exhibited changes in expression levels in a region‐specific manner. In hippocampus, all three transcripts exhibited elevated expression in the late neonatal period; in frontal cortex, elevated expression was observed for GluR2 and 3 only. In striatum, all three transcripts were expressed at relatively low levels throughout development, with a modest peak at postnatal day 14. In cerebellum, the GluR1 mRNA level was high from postnatal day 28 to adult. Studies of recombinant receptors indicate that GluR1 and 3 subunits form channels that are Ca2± permeable; heteromeric receptors containing the GluR2 subunit are Ca2± impermeable. These observations raise the possibility that a modification of GluR2 expression during development may regulate the level of Ca2±‐permeable kainate channels. We therefore investigated the expression of the GluR2 subunit relative to those of the GluR1 and 3 subunits as a function of age. In hippocampus and frontal cortex, the (GluR1 ± GluR3)/GluR2 ratio declined with increasing age. This result provides evidence for a developmental regulation of kainate/AMPA receptor gene expression in the brain during the first 2 weeks of postnatal life and predicts a decrease in glutamate‐operated Ca2± permeability mediated through kainate/AMPA receptors as a function of age.
Sequence and Novel Distribution of the Chicken Homologue of the Mammalian γ‐Aminobutyric AcidA Receptor γ 1 Subunit
Authors: Glencorse Thora A. , Darlison Mark G. , Barnard Eric A. , Bateson Alan N. 
Published: October 2006

AbstractcDNAs have been cloned that encode the chicken (Gallus domesticus) γ‐aminobutyric acidA receptor γ1 subunit, the mature sequence of which shares 90, 79, and 69% identity with those of the rat γ1, γ2., and γ3 subunits, respectively. In situ hybridization reveals that there are pronounced differences in the regional and cellular localizations of the corresponding γ‐aminobutyric acidAreceptor γ‐subunit mRNA compared with that of the γ2‐subunit mRNA in 1 ‐day‐old chick brain. The absence of the γ1‐subunit transcript in certain chick brain nuclei of visual and auditory pathways, in which γ 2‐subunit mRNA is present, points to differences in the functional roles of receptors containing one or other of these polypeptides. Certain cells in other brain regions appear to contain both γ1 ‐ and γ2‐subunit mRNAs, suggesting that they either have two γ‐aminobutyric acidA receptor subtypes or possess receptors incorporating two different γ subunits. We have also found contrasts in the distribution patterns, in homologous brain regions, of the chicken γ1‐subunit mRNA and the rat γ1‐subunit mRNA. These data may reflect different functional roles of the chicken and rat γ1subunits.
Functional Identification and Molecular Cloning of a Human Brain Vesicle Monoamine Transporter
Authors: Erickson Jeffrey D. , Eiden Lee E. 
Published: October 2006

AbstractA vesicle monoamine transporter was functionally identified, molecularly cloned, and characterized from a human substantia nigra cDNA library. The ATP‐dependent transport of 5‐[3H]hydroxytryptamine ([3H]5‐HT) by digitonin‐permeabilized fibroblasts expressing the vesicle monoamine/H± antiporter in culture exhibited a Km of 0.55 μM. Reserpine and tetrabenazine, inhibitors of two monoamine binding sites, effectively blocked [3H]5‐HT accumulation with K1 values of 34 and 78 nM, respectively. Pretreatment of cells with as little as 10 nM reserpine in the presence of ATP abolished uptake. The rank order for substrate inhibition of [3H]5‐HT uptake for both the previously reported rat vMAT1 and the human transporter clone followed the order 5‐HT > dopamine > epinephrine > norepinephrine > 1 ‐methyl‐4‐phen‐ ylpyridinium > 2‐phenylethylamine > histamine. The virtually identical transport characteristics of rvMATI and hvMAT1 confirm the relevance of neuropharmacological studies of rat brain biogenic amine uptake and storage to human brain neurochemistry.
Interior Design Supports Art Education: A Case Study
Authors: Clemons Stephanie A. 
Published: October 2006

AbstractInterior design, as a field of study, is a rapidly growing area of interest — particularly for teenagers in the United States. Part of this interest stems from the proliferation of design‐related reality shows available through television media. Some art educators and curriculum specialists in the nation perceive the study of interior spaces as a ‘practical application’ of the arts.This article discusses an experiential design problem, originally used in higher education interior design studio courses that was modified and shared with students in third grade to address national academic standards. Later, this same project was modified for use with high school students in the educator's community and with international design students in South Korea. Lastly, the project was presented in a workshop to art education students at a higher education institution. The project was modified to address (1) the age group level and (2) a topic relevant to the audience. Goals of the design project were: (1) to explore creative problem‐solving, (2) to explore the application of design elements and principles, and (3) to increase student understanding of spatial relationships within an interior environment. Findings indicate that the project supported several visual art standards, including perception and community. This project may be of interest to current and future art educators and others interested in the potential of interior design content supporting art education.
Coming in From the Cold: Imperialist Legacies and Tactical Criticalities
Authors: Kill Rebekka 
Published: October 2006

AbstractThere is a perception in British universities and art colleges that art students are not very good at writing, that they don't want to write, and furthermore, that writing gets in the way of the real business of making art. These perceptions are reinforced in much of the literature that has been produced about, and in support of, undergraduate art education in the last few decades.This paper will examine the tensions, both historical and contemporary, between academic practices (such as the academic essay, the dissertation) and fine art studio practices. This translative gap both produces, and perpetuates, a set of binaries: visual/textual, art/literature, words/images, Studio/Art History, making/writing. The net result of which is a resistance to writing from many Art students in Higher Education. I will outline subject specific multidisciplinary strategies used with undergraduate and postgraduate students to harness, and develop, this resistance as both transformational and inventive.
Ventriculocordectomy as the Sole Treatment for Recurrent Laryngeal Neuropathy: Long‐Term Results from Ninety‐Two Horses
Authors: TAYLOR SARAH E. , BARAKZAI SAFIA Z. , DIXON PADRAIC 
Published: October 2006

Objective—To evaluate the effect ventriculocordectomy (VC) for treatment of recurrent laryngeal neuropathy (RLN) on exercise performance and owner satisfaction in a mixed‐breed population of horses.Study Design—Retrospective study.Animals—Adult horses (n=92) with a history of abnormal respiratory noise and RLN.Methods—Retrospective analysis of horse that had unilateral VC (and contralateral ventriculectomy in 63 horses) for treatment of idiopathic RLN. Owners/trainers completed a questionnaire about complications and outcome at least 1 year after surgery. Performance index was determined using race records for previously raced Thoroughbreds to evaluate outcome.Results—Clinical signs included abnormal exercise‐induced respiratory noises (noises; 52%), poor performance (11%), and noises and poor performance (37%). The median preoperative resting endoscopic grade of laryngeal function was Havemeyer grade III.1 (mild asymmetry). No discharge from the laryngotomy 1 week postoperatively occurred in 62% horses, 22% coughed after surgery, 66% made no noises, 9% continued to make noises at the canter, 21% made noise at the gallop, and 4% of owners were unsure whether noises were present. Ninety‐three percent of horses returned to full work after surgery. Overall, 86% of owners considered the surgery worthwhile, 3% did not consider it worthwhile, and 11% were unsure. Surgery had a significantly beneficial effect on the racing performance index in Thoroughbreds (P=.004).Conclusions—VC is a useful alternative to laryngoplasty for selected cases of RLN and is associated with a positive effect on exercise performance, a low postoperative complication rate, and a high rate of owner satisfactionClinical Relevance—Unilateral VC should be considered as a sole treatment in horses with low grades of RLN.