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Human Brain Tissue (human + brain_tissue)
Selected AbstractsVisualizing feedback-enhanced contrast in magnetic resonance imagingCONCEPTS IN MAGNETIC RESONANCE, Issue 6 2007Susie Y. Huang Abstract A new approach to magnetic resonance imaging (MRI) contrast enhancement has recently been developed that exploits nonlinear feedback interactions to amplify contrast arising from small variations in the underlying MRI parameters. A unified framework for understanding feedback-enhanced contrast is presented here based on the concepts of instability and positive feedback. The specific mechanisms governing contrast enhancement under the feedback interactions of radiation damping, the distant dipolar field, and their joint effect are elucidated through numerical simulations illustrating the involved spin dynamics. Experimental demonstrations of feedback-enhanced contrast are shown on samples of in vitro human brain tissue, and applications to improving lesion detection in disease states such as epilepsy and cancer are discussed. © 2007 Wiley Periodicals, Inc. Concepts Magn Reson Part A 30A: 378,393, 2007. [source] Association of ABCB1 genetic variants 3435C>T and 2677G>T to ABCB1 mRNA and protein expression in brain tissue from refractory epilepsy patientsEPILEPSIA, Issue 9 2008Igor Mosyagin Summary Purpose: There is evidence from studies in rodents that P-glycoprotein (P-gp) overexpression is implicated in the causation of refractory epilepsy. Genetic variants in the human ABCB1 (MDR1) gene were shown to affect the expression levels of the transporter in various tissues and to be associated with refractory epilepsy. However, the effect of the genetic variants on the P-gp level in epileptogenic brain tissue is poorly investigated. In the present study, we examined the impact of putatively functional polymorphisms 3435C>T and 2677G>T in the ABCB1 gene on the ABCB1 mRNA expression and P-gp content in human brain tissue from epileptogenic foci of the patients with refractory epilepsy. Methods: Fresh brain tissue specimens were obtained from therapy-refractory epilepsy patients during neurosurgery of the epileptogenic focus. We determined the ABCB1 mRNA expression in 23 samples using 5, exonuclease-based real-time polymerase chain reaction (PCR) as well as the P-gp content in 32 samples determined by immunohistochemistry, genotyping was performed by PCR/restriction fragment length polymorphism (RFLP). Results: There was lack of association of 3435C>T and 2677G>T as well as diplotype configurations on ABCB1 mRNA expression and P-gp content in epileptogenic brain tissues. Conclusions: We cannot exclude an association of ABCB1 variants on P-gp function, but our results suggest that brain ABCB1 mRNA and protein expression is not substantially influenced by major ABCB1 genetic variants thus explaining in part results from case-control studies obtaining lack of association of ABCB1 polymorphisms to the risk of refractory epilepsy. [source] Molecular Neuropathology of Temporal Lobe Epilepsy: Complementary Approaches in Animal Models and Human Disease TissueEPILEPSIA, Issue 2007Michael Majores Summary:, Patients with temporal lobe epilepsies (TLE) frequently develop pharmacoresistance to antiepileptic treatment. In individuals with drug-refractory TLE, neurosurgical removal of the epileptogenic focus provides a therapy option with high potential for seizure control. Biopsy specimens from TLE patients constitute unique tissue resources to gain insights in neuropathological and molecular alterations involved in human TLE. Compared to human tissue specimens in most neurological diseases, where only autopsy material is available, the bioptic tissue samples from pharmacoresistant TLE patients open rather exceptional preconditions for molecular biological, electrophysiological as well as biochemical experimental approaches in human brain tissue, which cannot be carried out in postmortem material. Pathological changes in human TLE tissue are multiple and relate to structural and cellular reorganization of the hippocampal formation, selective neurodegeneration, and acquired changes of expression and distribution of neurotransmitter receptors and ion channels, underlying modified neuronal excitability. Nevertheless, human TLE tissue specimens have some limitations. For obvious reasons, human TLE tissue samples are only available from advanced, drug-resistant stages of the disease. However, in many patients, a transient episode of status epilepticus (SE) or febrile seizures in childhood can induce multiple structural and functional alterations that after a latency period result in a chronic epileptic condition. This latency period, also referred to as epileptogenesis, cannot be studied in human TLE specimens. TLE animal models may be particularly helpful in order to shed characterize new molecular pathomechanisms related to epileptogenesis and open novel therapeutic strategies for TLE. Here, we will discuss experimental approaches to unravel molecular,neuropathological aspects of TLE and highlight characteristics and potential of molecular studies in human and/or experimental TLE. [source] Cellular localization and expression patterns of interleukin-10, interleukin-4, and their receptors in multiple sclerosis lesionsGLIA, Issue 1 2002Sandra Hulshof Abstract Cytokines have been shown to play a crucial role in the pathogenesis of multiple sclerosis (MS). However, still limited data are available on the expression of anti-inflammatory cytokines within the central nervous system (CNS) during MS lesion development. Therefore, we have examined the expression of the anti-inflammatory cytokines, interleukin-10 (IL-10) and IL-4, and their specific receptors, IL-10R and IL-4R, in postmortem human brain tissue obtained from MS patients. Specific patterns of protein localization and expression for both proteins could be observed within active and chronic MS lesions. Strongest IL-10 immunoreactivity was observed in reactive astrocytes within active demyelinating lesions and the hypercellular rim of chronic active MS lesions. Moreover, perivascular macrophages were immunoreactive for IL-10 in (chronic) active MS lesions. Most intense IL-4 immunoreactivity was detected in reactive fibrillary astrocytes within the hypocellular regions of chronic active and chronic inactive MS lesions. Strong immunoreactivity for IL-10R and IL-4R was detected on macrophages in both parenchymal and perivascular areas and on reactive astrocytes in active and chronic MS lesions. Our results indicate that IL-10 and IL-4 have an active role in CNS immune responses. The specific patterns of protein localization and protein expression for both IL-10 and IL-4 in MS lesions at different stages of development suggest that these anti-inflammatory cytokines and their receptors participate in processes leading to the formation of chronic MS lesions. GLIA 38:24,35, 2002. © 2002 Wiley-Liss, Inc. [source] Biochemical and molecular studies using human autopsy brain tissueJOURNAL OF NEUROCHEMISTRY, Issue 3 2003Matthew R. Hynd Abstract The use of human brain tissue obtained at autopsy for neurochemical, pharmacological and physiological analyses is reviewed. RNA and protein samples have been found suitable for expression profiling by techniques that include RT-PCR, cDNA microarrays, western blotting, immunohistochemistry and proteomics. The rapid development of molecular biological techniques has increased the impetus for this work to be applied to studies of brain disease. It has been shown that most nucleic acids and proteins are reasonably stable post-mortem. However, their abundance and integrity can exhibit marked intra- and intercase variability, making comparisons between case-groups difficult. Variability can reveal important functional and biochemical information. The correct interpretation of neurochemical data must take into account such factors as age, gender, ethnicity, medicative history, immediate ante-mortem status, agonal state and post-mortem and post-autopsy intervals. Here we consider issues associated with the sampling of DNA, RNA and proteins using human autopsy brain tissue in relation to various ante- and post-mortem factors. We conclude that valid and practical measures of a variety of parameters may be made in human brain tissue, provided that specific factors are controlled. [source] Expression of plasminogen activator inhibitor-1 and protease nexin-1 in human astrocytes: Response to injury-related factorsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 11 2010Karin Hultman Abstract Astrocytes play a diverse role in central nervous system (CNS) injury. Production of the serine protease inhibitors (serpins) plasminogen activator inhibitor-1 (PAI-1) and protease nexin-1 (PN-1) by astrocytes may counterbalance excessive serine protease activity associated with CNS pathologies such as ischemic stroke. Knowledge regarding the regulation of these genes in the brain is limited, so the objective of the present study was to characterize the effects of injury-related factors on serpin expression in human astrocytes. Native human astrocytes were exposed to hypoxia or cytokines, including interleukin-6 (IL-6), IL-1,, tumor necrosis factor-, (TNF-,), IL-10, transforming growth factor-, (TGF-,), and TGF-, for 0,20 hr. Serpin mRNA expression and protein secretion were determined by real-time RT-PCR and ELISA, respectively. Localization of PAI-1 and PN-1 in human brain tissue was examined by immunohistochemistry. Hypoxia and all assayed cytokines induced a significant increase in PAI-1 expression, whereas prolonged treatment with IL-1, or TNF-, resulted in a significant down-regulation. The most pronounced induction of both PAI-1 and PN-1 was observed following early treatment with TGF-,. In contrast to PAI-1, the PN-1 gene did not respond to hypoxia. Positive immunoreactivity for PAI-1 in human brain tissue was demonstrated in reactive astrocytes within gliotic areas of temporal cortex. We show here that human astrocytes express PAI-1 and PN-1 and demonstrate that this astrocytic expression is regulated in a dynamic manner by injury-related factors. © 2010 Wiley-Liss, Inc. [source] Island clustering analysis for the comparison of the membrane and the soluble protein fractions of human brain proteomePROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 6 2008Kyung-Hoon Kwon Abstract A protein identified in multiple separate bands of a 1-D gel reflects variation in the molecular weight caused by alternative splicing, endoproteolytic cleavage, or PTMs, such as glycosylation or ubiquitination. To characterize such a protein distribution over the bands, we defined an entity called an ,island' as the band region including the bands of the same protein identified sequentially. We quantified the island distribution using a new variable called an Iscore. Previously, as described in Park et al.. (Proteomics 2006, 6, 4978,4986.), we analyzed human brain tissue using a multidimensional MS/MS separation method. Here, the new method of island analysis was applied to the previous proteome data. The soluble and membrane protein fractions of human brain tissue were reanalyzed using the island distribution. The proteome of the soluble fraction exhibited more variation in island positions than that of the membrane fraction. Through the island analysis, we identified protein modifications and protein complexes over the 1-D gel bands. [source] Comparative cellular distribution of GABAA and GABAB receptors in the human basal ganglia: Immunohistochemical colocalization of the ,1 subunit of the GABAA receptor, and the GABABR1 and GABABR2 receptor subunitsTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2004Henry J. Waldvogel Abstract The GABAB receptor is a G-protein linked metabotropic receptor that is comprised of two major subunits, GABABR1 and GABABR2. In this study, the cellular distribution of the GABABR1 and GABABR2 subunits was investigated in the normal human basal ganglia using single and double immunohistochemical labeling techniques on fixed human brain tissue. The results showed that the GABAB receptor subunits GABABR1 and GABABR2 were both found on the same neurons and followed the same distribution patterns. In the striatum, these subunits were found on the five major types of interneurons based on morphology and neurochemical labeling (types 1, 2, 3, 5, 6) and showed weak labeling on the projection neurons (type 4). In the globus pallidus, intense GABABR1 and GABABR2 subunit labeling was found in large pallidal neurons, and in the substantia nigra, both pars compacta and pars reticulata neurons were labeled for both receptor subunits. Studies investigating the colocalization of the GABAA ,1 subunit and GABAB receptor subunits showed that the GABAA receptor ,1 subunit and the GABABR1 subunit were found together on GABAergic striatal interneurons (type 1 parvalbumin, type 2 calretinin, and type 3 GAD neurons) and on neurons in the globus pallidus and substantia nigra pars reticulata. GABABR1 and GABABR2 were found on substantia nigra pars compacta neurons but the GABAA receptor ,1 subunit was absent from these neurons. The results of this study provide the morphological basis for GABAergic transmission within the human basal ganglia and provides evidence that GABA acts through both GABAA and GABAB receptors. That is, GABA acts through GABAB receptors, which are located on most of the cell types of the striatum, globus pallidus, and substantia nigra. GABA also acts through GABAA receptors containing the ,1 subunit on specific striatal GABAergic interneurons and on output neurons of the globus pallidus and substantia nigra pars reticulata. J. Comp. Neurol. 470:339,356, 2004. © 2004 Wiley-Liss, Inc. [source] Dopamine Transporter in vitro Binding and in vivo Imaging in the BrainBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2001Kim A. Bergström Recent findings indicate that dopamine reuptake is more like a highly regulated than a constitutive determinant of dopamine clearance. Positron emission tomography (PET) and single-photon emission tomography (SPET) offer unique methods to study dopamine transporter function. Results from in vivo PET and SPET studies correspond well with in vitro studies performed on post mortem human brain tissue. Considering some of the variances between in vitro and in vivo receptor binding phenomena it may be that the role of a compound to alter binding to monoamine uptake sites in vitro does not indicate its potential to affect monoamine transporters after administration in vivo. This discrepancy may be better understood taking into account recent studies indicating the possibility of a rapid regulation of transporter function and surface expression. Furthermore, the dopamine transporter is a fruitful target for CNS drug discovery. Fundamental nature of drug actions in vivo may be studied using demonstrated in vitro and in vivo imaging methods. [source] Oligomeric A, in Alzheimer's Disease: Relationship to Plaque and Tangle Pathology, APOE Genotype and Cerebral Amyloid AngiopathyBRAIN PATHOLOGY, Issue 2 2010Zoë Van Helmond Abstract Despite accumulating evidence of a central role for oligomeric amyloid , (A,) in the pathogenesis of Alzheimer's Disease (AD), there is scant information on the relationship between the levels and distribution of oligomeric A, and those of other neurodegenerative abnormalities in AD. In the present study, we have found oligomeric A, to be associated with both diffuse and neuritic plaques (mostly co-localized with A,1,42) and with cerebrovascular deposits of A, in paraffin sections of formalin-fixed human brain tissue. The amount of oligomeric A, that was labeled in the sections correlated with total A, plaque load, but not phospho-tau load, cerebral amyloid angiopathy (CAA) severity or APOE genotype. Although soluble, oligomeric and insoluble A, levels were all significantly increased in AD brain homogenates, case-to-case variation and overlap between AD and controls were considerable. Over the age-range studied (43,98 years), the levels of soluble A,, oligomeric A,42, oligomeric A,40 and insoluble A, did not vary significantly with age. Oligomeric A,1,42 and insoluble A, levels were significantly higher in women. Overall, the level of insoluble A,, but neither oligomeric nor soluble A,, was associated with Braak stage, CAA severity and APOE,4 frequency, raising questions as to the role of soluble and oligomeric A, in the progression of AD. [source] Neuroproteomics and its applications in research on nicotine and other drugs of abusePROTEOMICS - CLINICAL APPLICATIONS, Issue 11 2007Ming D. Li Dr. Abstract The rapidly growing field of neuroproteomics is able to track changes in protein expression and protein modifications underlying various physiological conditions, including the neural diseases related to drug addiction. Thus, it presents great promise in characterizing protein function, biochemical pathways, and networks to understand the mechanisms underlying drug dependence. In this article, we first provide an overview of proteomics technologies and bioinformatics tools available to analyze proteomics data. Then we summarize the recent applications of proteomics to profile the protein expression pattern in animal or human brain tissues after the administration of nicotine, alcohol, amphetamine, butorphanol, cocaine, and morphine. By comparing the protein expression profiles in response to chronic nicotine exposure with those appearing in response to treatment with other drugs of abuse, we identified three biological processes that appears to be regulated by multiple drugs of abuse: energy metabolism, oxidative stress response, and protein degradation and modification. Such similarity indicates that despite the obvious differences among their chemical properties and the receptors with which they interact, different substances of abuse may cause some similar changes in cellular activities and biological processes in neurons. [source] Biomarker discovery: A proteomic approach for brain cancer profilingCANCER SCIENCE, Issue 2 2007Ashraf A. Khalil Gliomas in the form of astrocytomas, anaplastic astrocytomas and glioblastomas are the most common brain tumors in humans. Early detection of these cancers is crucial for successful treatment. Proteomics promises the discovery of biomarkers and tumor markers for early detection and diagnosis. In the current study, a differential gel electrophoresis technology coupled with matrix-assisted laser desorption/ionization,time of flight and liquid chromatography,tandem mass spectroscopy was used to investigate tumor-specific changes in the proteome of human brain cancer. Fifty human brain tissues comprising varying diagnostic groups (non-tumor, grade I, grade II, grade III and grade IV) were run in duplicate together with an internal pool sample on each gel. The proteins of interest were automatically picked, in-gel digested and mass spectrometry fingerprinted. Two hundred and eleven protein spots were identified successfully and were collapsed into 91 unique proteins. Approximately 20 of those 91 unique proteins had, to our knowledge, not been reported previously as differentially expressed in human brain cancer. Alb protein, peroxiredoxin 4 and SH3 domain-binding glutamic acid-rich-like protein 3 were upregulated in glioblastoma multiform versus non-tumor tissues. However, aldolase C fructose-biphosphate, creatine kinase, B chain dihydrolipoyl dehydrogenase, enolase 2, fumarate hydratase, HSP60, lactoylglutathione lyase, lucine aminopeptidase, Mu-crystallin homolog, NADH-UO 24, neurofilament triplet L protein, septin 2, stathmin and vacuolar ATP synthase subunit E were downregulated in glioblastoma multiform compared with non-tumor tissues. These differentially expressed proteins provided novel information on the differences existing between normal brain and gliomas, and thus might prove to be useful molecular indicators of diagnostic or prognostic value. (Cancer Sci 2007; 98: 201,213) [source] | |||||||||||||