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Brain Only (brain + only)
Selected AbstractsStage-specific gene expression in early differentiating oligodendrocytesGLIA, Issue 2 2002Francesca Blasi Abstract The screening of a differential library from precursor and differentiated oligodendrocytes, obtained through the representational difference analysis (RDA) technique, has generated a number of cDNA recombinants corresponding to mRNA coding for known and unknown proteins: (1) mRNA coding for proteins involved in protein synthesis, (2) mRNA coding for proteins involved in the organization of the cytoskeleton, and (3) mRNA coding for proteins of unknown function. The expression profile of the mRNA was studied by Northern blot hybridization to the poly-A+ mRNA from primary rat progenitor and differentiated oligodendrocytes. In most cases, hybridization to the precursor was higher than hybridization to the differentiated mRNA, supporting the validity of the differential screening. Hybridization of the cDNA to rat cerebral hemisphere and brain stem poly-A+ mRNA, isolated from 1- to 90-day-old rats, confirms the results obtained with the mRNA from differentiating oligodendrocytes. The intensity of the hybridization bands decreases as differentiation proceeds. The pattern of expression observed in oligodendrocytes is different from that found in the brain only in the case of the nexin-1 mRNA, the level of which remains essentially constant throughout differentiation both in the brain stem and in the cerebral hemispheres, in agreement with the published data. In contrast, the intensity of hybridization to the oligodendrocyte mRNA is dramatically lower in the differentiated cells compared with the progenitor oligodendrocyte cells. Some of the recombinant cDNA represent mRNA sequences present at high frequency distribution in the cells, while others belong to the rare sequences group. Six recombinants code for proteins of the ribosomal family, suggesting that of approximately 70 known ribosomal proteins, only a few are upregulated during oligodendrocyte differentiation. The third category of open reading frame (ORF) is represented by rare messengers coding for proteins of unknown functions and includes six clones: RDA 279, 11, 95, 96, 254, and 288. GLIA 39:114,123, 2002. © 2002 Wiley-Liss, Inc. [source] Pharmacokinetics and tissue distribution of idarubicin-loaded solid lipid nanoparticles after duodenal administration to ratsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2002Gian Paolo Zara Abstract Idarubicin-loaded solid lipid nanoparticles (IDA-SLN) and idarubicin in solution were prepared and the two formulations were administered to rats, either by the duodenal route or intravenously (iv). The aim of this research was to study whether the bioavailability of idarubicin can be improved by administering IDA-SLN duodenally to rats. Idarubicin and its main metabolite idarubicinol were determined in plasma and tissues by reversed-phase high-performance liquid chromatography. The pharmacokinetic parameters of idarubicin found after duodenal administration of the two formulations were different: area under the curve of concentration versus time (AUC) and elimination half-life were ,21 times and 30 times, respectively, higher after IDA-SLN administration than after the solution administration. Tissue distribution also differed: idarubicin and idarubicinol concentrations were lower in heart, lung, spleen, and kidneys after IDA-SLN administration than after solution administration. The drug and its metabolite were detected in the brain only after IDA-SLN administration, indicating that SLN were able to pass the blood,brain barrier. After iv IDA-SLN administration, the AUC of idarubicin was lower than after duodenal administration of the same formulation. Duodenal administration of IDA-SLN modifies the pharmacokinetics and tissue distribution of idarubicin. The IDA-SLN act as a prolonged release system for the drug. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1324,1333, 2002 [source] Neuroprotective effects of an immunosuppressant agent on diffusion/perfusion mismatch in transient focal ischemiaMAGNETIC RESONANCE IN MEDICINE, Issue 6 2004Toshihiko Ebisu Abstract The immunosuppressant FK506 (tacrolimus) exerts potent neuroprotection following focal ischemia in animals; however, the separate effects of FK506 on the ischemic core and penumbra have not been reported. The ischemic penumbra is clinically defined as the difference between a large abnormal area on perfusion-weighted imaging (PWI) and a smaller lesion on diffusion-weighted imaging (DWI). The goal of this study was to determine the effect of FK506 on DWI/PWI match and mismatch areas in transient focal ischemia in rats. Twelve rats were subjected to 1 hr of transient middle cerebral artery (MCA) occlusion, and given an intravenous injection of a placebo (N = 6) or 1 mg/kg FK506 (N = 6) immediately before reperfusion. Magnetic resonance imaging (MRI) was performed during MCA occlusion, and 0.5, 1, and 24 hr after reperfusion. FK506 significantly protected the ischemic brain only in the mismatch cortex where the initial apparent diffusion coefficient (ADC) was normal and there was a mild reduction of cerebral blood flow (CBF). This is the first report to describe the protective effects of FK506 on ischemic penumbra, as measured by DWI/PWI mismatch. The findings provide direct evidence for the utility of DWI/PWI mismatch as a guideline for therapeutic intervention with FK506. Magn Reson Med 51:1173,1180, 2004. © 2004 Wiley-Liss, Inc. [source] Piracetam improves mitochondrial dysfunction following oxidative stressBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2006Uta Keil Mitochondrial dysfunction including decrease of mitochondrial membrane potential and reduced ATP production represents a common final pathway of many conditions associated with oxidative stress, for example, hypoxia, hypoglycemia, and aging. Since the cognition-improving effects of the standard nootropic piracetam are usually more pronounced under such pathological conditions and young healthy animals usually benefit little by piracetam, the effect of piracetam on mitochondrial dysfunction following oxidative stress was investigated using PC12 cells and dissociated brain cells of animals treated with piracetam. Piracetam treatment at concentrations between 100 and 1000 ,M improved mitochondrial membrane potential and ATP production of PC12 cells following oxidative stress induced by sodium nitroprusside (SNP) and serum deprivation. Under conditions of mild serum deprivation, piracetam (500 ,M) induced a nearly complete recovery of mitochondrial membrane potential and ATP levels. Piracetam also reduced caspase 9 activity after SNP treatment. Piracetam treatment (100,500 mg kg,1 daily) of mice was also associated with improved mitochondrial function in dissociated brain cells. Significant improvement was mainly seen in aged animals and only less in young animals. Moreover, the same treatment reduced antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in aged mouse brain only, which are elevated as an adaptive response to the increased oxidative stress with aging. In conclusion, therapeutically relevant in vitro and in vivo concentrations of piracetam are able to improve mitochondrial dysfunction associated with oxidative stress and/or aging. Mitochondrial stabilization and protection might be an important mechanism to explain many of piracetam's beneficial effects in elderly patients. British Journal of Pharmacology (2006) 147, 199,208. doi:10.1038/sj.bjp.0706459 [source] II,Naomi Eilan ON THE ROLE OF PERCEPTUAL CONSCIOUSNESS IN EXPLAINING THE GOALS AND MECHANISMS OF VISION: A CONVERGENCE ON ATTENTION?ARISTOTELIAN SOCIETY SUPPLEMENTARY VOLUME, Issue 1 2006Naomi Eilan ABSTRACT The strong sensorimotor account of perception gives self-induced movements two constitutive roles in explaining visual consciousness. The first says that self-induced movements are vehicles of visual awareness, and for this reason consciousness ,does not happen in the brain only'. The second says that the phenomenal nature of visual experiences is consists in the action-directing content of vision. In response I suggest, first, that the sense in which visual awareness is active should be explained by appeal to the role of attention in visual consciousness, rather than self-induced movements; and second, that the sense in which perceptual consciousness does not happen in the brain only should be explained by appeal to the relational nature of perceptual consciousness, appeal to which also shows why links with action cannot exhaust phenomenal content. [source] Von Neuronen zu Netzwerken.BIOLOGIE IN UNSERER ZEIT (BIUZ), Issue 6 2009Mathematische Gehirnmodelle Abstract Obwohl unser Verständnis des Nervensystems große Fortschritte macht, stellen Netzwerke aus Milliarden von Neuronen die Neurobiologie vor eine praktisch unlösbare Aufgabe: Die Aktivität eines Gehirns möglichst vollständig zu erfassen und das Beobachtete detailliert zu verstehen. Die "Computational Neuroscience" versucht Brücken zwischen den Konzepten der Teildisziplinen zu schlagen. Die mathematische Beschreibung von Nervenzellen und neuronalen Netzwerken, sowie die Simulation dieser Systeme in Form von Computermodellen, erlaubt Phänomene zu ergründen, die in biologischen Gehirnen nur unter größten Schwierigkeiten messbar sind. Jüngste Studien konnten unter anderem zeigen, dass erregungsabhängige Veränderungen der elektrischen Leitfähigkeit in Neuronen ein Netzwerk davor bewahren, dass räumlich begrenzte Erregung sich aufschaukelt und als Folge die Aktivität im gesamten Netzwerk zum Erliegen bringt. Dieselbe Eigenschaft führt außerdem dazu, dass ein Netzwerk auch ohne äußere Anregung aktiv bleiben kann , eine wichtige Grundeigenschaft von Gehirnen, deren neuronale Funktionsmechanismen bis heute weitgehend unverstanden sind. Our understanding of the nervous system has made great leaps forward. Yet still, the study of networks of billions of neurons poses an almost insolvable challenge to empirical neurobiology: to capture the activity of a brain as a whole, and to make sense of the observations in detail. Here, "Computational Neuroscience" attempts to build bridges between the concepts of the involved disciplines. The mathematical description of neurons and neuronal networks, as well as the simulation of these systems as computer models, allows fathoming phenomena that could be measured in biological brains only under severe difficulties. In particular, recent studies showed that activity dependent changes of neuronal input resistance can prevent a network from local "explosions" of activity, which otherwise could lead to a complete breakdown of network operation. The same property of neurons also causes a network to remain active when external excitation is switched off. This is an important property of brains, the neuronal mechanisms of which are still widely unknown. 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