Endothelin ETB Receptor-Mediated Astrocytic Activation: Pathological Roles in Brain Disorders

In brain disorders, reactive astrocytes, which are characterized by hypertrophy of the cell body and proliferative properties, are commonly observed. As reactive astrocytes are involved in the pathogenesis of several brain disorders, the control of astrocytic function has been proposed as a therapeutic strategy, and target molecules to effectively control astrocytic functions have been investigated. The production of brain endothelin-1 (ET-1), which increases in brain disorders, is involved in the pathophysiological response of the nervous system. Endothelin B (ET_B) receptors are highly expressed in reactive astrocytes and are upregulated by brain injury. Activation of astrocyte ET_B receptors promotes the induction of reactive astrocytes. In addition, the production of various astrocyte-derived factors, including neurotrophic factors and vascular permeability regulators, is regulated by ET_B receptors. In animal models of Alzheimer’s disease, brain ischemia, neuropathic pain, and traumatic brain injury, ET_B-receptor-mediated regulation of astrocytic activation has been reported to improve brain disorders. Therefore, the astrocytic ET_B receptor is expected to be a promising drug target to improve several brain disorders. This article reviews the roles of ET_B receptors in astrocytic activation and discusses its possible applications in the treatment of brain disorders.     

A GIS-based management and publication framework for data handling of numerical model results

There has been an increasing awareness that large-scale datasets of earth-system model results would be produced and accumulated rapidly within the next few decades with extensive usage of numerical models. The successful exploration of these data for scientific research and engineering applications requires the capability of efficient storage, retrieval, integration and visualization of these large datasets. Robust publication methods are also needed to enable data exchange through the web to increase global research collaborations. In this study, a comprehensive GIS-based data management and publication framework (GMPF) was developed and applied to the use, representation, and analysis of hydrodynamic modeling results of Hamburg Port, Germany. Linking with GIS, a desktop- and a web-based model-results data atlas were developed to provide an interactive environment for various cartography and time series plots. The implementation of the framework was based on modular software design, open specifications and reuse of open source projects. The study results showed that the project life-cycle was shortened and development efforts were reduced through applying GMPF. The developed system could be integrated into commercial hydrodynamics software platforms to enhance the capability of model-results management and publication.     

Lactate as a Metabolite and a Regulator in the Central Nervous System

More than two hundred years after its discovery, lactate still remains an intriguing molecule. Considered for a long time as a waste product of metabolism and the culprit behind muscular fatigue, it was then recognized as an important fuel for many cells. In particular, in the nervous system, it has been proposed that lactate, released by astrocytes in response to neuronal activation, is taken up by neurons, oxidized to pyruvate and used for synthesizing acetyl-CoA to be used for the tricarboxylic acid cycle. More recently, in addition to this metabolic role, the discovery of a specific receptor prompted a reconsideration of its role, and lactate is now seen as a sort of hormone, even involved in processes as complex as memory formation and neuroprotection. As a matter of fact, exercise offers many benefits for our organisms, and seems to delay brain aging and neurodegeneration. Now, exercise induces the production and release of lactate into the blood which can reach the liver, the heart, and also the brain. Can lactate be a beneficial molecule produced during exercise, and offer neuroprotection? In this review, we summarize what we have known on lactate, discussing the roles that have been attributed to this molecule over time.     

An unsupervised learning method with a clustering approach for tumor identification and tissue segmentation in magnetic resonance brain images

Malignant and benign types of tumor infiltrated in human brain are diagnosed with the help of an MRI scanner. With the slice images obtained using an MRI scanner, certain image processing techniques are utilized to have a clear anatomy of brain tissues. One such image processing technique is hybrid self-organizing map (SOM) with fuzzy K means (FKM) algorithm, which offers successful identification of tumor and good segmentation of tissue regions present inside the tissues of brain. The proposed algorithm is efficient in terms of Jaccard Index, Dice Overlap Index (DOI), sensitivity, specificity, peak signal to noise ratio (PSNR), mean square error (MSE), computational time and memory requirement. The algorithm proposed through this paper has better data handling capacities and it also performs efficient processing upon the input magnetic resonance (MR) brain images. Automatic detection of tumor region in MR (magnetic resonance) brain images has a high impact in helping the radio surgeons assess the size of the tumor present inside the tissues of brain and it also supports in identifying the exact topographical location of tumor region. The proposed hybrid SOM-FKM algorithm assists the radio surgeon by providing an automated tissue segmentation and tumor identification, thus enhancing radio therapeutic procedures. The efficiency of the proposed technique is verified using the clinical images obtained from four patients, along with the images taken from Harvard Brain Repository.     

Tracking and characterizing the head motion of unanaesthetized rats in positron emission tomography

Positron emission tomography (PET) is an important in vivo molecular imaging technique for translational research. Imaging unanaesthetized rats using motion-compensated PET avoids the confounding impact of anaesthetic drugs and enables animals to be imaged during normal or evoked behaviour. However, there is little published data on the nature of rat head motion to inform the design of suitable marker-based motion-tracking set-ups for brain imaging—specifically, set-ups that afford close to uninterrupted tracking. We performed a systematic study of rat head motion parameters for unanaesthetized tube-bound and freely moving rats with a view to designing suitable motion-tracking set-ups in each case. For tube-bound rats, using a single appropriately placed binocular tracker, uninterrupted tracking was possible greater than 95 per cent of the time. For freely moving rats, simulations and measurements of a live subject indicated that two opposed binocular trackers are sufficient (less than 10% interruption to tracking) for a wide variety of behaviour types. We conclude that reliable tracking of head pose can be achieved with marker-based optical-motion-tracking systems for both tube-bound and freely moving rats undergoing PET studies without sedation.     

Energy conversion in woodpecker on successive peckings and its role on anti-shock protection of brain

To investigate the mechanism of brain protection of woodpecker, we built a finite element model of a whole woodpecker using computed topography scanning technique and geometry modeling. Dynamic analyses reveal: (i) 99.7% of the impact energy is converted into strain energy in the bulk of body and 0.3% is converted into strain energy in the head after three successive peckings, indicating the majority of the impact energy is stored in the bulk of body; (ii) the strain energy in brain is mainly converted into the dissipated energy, alleviating the mechanical injury to brain; (iii) the deformation and the effective energy dissipation of the beaks facilitate the decrease of the stress and impact energy transferred to the brain; (iv) the skull and dura mater not only provide the physical protection for the brain, but also diminish the strain energy in the brain by energy dissipation; (v) the binding of skull with the hyoid bone enhances the anti-shock ability of head. The whole body of the woodpecker gets involved in the energy conversion and forms an efficient anti-shock protection system for brain.     

Delivery of cefotaxime to the brain via intranasal administration

The purpose of this study was to investigate the plausibility of delivery of cefotaxime to the brain via intranasal administration. In vitro permeation studies were carried out using Franz diffusion cells, and the effect of different concentrations of chitosan (0.1% w/v and 0.25% w/v) on drug permeation across the bovine olfactory mucosa was determined. Samples were collected from the receiver compartment at different time points and analyzed using HPLC. The amount of cefotaxime that permeated across the olfactory mucosa when 0.25% w/v of chitosan was used as a permeation enhancer was ~1.5- and ~2-fold higher at the end of the first hour and second hour, respectively, over control (29.56?±?6.18 µg/cm²). There was no significant enhancement in drug permeation when 0.1% w/v chitosan was used as the permeation enhancer. Pharmacokinetic studies were carried out using Sprague-Dawley rats. Cefotaxime solution with 0.25% w/v chitosan (40?mg/kg) was administered intravenously (i.v.) to rats in groups 1 and 3 and intranasally to those in group 2 and 4. The time course of drug in the brain was investigated by performing microdialysis in rats of groups 1 and 2. Blood samples were withdrawn from rats in groups 3 and 4, and cefotaxime in plasma was analyzed using HPLC after extraction with a hydrochloric acid–chloroform:1-pentanol (3:1) and phosphate buffer solvent system. Pharmacokinetic parameters were calculated using the trapezoidal rule. The results imply that the drug levels attained in the brain following i.v. and intranasal administrations were comparable. These results suggest that intranasal administration of cefotaxime could be a potential method of delivering antibacterial agents because of it being noninvasive and patient compliant.     

Administration of xylo-oligosaccharides improves depressive-like behaviour in mice caused by chronic unpredictable mild stress by altering microbiota composition

Xylo-oligosaccharides (XOS) is a functional oligosaccharide with prebiotic properties, and could be fermented by gut microbiota. In this study, the modulatory effects of XOS on emotions and behaviours at different dose were investigated based on the mouse model of chronic unpredictable mild stress-induced depression. The result showed that 0.23 and 0.50 g kg⁻¹ doses of XOS significantly increased sucrose preference index and decreased the immobility time in tail suspension and forced swimming tests. Meanwhile, the dose of 0.23 g kg⁻¹ day⁻¹ XOS significantly increased the concentration of neurotransmitters, such as 5-hydroxytryptamine and γ- aminobutyric acid. Furthermore, the analysis of the faecal microbiota with XOS intervention showed a higher relative abundance of Akkermansia, Bifidobacterium and Lactobacillus, fewer Desulfovibrio and the SCFA concentrations increased with XOS prevention treatment. These results suggested that the dietary supplementation XOS could improve chronic stress-induced depressive-like behaviour by modulating neurotransmitters and reverting gut microbiota changes in mice. These findings present XOS as a potential prebiotic targeting to the gut microbiota for mood disorders.     

Ligand-Installed Nanocarriers toward Precision Therapy

Development of drug-delivery systems that selectively target neoplastic cells has been a major goal of nanomedicine. One major strategy for achieving this milestone is to install ligands on the surface of nanocarriers to enhance delivery to target tissues, as well as to enhance internalization of nanocarriers by target cells, which improves accuracy, efficacy, and ultimately enhances patient outcomes. Herein, recent advances regarding the development of ligand-installed nanocarriers are introduced and the effect of their design on biological performance is discussed. Besides academic achievements, progress on ligand-installed nanocarriers in clinical trials is presented, along with the challenges faced by these formulations. Lastly, the future perspectives of ligand-installed nanocarriers are discussed, with particular emphasis on their potential for emerging precision therapies.     

The Cut and the Continuum: Sophie Ristelhueber’s Anatomical Atlas

From her early photographs of the ruinous aftermath of the Lebanon War in Beirut (1982) to her more recent images of bomb craters in Eleven Blowups (2006), the French artist Sophie Ristelhueber has been intent to maintain, in her own metaphor, ‘the analytical distance of an anatomy lesson’. Exhibiting the evidence of warfare but withholding their explanation, Ristelhueber’s provocative gesture of making art of war, removing human conflicts from their political contexts to render them as still-lifes, ready-mades, earthworks, or surrealist poems, is patently anti-journalistic. In keeping with the artist’s surgical analogy, this article explores Ristelhueber’s aesthetic mode of address as one that shares its fundamental operation with that of photography – namely, to make a cut. Retracing the morphology of recurring imprints and injuries that appear across the terrestrial and corporeal expanses traversed in her work, the article considers the ways in which these cuts pertain to the transformative power of violence and images alike.