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Neural stem cells (NSCs) are maintained in the adult mammalian brain throughout the animal's lifespan. NSCs in the subependymal zone infrequently divide and generate transit amplifying cells, which are destined to become olfactory bulb neurons. When transit amplifying cells are depleted, they are replenished by the quiescent NSC pool. However, the cellular basis for this recovery process remains largely unknown. In this study, we traced NSCs and their progeny after transit amplifying cells were eliminated by intraventricular infusion of cytosine [beta]-D-arabinofuranoside. We found that although the number of neurosphere-forming NSCs decreased shortly after the treatment, they were restored to normal levels 3 weeks after the cessation of treatment. More importantly, the depletion of transit amplifying cells did not induce a significant expansion of the NSC pool by symmetric divisions. Our data suggest that the size of the NSC pool is hardly affected by brain damage due to antimitotic drug treatment. Keywords: Lentiviral barcoding, Clonal analysis, Subependymal zone, Neurospheres, Transit amplifying cell, Ara-C, Author(s): Zakiyyah Munirah Mohd Zaki[sup.1], Anri Kuroda[sup.1,2], Naoko Morimura[sup.1], Yoshitaka Hayashi[sup.1] and Seiji Hitoshi[sup.1] Background Quiescent neural stem cells (NSCs) are present in the subependymal zone (SEZ) of the postnatal [...]

Pyrazoles represent a significant class of heterocyclic compounds that exhibit pharmacological properties. The present study aimed to investigate the antioxidant potential of pyrazol derivative compounds in brain of mice in vitro and the effect of pyrazol derivative compounds in the oxidative damage and toxicity parameters in mouse brain and plasma of mice. The compounds tested were 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazol (1a), 3,5-dimethyl-4-(phenylselanyl)-1H-pyrazole (2a), 4-((4-methoxyphenyl)selanyl)-3,5-dimethyl-1-phenyl-1H-pyrazole (3a), 4-((4- chlorophenyl)selanyl)-3, 5-dimethyl-1-phenyl-1H-pyrazole (4a), 3,5-dimethyl-1-phenyl-4-(phenylthio)-1H-pyrazole (1b), 3,5-dimethyl-4- (phenylthio)-1H-pyrazole (2b), 4-((4-methoxyphenyl)thio)-3,5-dimethyl1-phenyl-1H-pyrazole (3b), 4-((4-chlorophenyl)thio)-3,5-dimethyl-1-phenyl-1H-pyrazole (4b), and 3,5- dimethyl-1-phenyl-1H-pyrazole (1c). In vitro, 4-(arylcalcogenyl)-1H-pyrazoles, at low molecular range, reduced lipid peroxidation and reactive species in mouse brain homogenates. The compounds also presented ferric-reducing ability as well nitric oxide-scavenging activity. Especially compounds 1a, 1b, and 1c presented efficiency to 1,1-diphenyl-2-picryl-hydrazyl-scavenging activity. Compounds 1b and 1c presented 2,20 -azinobis(3-ethylbenzthiazoline-6- sulfonic acid)-scavenging activity. In vivo assays demonstrated that compounds 1a, 1b, and 1c (300 mg/kg, intragastric, a single administration) did not cause alteration in the of [delta]-aminolevulinic acid dehydratase activity, an enzyme that exhibits high sensibility to prooxidants situations, in the brain, liver, and kidney of mice. Compound 1c reduced per se the lipid peroxidation in liver and brain of mice. Toxicological assays demonstrate that compounds 1a, 1b, and 1c did not present toxicity in the aspartate aminotransferase, alanine aminotransferase, urea, and creatinine levels in the plasma. In conclusion, the results demonstrated the antioxidant action of pyrazol derivative compounds in in vitro assays. Furthermore, the results showed low toxicity of compounds in in vivo assays. Key words: antioxidant, organoselenium, oxidative stress, toxicity, pyrazoles. Les pyrazoles representent une importante classe de composes heterocycliques dotes de proprietes pharmacologiques. La presente etude portait sur le potentiel antioxydant de composes derives des pyrazoles dans le cerveau de souris in vitro et sur l'effet des composes derives des pyrazoles sur les parametres des dommages et de la toxicite lies a l'oxydation dans le cerveau et le plasma de souris. Les composes evalues etaient les suivants : 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazole (1a), 3,5-dimethyl-4-(phenylselanyl)-1H-pyrazole (2a), 4-((4-methoxyphenyl)selanyl)- 3,5-dimethyl-1-phenyl-1H-pyrazole (3a), 4-((4chlorophenyl)selanyl)-3,5-dimethyl- 1-phenyl-1H-pyrazole (4a), 3,5-dimethyl-1-phenyl-4-(phenylthio)-1H-pyrazole (1b), 3,5-dimethyl-4-(phenylthio)-1H-pyrazole (2b), 4-((4-methoxyphenyl)thio)-3,5- dimethyl-1-phenyl-1H-pyrazole (3b), 4-((4-chlorophenyl)thio)-3,5-dimethyl-1-phenyl-1H-pyrazole (4b) et 3,5-dimethyl-1-phenyl-1H-pyrazole (1c). In vitro, les 4- (arylcalcogenyl)1H-pyrazoles, dans des proportions moleculaires faibles, entrainaient une diminution des taux de peroxydation lipidique et de derives reactifs dans des homogenats de cerveaux de souris. Les composes presentaient aussi une capacite de reduction ferrique, ainsi que de piegeage de l'oxyde nitrique. En particulier, les composes 1a, 1b et 1c affichaient une activite de piegeage efficace du 1,1-diphenyl-2-picryl-hydrazyle. Les composes 1b et 1c affichaient une activite de piegeage du 2,20-azino-bis (3-ethylbenzthiazoline-6-acide sulfonique). Les epreuves in vivo ont montre que les composes 1a, 1b et 1c (a 300 mg/kg, avec administration unique par voie intragastrique) n'ont pas entraine de diminution de l'activite de la dehydratase de l'acide [delta]-aminolevulinique, une enzyme qui presente une sensibilite elevee en situation de pro-oxydation, dans le cerveau, le foie et les reins de souris. Le compose 1c entrainait intrinsequement une diminution de la peroxydation lipidique dans le cerveau et le foie de souris. Les epreuves toxicologiques montrent que les composes 1a, 1b et 1c ne presentent pas de toxicite quant a l'aspartate aminotransferase et a l'alanine aminotransferase ainsi qu'aux taux d'uree et de creatinine dans le plasma. En conclusion, les resultats ont montre l'activite antioxydante de composes derives des pyrazoles dans le cadre d'epreuves in vitro. En outre, les resultats ont montre la faible toxicite des composes dans le cadre d'epreuves in vivo. Mots-des : antioxydant, organoselenium, stress oxydatif, toxicite, pyrazoles., Introduction Pyrazole, a five-membered ring structure composed of three carbon atoms and two nitrogen atoms in adjacent positions (Fig. 1), is reported to possess a wide range of biological activities [...]

Purpose: Understanding the brain basis of language and cognitive outcomes is a major goal of aphasia research. Prior studies have not often considered the many ways that brain features can relate to behavioral outcomes or the mechanisms underlying these relationships. The purpose of this review article is to provide a new framework for understanding the ways that brain features may relate to language and cognitive outcomes from stroke. Method: Brain-behavior relationships that may be important for aphasia outcomes are organized into a taxonomy, including features of the lesion and features of brain tissue spared by the lesion. Features of spared brain tissue are categorized into those that change after stroke and those that do not. Features that change are further subdivided, and multiple mechanisms of brain change after stroke are discussed. Results: Features of the stroke, including size, location, and white matter damage, relate to many behavioral outcomes and likely account for most of the variance in outcomes. Features of the spared brain tissue that are unchanged by stroke, such as prior ischemic disease in the white matter, contribute to outcomes. Many different neurobiological and behavioral mechanisms may drive changes in the brain after stroke in association with behavioral recovery. Changes primarily driven by neurobiology are likely to occur in brain regions with a systematic relationship to the stroke distribution. Changes primarily driven by behavior are likely to occur in brain networks related to the behavior driving the change. Conclusions: Organizing the various hypothesized brain-behavior relationships according to this framework and considering the mechanisms that drive these relationships may help investigators develop specific experimental designs and more complete statistical models to explain language and cognitive abilities after stroke. Eight main recommendations for future research are provided. Presentation Video: https://doi.org/10.23641asha.10257578, Long-term aphasia outcomes vary substantially between individual stroke survivors, including differences in the profile of deficits and spared abilities, as well as in the severity of specific deficits (Kertesz & [...]

Traumatic brain injury (TBI) is complex pathology with numerous long-term debilitating symptoms associated with damage to the brain parenchyma. It is necessary to better understand TBI at the cellular and molecular level to mitigate organ-level dysfunction. In particular, there is a lack in understanding the interplay of injury mechanics and mechanobiological responses in brain cells. This study aimed to analyze such effects from high-rate mechanical injuries, through an in vitro injury model of primary mixed brain cell cultures. Neurons and astrocytes interact in the proper functioning of neural networks and are critical components in the injury response of the central nervous system. The goal of this study was to analyze expression of abundant structural and adhesion molecules expressed by neurons and astrocytes to understand how intra- and intercellular signaling may be compromised as a result of high-rate mechanical insult. Target expression was measured for p-actin, vinculin, p-tubulin, ezrin, connexin-43, and glial fibrillary acidic protein. Transient alterations in both neuron and astrocytespecific molecules occurred over the time course of 48 hours after insult. This has implications for compromised cell-cell communication and provides potential molecular targets for mechanobiological mechanisms associated with neuron and astrocyte dysfunction following high-rate mechanical insult. Keywords: injury, shock wave, astrocyte, neuron, signaling, reactivity, connexin-43, INTRODUCTION Traumatic brain injury (TBI) is defined broadly as the complex cellular and molecular sequelae caused by external physical force enacting damage on the brain tissue. TBI can present clinically [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.joep.2010.03.002 Byline: Martin Reimann (a), Antoine Bechara (a)(b) Keywords: Somatic marker hypothesis; Iowa Gambling Task; Neuroeconomics; Emotion; Decision-making Abstract: A great deal of contemporary decision research in economics, business, psychology, and neuroscience now accepts the idea that emotions play a significant role in decision-making. Almost 20years ago, insights from studies on brain lesion patients set the cornerstone for this stream of research and led to the formulation of the somatic marker hypothesis. Despite some debate, the somatic marker framework is still providing a unique neuroanatomical and cognitive framework that helps explain the role of emotion in decision-making. In this article, we review the neurological background, core mechanisms, and critiques of the somatic marker theory, put into perspective conceptually related approaches that link emotion to decision-making, and present an outlook for future neuroeconomics research. Author Affiliation: (a) University of Southern California, Department of Psychology/Brain & Creativity Institute, 3620 McClintock Avenue, Los Angeles, CA 90089, USA (b) McGill University, Department of Psychiatry and Desantels Faculty of Management, Montreal, Quebec H3A 2TS Article History: Received 19 May 2009; Revised 2 June 2009; Accepted 23 June 2009

Purpose There is, in European countries that conduct medical chart review of intensive care unit (ICU) deaths, no consensus on uniform criteria for defining a potential organ donor. Although the term is increasingly being used in recent literature, it is seldom defined in detail. We searched for criteria for determination of imminent brain death, which can be seen as a precursor for organ donation. Methods We organized meetings with representatives from the field of clinical neurology, neurotraumatology, intensive care medicine, transplantation medicine, clinical intensive care ethics, and organ procurement management. During these meetings, all possible criteria were discussed to identify a patient with a reasonable probability to become brain dead (imminent brain death). We focused on the practical usefulness of two validated coma scales (Glasgow Coma Scale and the FOUR Score), brain stem reflexes and respiration to define imminent brain death. Further we discussed criteria to determine irreversibility and futility in acute neurological conditions. Results A patient who fulfills the definition of imminent brain death is a mechanically ventilated deeply comatose patient, admitted to an ICU, with irreversible catastrophic brain damage of known origin. A condition of imminent brain death requires either a Glasgow Coma Score of 3 and the progressive absence of at least three out of six brain stem reflexes or a FOUR score of E.sub.0M.sub.0B.sub.0R.sub.0. Conclusion The definition of imminent brain death can be used as a point of departure for potential heart-beating organ donor recognition on the intensive care unit or retrospective medical chart analysis., Author(s): Yorick J. de Groot [sup.1], Nichon E. Jansen [sup.2], Jan Bakker [sup.1], Michael A. Kuiper [sup.3], Stan Aerdts [sup.4], Andrew I. R. Maas [sup.5], Eelco F. M. Wijdicks [sup.6], [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2010.06.020 Byline: Gizem Donmez (1), Diana Wang (1), Dena E. Cohen (1), Leonard Guarente (1) Keywords: MOLNEURO; HUMDISEASE; SIGNALING Abstract: A hallmark of Alzheimer's disease (AD) is the accumulation of plaques of A[beta] 1-40 and 1-42 peptides, which result from the sequential cleavage of APP by the [beta] and [gamma]-secretases. The production of A[beta] peptides is avoided by alternate cleavage of APP by the [alpha] and [gamma]-secretases. Here we show that production of [beta]-amyloid and plaques in a mouse model of AD are reduced by overexpressing the NAD-dependent deacetylase SIRT1 in brain, and are increased by knocking out SIRT1 in brain. SIRT1 directly activates the transcription of the gene encoding the [alpha]-secretase, ADAM10. SIRT1 deacetylates and coactivates the retinoic acid receptor [beta], a known regulator of ADAM10 transcription. ADAM10 activation by SIRT1 also induces the Notch pathway, which is known to repair neuronal damage in the brain. Our findings indicate SIRT1 activation is a viable strategy to combat AD and perhaps other neurodegenerative diseases. Author Affiliation: (1) Paul F. Glenn Laboratory and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Article History: Received 19 January 2010; Revised 12 March 2010; Accepted 10 June 2010 Article Note: (miscellaneous) Published: July 22, 2010

Objective There is still a lack of knowledge on the age-dependent relation between a reduction in cerebral perfusion pressure (CPP) and compromised brain perfusion leading to excessive transmitter release and brain damage cascades. The hypothesis is that an age-dependent lower threshold of cerebral blood flow (CBF) autoregulation determines the amount and time course of transmitter accumulation. Design and setting This was a prospective randomized, blinded animal study performed in a university laboratory involving eight newborn and 11 juvenile anesthetized pigs. Intervention Striatal dopamine, glutamate, glucose, and lactate were monitored by microdialysis. For CPP manipulation, the cisterna magna was infused with artificial cerebrospinal fluid to control intracranial pressure at the maintained arterial blood pressure (stepwise CPP decrease in 15-min stages to 50, 40, 30, and finally 0 mmHg). Measurements and main results Juvenile pigs showed a gradual decrease in CBF between 50 mmHg CPP (CPP-50) and 30 mmHg CPP (CPP-30), but a significant CBF reduction did not occur in newborn piglets until CPP-30 (P < 0.05). At CPP-30, brain oxidative metabolism was reduced only in juveniles, concomitantly with elevations in dopamine and glutamate levels (P < 0.05). In contrast, newborn piglets exhibited a delayed and blunted accumulated of transmitters and metabolites (P < 0.05). Conclusions The lower limit of CBF autoregulation was associated with modifications in neurochemical parameters that clearly occurred before brain oxidative metabolism was compromised. Early indicators for mild to moderate hypoperfusion are elevated levels of lactate and dopamine, but elevated levels of glutamate appear to be an indicator of brain ischemia. The shift to the left of the lower autoregulatory threshold is mainly responsible for the postponed neurochemical response to decrements in the CPP in the immature brain., Author(s): Bernd Walter [sup.1] [sup.2], Kristina Aisenpreis [sup.1], Harald G. Fritz [sup.3], Jens Soukup [sup.5], Michael Eiselt [sup.4], Reinhard Bauer [sup.1] Author Affiliations: (1) grid.9613.d, 0000000119392794, Institute of Molecular Cell [...]

Information about brain impairment and strategies for teachers to teach brain-impaired students are provided.