pinecone/core-2020-05-10-deduplication huggingface dataset:
Reducing Hemorrhagic Complication by Dabigatran Via Neurovascular Protection After Recanalization With Tissue Plasminogen Activator in Ischemic Stroke of Rat

This study assesses the risks and benefits of tissue plasminogen activator (tPA) treatment under oral anticoagulation with dabigatran compared with warfarin or vehicle control in transient middle cerebral artery occlusion (tMCAO). After pretreatment with warfarin (0.2 mg/kg/day), dabigatran (20 mg/kg/day), or vehicle (0.5% carboxymethyl cellulose sodium salt) for 7 days, tMCAO was induced for 120 min, followed by reperfusion and tPA (10 mg/kg/10 ml). Clinical parameters, including cerebral infarction volume, hemorrhagic volume, and blood coagulation, were examined. At 24 hr after reperfusion, markers for the neurovascular unit at the peri-ischemic lesion were immunohistochemically examined in brain sections, and MMP-9 activity was measured by zymography. Paraparesis and intracerebral hemorrhage volume were significantly improved in the dabigatran-pretreated group compared with the warfarin-pretreated group. A marked dissociation between astrocyte foot processes and the basal lamina or pericyte was observed in the warfarin-pretreated group, which was greatly improved in the dabigatran-pretreated group. Furthermore, a remarkable activation of MMP-9 in the ipsilateral warfarin-pretreated rat brain was greatly reduced in dabigatran-pretreated rats. The present study reveals that the mechanism of intracerebral hemorrhage with warfarin-pretreatment plus tPA in ischemic stroke rats is the dissociation of the neurovascular unit, including the pericyte. Neurovascular protection by dabigatran, which was first shown in this study, could partially explain the reduction in hemorrhagic complication by dabigatran reported from clinical study
Glucose pathways adaptation supports acquisition of activated microglia phenotype

With its capacity to survey the environment and phagocyte debris, microglia assume a diversity of phenotypes to respond specifically through neurotrophic and toxic effects. Although these roles are well accepted, the underlying energetic mechanisms associated with microglial activation remain largely unclear. This study investigates microglia metabolic adaptation to ATP, NADPH, H(+) , and reactive oxygen species production. To this end, in vitro studies were performed with BV-2 cells before and after activation with lipopolysaccharide + interferon-γ. Nitric oxide (NO) was measured as a marker of cell activation. Our results show that microglial activation triggers a metabolic reprogramming based on an increased glucose uptake and a strengthening of anaerobic glycolysis, as well as of the pentose pathway oxidative branch, while retaining the mitochondrial activity. Based on this energy commitment, microglial defense capacity increases rapidly as well as ribose-5-phosphate and nucleic acid formation for gene transcription, essential to ensure the newly acquired functions demanded by central nervous system signaling. We also review the role of NO in this microglial energy commitment that positions cytotoxic microglia within the energetics of the astrocyte-neuron lactate shuttle
Zinc transporters ZnT3 and ZnT6 are downregulated in the spinal cords of patients with sporadic amyotrophic lateral sclerosis

本文のみを公開。The loss of homeostasis of essential metals is associated with various diseases, including neurodegenerative diseases. Previous studies have shown that the levels of zinc (Zn) are significantly higher in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS). Zn transporters and metallothioneins tightly control intracellular and extracellular Zn levels. This study investigated the protein levels of ZnT, a Zn transporter family, in ALS patients and model mice. The mRNA expression of ZnT1, −3, −4, −5, −6, −7, and −10 was assessed in the spinal cords of human control subjects. ZnT3 and ZnT6 protein levels were significantly diminished in the spinal cords of sporadic ALS patients compared with controls. Furthermore, immunohistochemical staining demonstrated decreased ZnT3 and ZnT6 immunoreactivity in the ventral horn of the spinal cords in ALS patients. Moreover, immunohistochemical analysis revealed that all ZnTs expressed in the spinal cords were localized in a distinct subset of motor neurons. In addition, ZnT3 and ZnT6 protein levels were not altered in SOD1 (G93A) mutant transgenic mice before or after the onset of ALS symptoms compared with controls. These results suggest that ZnT3 and ZnT6 protein levels are decreased in the spinal cords of sporadic ALS patients; however, this did not occur merely via loss of motor neurons. © 2014 Wiley Periodicals, Inc
The Impact of Stress in Decision Making in the Context of Uncertainty

For a number of decades, different fields of knowledge, including psychology, economics, and neurosciences, have focused their research efforts on a better understanding of the decision-making process. Making decisions based on the probability of future events is routine in everyday life; it occurs whenever individuals select an option from several alternatives, each one associated with a specific value. Sometimes subjects decide knowing the precise outcomes of each option, but commonly they have to decide without knowing the consequences (because either ambiguity or risk is involved). Stress has a broad impact on animal behaviors, affects brain regions involved in decision-making processes, and, when maladaptive, is a trigger for neuropsychiatric disorders. This Mini-Review provides a comprehensive overview on how stress impacts decision-making processes, particularly under uncertain conditions. Understanding this can prove to be useful for intervention related to impairments to decision-making processes that present in several stress-triggered neuropsychiatric disorders.Foundation for Science and Technology . Grant Numbers: SFRH/SINTD/60129/2009 , PTDC/SAU-NSC/111814/2009;   Programa Operacional Factores de Competitividade (COMPETE)].info:eu-repo/semantics/publishedVersio
Temporal changes in neurotrophic factors and neurite outgrowth in the major pelvic ganglion following cavernous nerve injury

Despite nerve-sparing radical prostatectomy, nerve damage and erectile dysfunction (ED) prevail, and preventing neurodegeneration is of great importance. Neurotrophic factors and neurite outgrowth were characterized in major pelvic ganglia (MPG) following bilateral cavernous nerve injury (BCNI). Young male Sprague-Dawley rats underwent sham or BCNI surgery, and the intracavernosal pressure to mean arterial pressure ratio was measured 2, 7, 14, 21, 30, and 60 days following injury (nâ=â8/group). MPG gene expression (qPCR) and Western blot were performed for glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurturin, neurotrophin (NT)-3, NT4, brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor, and activating transcription factor 3 (ATF3). Additional rats were injured, and MPGs were removed 24 hr, 48 hr, 3 days, and 7 days following BCNI (nâ=â3/group). MPGs were cultured in Matrigel, and neurite outgrowth was measured. Erections were impaired early and improved by 60 days in BCNI rats. GDNF, NGF, BDNF, and ATF3 gene expression was significantly increased and NT3 was decreased in MPGs following BCNI (48 hr to 21 days, Pâ<â0.05). GDNF and NGF protein levels were elevated in 48-hr BCNI rats. MPG neurite outgrowth from 24-hr and 48-hr BCNI was higher than sham (658âÂ±â19 Î¼m, 607âÂ±â24 Î¼m, 393âÂ±â23 Î¼m, respectively, Pâ<â0.05). Further studies examining the roles of neurotrophic factors in modulating signaling pathways may provide therapeutic avenues for neurogenically mediated ED. Â© 2015 Wiley Periodicals, Inc.status: publishe
Do cortical plasticity mechanisms differ between males and females?

The difference between male and female behavior and male and female susceptibility to a number of neuropsychiatric conditions is not controversial. From a biological perspective, one might expect to see at least some of these differences underpinned by identifiable physical differences in the brain. This Mini-Review focuses on evidence that plasticity mechanisms differ between males and females and ask at what scale of organization the differences might exist, at the systems level, the circuits level, or the synaptic level. Emerging evidence suggests that plasticity differences may extend to the scale of synaptic mechanisms. In particular, the CaMKK, NOS1 and estrogen receptor pathways show sexual dimorphisms with implications for plasticity in the hippocampus and cerebral cortex
Why sex hormones matter for neuroscience : a very short review on sex, sex hormones, and functional brain asymmetries.

Biological sex and sex hormones are known to affect functional cerebral asymmetries (FCAs). Men are generally more lateralized than women. The effect size of this sex difference is small but robust. Some of the inconsistencies in the literature may be explained by sex-related hormonal differences. Most studies focusing on neuromodulatory properties of sex hormones on FCAs have investigated women during the menstrual cycle. Although contradictions exist, these studies have typically shown that levels of estradiol and/or progesterone correlate with the degree of FCAs, suggesting that sex differences in FCAs partially depend on hormonal state and day of testing. The results indicate that FCAs are not fixed but are hormone dependent, and as such they can dynamically change within relatively short periods throughout life. Many issues raised in this Mini-Review refer not only to FCAs but also to other aspects of functional brain organization, such as functional connectivity within and between the cerebral hemispheres. Our understanding of sex differences in brain and behavior as well as their clinical relevance will improve significantly if more studies routinely take sex and sex hormones into account
Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a chronic, progressive disorder of the central nervous system (CNS) that affects more than two million people worldwide. Several animal models resemble MS pathology; the most employed are experimental autoimmune encephalomyelitis (EAE) and toxin- and/or virus-induced demyelination. In this review we will summarize our knowledge on the utility of different animal models in MS research. Although animal models cannot replicate the complexity and heterogeneity of the MS pathology, they have proved to be useful for the development of several drugs approved for treatment of MS patients. This review focuses on EAE because it represents both clinical and pathological features of MS. During the past decades, EAE has been effective in illuminating various pathological processes that occur during MS, including inflammation, CNS penetration, demyelination, axonopathy, and neuron loss mediated by immune cells."This is the peer reviewed version of the following article: Bjelobaba I, Begovic-Kupresanin V, Pekovic S, Lavrnja I. Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis. J Neurosci Res. 2018, which has been published in final form at [https://doi.org/10.1002/jnr.24224]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Isolation, characterization, and substrate properties of the external limiting membrane from the avian embryonic optic tectum

The external limiting membrane of the avian embryonic optic tectum is isolated by mechanically separating the neuronal mesencephalon from the overlying mesenchymal tissue. The preparation consists of a basal lamina which is covered on its neural side by endfeet of neuroepithelial cells and has attached to it on its meningeal side a collageneous stroma, containing blood vessels. The external limiting membrane can be flat-mounted on a piece of nitrocellulose filter as mechanical support. It covers an area between 0.3 and 1 the cm2, depending on the age of me donor embryo. The endfeet can be removed together with all cellular components of the meninges by treatment with 2% Triton-X-100 or with distilled water. The basal lamina itself is approximately 80 nm thick and consists of two laminae rarae and a central lamina densa. Immunohistochemical staining reveals that the basal lamina in the embryo, after isolation and after detergent extraction of the isolated preparation, contains type IV collagen, nidogen, laminin, and low density heparan sulfate proteoglycan as do other basement membranes. Antibodies against the neural cell adhesion molecule (N-CAM), chondroitin sulfate proteoglycan, and fibronectin fail to stain the external limiting membrane, but these proteins were clearly identified in the blood vessel-containing meninges or in the optic tectum. 
The flat-mounted external limiting membrane preparation was used as substrate to culture several different neural tissues of central and peripheral origin. Explants of neural crest cells, dorsal root ganglia, and sympathetic ganglia can be cultured on the external limiting membrane. All explants grow well on the basal lamina preparations whether the endfeet are attached or detergent-extracted prior to explantation; however, neurite outgrowth from sympathetic ganglia is reduced in the presence of the endfeet. Although the endfoot-lined external limiting membrane represents at least part of the immediate environment encountered by retinal axons as they invade the optic tectum and despite its excellent properties as a substrate for retinal axons in vitro, cues guiding the orientation of axons were not detected in the flat-mounted preparation.
Growth control of cultured microglia

Microglia, the resident macrophages of the brain, typically react to injuries or chronic diseases with proliferation and expression of differentiated features, such as production of cytokines associated with inflammatory events. Regulation and control of microglial cytokine expression, therefore, is a major focus of scientific interest. It has been shown that GMCSF and Il-3 are potent mitogens for microglia. Moreover, Il-3 and other cytokines are products of microglia. It is shown here that interleukin-1 (Il-1) as well as tumor necrosis factor (TNF alpha) increased microglial proliferation in mixed astrocyte-microglial cultures but had no mitogenic effects on isolated microglia. Lipopolysaccharide (LPS), the bacterial endotoxin, irreversibly inhibited microglial cell division in both mixed astrocyte-microglial cultures and in isolated microglial cultures. By contrast, the corticosteroids hydrocortisone and aldosterone and the synthetic glucocorticoid dexamethasone reversibly inhibited microglial proliferation. They also antagonized the stimulatory effects of Il-3 and granulocyte macrophage colony-stimulating factor (GMCSF). Estradiol and progesterone had no significant effects on mixed cultures but inhibited microglial proliferation in isolated cultures. Conditioned media from mixed cultures, isolated cultures, from the WEHI-2B cell line, or from fresh (serum-supplemented) media stimulated microglial proliferation to various extents. In summary, cytokine-mediated microglial proliferation can be down-regulated by a variety of steroid hormones. Along with their unimpaired access to brain cells in general, corticosteroids likely maintain an inhibitory tonus on microglial proliferation. It is hypothesized that this inhibition is overcome locally and temporally in brain injury and repair
Prognostic significance of nonsustained ventricular tachycardia in patients receiving cardiac resynchronization therapy for primary prevention: Analysis of the Japan cardiac device treatment registry database

BackgroundWhether nonsustained ventricular tachycardia (NSVT) is a marker of increased risk of sustained ventricular tachyarrhythmias (VTAs) remains to be established in patients receiving cardiac resynchronization therapy with a defibrillator (CRT‐D) for primary prevention.MethodsAmong the follow‐up data of the Japan cardiac device treatment registry (JCDTR) with an implantation date between January 2011 and August 2015, information regarding a history of NSVT before the CRT‐D implantation for primary prevention had been registered in 269 patients. Outcomes were compared between two groups with and without NSVT: NSVT group (n = 179) and No NSVT group (n = 90).ResultsThere was no significant difference with regard to age, gender, and NYHA class between the two groups. Left ventricular ejection fraction (LVEF) was 25.6% in the NSVT group and 28.0% in the No NSVT group (P = .046). The rate of appropriate therapy at 24 months was 26.0% and 18.4% in the NSVT and No NSVT groups (P = .22), respectively. Survival free from heart failure death was reduced in the NSVT group, as compared with the No NSVT group, with the rate of 90.2% vs 97.2% at 24 months (P = .030). A multivariate analysis identified a history of NSVT, anemia, and no use of angiotensin‐converting enzyme inhibitor (ACEI) or angiotensin‐receptor blocker (ARB) as predictors of heart failure death.ConclusionsNSVT appears to be a surrogate marker of severe heart failure rather than a substrate for subsequent sustained VTAs in patients with CRT‐D for primary prevention
Design and baseline characteristics of the Xarelto Post-Authorization Safety & Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS)

Background: The phase III Japanese Rivaroxaban Once‐Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (J‐ROCKET AF) showed that the rivaroxaban group had a lower event rate of intracranial bleeding than the warfarin group and that rivaroxaban was noninferior to warfarin for the principal safety outcome. However, safety and effectiveness data from unselected patients with AF in everyday clinical practice in Japan are lacking. Methods: The Xarelto Post‐Authorization Safety & Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS) is a real‐world, prospective, single‐arm, observational study mandated by the Japanese authority as postmarketing surveillance. XAPASS involves patients with nonvalvular AF prescribed rivaroxaban. The principal safety outcome is a composite of major and nonmajor bleeding events, and the primary effectiveness outcome is the incidence of ischemic stroke, hemorrhagic stroke, noncentral nervous system systemic embolism, and myocardial infarction. Results: n total, 11 308 patients were enrolled from April 2012 to June 2014. Their age was 73.1 ± 9.9 years, and their CHADS₂ score was 2.2 ± 1.3. Female patients, patients aged ≥75 years, patients with a body weight of ≤50 kg, and patients with a creatinine clearance of <50 mL/min constituted 38.1%, 48.7%, 19.5%, and 23.9% of all patients, respectively. Almost half (53.2%) of patients were prescribed other anticoagulants before starting rivaroxaban. Conclusions: Data from this study will supplement those from the J‐ROCKET AF and provide practical information for the optimal use of rivaroxaban for stroke prevention in Japanese patients with AF (Clinicaltrials.gov: NCT01582737)
When does centrality matter? Scientific productivity and the moderating role of research specialization and cross-community ties

The present study addresses the ongoing debate concerning academic scientific productivity. Specifically, given the increasing number of collaborations in academia and the crucial role networks play in knowledge creation, we investigate the extent to which building social capital within the academic community represents a valuable resource for a scientist's knowledge-creation process. We measure the social capital in terms of structural position within the academic collaborative network. Furthermore, we analyse the extent to which an academic scientist's research specialization and ties that cross-community boundaries act as moderators of the aforementioned relationship. Empirical results derived from an analysis of an Italian academic community from 2001 to 2008 suggest academic scientists that build social capital by occupying central positions in the community outperform their more isolated colleagues. However, scientific productivity declines beyond a certain threshold value of centrality, hence revealing the existence of an inverted U-shaped relationship. This relationship is negatively moderated by the extent to which an academic focuses research activities in few scientific knowledge domains, whereas it is positively moderated by the number of cross-community ties established
Reassessing the protean career concept: empirical findings, conceptual components, and measurement

This article was published in the serial Journal of Organizational Behavior [© John Wiley & Sons, Ltd.] The definitive version is available at: http://dx.doi.org/10.1002/job.1908The protean career concept is a widely acknowledged contemporary career model, but conceptual and empirical analysis of the model is scarce. We provide an integrative literature review of empirical research and note that the research is hampered by inconsistent use of terminology and methodological limitations. First, we show that the two protean metacompetencies-adaptability and identity-have been relatively neglected as the research has evolved. Second, we describe how preexisting protean measures are limited in covering the full range of the concept. Finally, we draw on career theory to suggest four conceptual components as a basis for future model development and offer suggestions for research that tests the utility of the protean career concept in relation to other similar constructs. © 2013 John Wiley & Sons, Ltd
Psychological capital: A review and synthesis

The concept of psychological capital (PsyCap) has attracted a great deal of interest from both academics and practitioners and has been linked to employee attitudes, behavior and performance at different levels of analysis. Yet, the nature of the concept, its measurement, the factors that influence its development, and when and how it influences individual-level, team-level and organizational-level outcomes are the subject of continued debate in the literature. This article offers a detailed and focused review of the existing literature on PsyCap, with the aim of developing an agenda for future research. In particular, we call for researchers to pay greater attention to possible multi-level applications of PsyCap research, examine the underlying mechanisms by which PsyCap influences individual-level, team-level and organizational-level outcomes, and identify possible factors that may moderate the relationship between PsyCap and its outcomes. In doing this, we provide a roadmap for scholars to progress the development of the field. &copy; 2014 John Wiley &amp; Sons, Ltd
A critique on neuroscientific methodologies in organizational behavior and management studies

Organizational neuroscience continues to flourish in organizational behavior and management studies as indicated by the growing number of publications. However, with a few exceptions, substantive critiques of organizational neuroscience are conspicuous by their absence. In this point-counterpoint article, we aim to redress this imbalance. We do so by asking two significant yet neglected questions: (i) how strong is the science behind this domain, and (ii) why are we doing this type of research (the so what? question)? Our analysis shows that the science behind  organizational neuroscience is far less rigorous than currently advocated (due to low statistical power of some neuroimaging studies plus an inability to locate mental  phenomena precisely in the brain). In terms of the so what? question, we  encourage researchers to move away from general statements and become more specific about the phenomena they research. We contend that the practical implications of this research, as well as inferences of the link to behavioral  changes, are currently overstated. We also underscore the importance for these studies to become contextually sensitive in order for the researchers to capture important events in the workplace. Finally, we offer some suggestions for future research.Full Tex