rudyvdbrink/CitationDatabase huggingface dataset:
Glutamate Increases In Vitro Survival and Proliferation and Attenuates Oxidative Stress-Induced Cell Death in Adult Spinal Cord-Derived Neural Stem/Progenitor Cells via Non-NMDA Ionotropic Glutamate Receptors.
Stem cells and development, 2016

Traumatic spinal cord injury (SCI) leads to a cascade of secondary chemical insults, including oxidative stress and glutamate excitotoxicity, which damage host neurons and glia. Transplantation of exogenous neural stem/progenitor cells (NSPCs) has shown promise in enhancing regeneration after SCI, although survival of transplanted cells remains poor. Understanding the response of NSPCs to the chemical mediators of secondary injury is essential in finding therapies to enhance survival. We examined the in vitro effects of glutamate and glutamate receptor agonists on adult rat spinal cord-derived NSPCs. NSPCs isolated from the periventricular region of the adult rat spinal cord were exposed to various concentrations of glutamate for 96 h. We found that glutamate treatment (500 μM) for 96 h significantly increased live cell numbers, reduced cell death, and increased proliferation, but did not significantly alter cell phenotype. Concurrent glutamate treatment (500 μM) in the setting of H2O2 exposure (500 μM) for 10 h increased NSPC survival compared to H2O2 exposure alone. The effects of glutamate on NSPCs were blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist GYKI-52466, but not by the N-methyl-D-aspartic acid receptor antagonist MK-801 or DL-AP5, or the mGluR3 antagonist LY-341495. Furthermore, treatment of NSPCs with AMPA, kainic acid, or the kainate receptor-specific agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid mimicked the responses seen with glutamate both alone and in the setting of oxidative stress. These findings offer important insights into potential mechanisms to enhance NSPC survival and implicate a potential role for glutamate in promoting NSPC survival and proliferation after traumatic SCI.
Analyses of thrombi in acute ischemic stroke: A consensus statement on current knowledge and future directions.
International journal of stroke : official journal of the International Stroke Society, 2017

Limited data exist on clot composition and detailed characteristics of arterial thrombi associated with large vessel occlusion in acute ischemic stroke. Advances in endovascular thrombectomy and related imaging modalities have created a unique opportunity to analyze thrombi removed from cerebral arteries. Insights into thrombus composition, etiology, physical properties and neurovascular interactions may lead to future advancements in acute ischemic stroke treatment and improved clinical outcomes. Advances in imaging techniques may enhance clot characterization and inform therapeutic decision-making prior to treatment and reveal stroke etiology to guide secondary prevention. Current imaging techniques can provide some information about thrombi, but there remains much to evaluate about relationships that may exist among thrombus composition, occlusion characteristics and treatment outcomes. Improved pathophysiological characterization of clot types, their properties and how these properties change over time, together with clinical correlates from ongoing studies, may facilitate revascularization with thrombolysis and thrombectomy. Interdisciplinary approaches covering clinical, engineering and scientific aspects of thrombus research will be key to advancing the understanding of thrombi and improving acute ischemic stroke therapy. This consensus statement integrates recent research on clots and thrombi retrieved from cerebral arteries and provides a rationale for further analyses, including current opportunities and limitations.
Critical role of neuropeptides B/W receptor 1 signaling in social behavior and fear memory.
PloS one, 2011

Neuropeptide B/W receptor 1 (NPBWR1) is a G-protein coupled receptor, which was initially reported as an orphan receptor, and whose ligands were identified by this and other groups in 2002 and 2003. To examine the physiological roles of NPBWR1, we examined phenotype of Npbwr1⁻/⁻ mice. When presented with an intruder mouse, Npbwr1⁻/⁻ mice showed impulsive contact with the strange mice, produced more intense approaches toward them, and had longer contact and chasing time along with greater and sustained elevation of heart rate and blood pressure compared to wild type mice. Npbwr1⁻/⁻ mice also showed increased autonomic and neuroendocrine responses to physical stress, suggesting that impairment of NPBWR1 leads to stress vulnerability. We also observed that these mice show abnormality in the contextual fear conditioning test. These data suggest that NPBWR1 plays a critical role in limbic system function and stress responses. Histological and electrophysiological studies showed that NPBWR1 acts as an inhibitory regulator on a subpopulation of GABAergic neurons in the lateral division of the CeA and terminates stress responses. These findings suggest important roles of NPBWR1 in regulating amygdala function during physical and social stress.
The relationship between cannabis use and cortisol levels in youth at ultra high-risk for psychosis.
Psychoneuroendocrinology, 2017

Recent studies have posited a relationship between cannabis use and the biological stress system, but this critical relationship has not been evaluated during the ultra high-risk (UHR) period immediately preceding the onset of psychotic disorders. Salivary cortisol samples were collected on 46 UHR and 29 control adolescents; these individuals were assessed for current cannabis use with a urine panel and self-report. UHR participants where separated into two groups: Current Cannabis Use (UHR-CU) and No Current Cannabis Use (UHR-NC). Healthy Control participants (HC) were free of cannabis use. Consistent with the literature, results indicate UHR individuals showed elevated cortisol levels when compared to HC participants. Further, we also observed that UHR-CU participants exhibited elevated levels when compared to both the non-using UHR and HC groups. Findings suggest that cannabis use may interact with underlying biological vulnerability associated with the hypothalamic-pituitary-adrenal (HPA) axis system.
Auditory stimulation of sleep slow oscillations modulates subsequent memory encoding through altered hippocampal function.
Sleep, 2018

Slow oscillations (SO) during sleep contribute to the consolidation of learned material. How the encoding of declarative memories during subsequent wakefulness might benefit from their enhancement during sleep is less clear. In this study, we investigated the impact of acoustically enhanced SO during a nap on subsequent encoding of declarative material.
Prognostic factors and health-related quality of life in ocular Myasthenia Gravis (OMG).
The International journal of neuroscience, 2014

We evaluate the factors predictive of prognosis in 91 Caucasian patients affected by ocular myasthenia gravis (OMG), followed at our Institution during an observational time, ranging from 12 to 240 months. The Myasthenia Gravis Foundation of America (MGFA) clinical classification was used to grade the disease severity. We considered as outcome measures the variation in two subscores, ocular (O-QMG) and nonocular (NO-QMG); the last one reflected bulbar, neck, extremity functions. None of the independent variables evaluated for association with the outcome, as age of onset, type of therapy, length of interval between first and last examinations, and presence of antibodies to acetylcholine receptors (AChR-Abs) significantly affected the evolution of O-QMG and of NO-QMG. Health-related quality of life (HRQol) was assessed in 63 patients. Variations of diplopia or ptosis did not affect significantly physical (PCS) or mental composite subscores (MCS) of the Short-Form Health Survey (SF-36). Human leukocyte antigen (HLA) genotyping was studied to explore whether HLA class I and II allelic distribution differed among MG patients and controls. None of the studied HLA alleles significantly differed between OMG patients and controls. Similarly, none of the alleles with frequencies higher than 15% either in OMG patients or in controls was significantly associated, after Bonferroni correction, with the presence or absence of anti-AChR-Abs in serum.
Structural Identification, Synthesis and Biological Activity of Two Volatile Cyclic Dipeptides in a Terrestrial Vertebrate.
Scientific reports, 2020

Single substances within complex vertebrate chemical signals could be physiologically or behaviourally active. However, the vast diversity in chemical structure, physical properties and molecular size of semiochemicals makes identifying pheromonally active compounds no easy task. Here, we identified two volatile cyclic dipeptides, cyclo(L-Leu-L-Pro) and cyclo(L-Pro-L-Pro), from the complex mixture of a chemical signal in terrestrial vertebrates (lizard genus Sceloporus), synthesised one of them and investigated their biological activity in male intra-specific communication. In a series of behavioural trials, lizards performed more chemosensory behaviour (tongue flicks, lip smacks and substrate lickings) when presented with the synthesised cyclo(L-Pro-L-Pro) chemical blend, compared to the controls, the cyclo(L-Leu-L-Pro) blend, or a combined blend with both cyclic dipeptides. The results suggest a potential semiochemical role of cyclo(L-Pro-L-Pro) and a modulating effect of cyclo(L-Leu-L-Pro) that may depend on the relative concentration of both compounds in the chemical signal. In addition, our results stress how minor compounds in complex mixtures can produce a meaningful behavioural response, how small differences in structural design are crucial for biological activity, and highlight the need for more studies to determine the complete functional landscape of biologically relevant compounds.
Application of morphometric analysis to patients with lung cancer metastasis to the spine: a clinical study.
Neurosurgical focus, 2016

OBJECTIVE Predicting the survival rate for patients with cancer is currently performed using the TNM Classification of Malignant Tumors (TNM). Identifying accurate prognostic markers of survival would allow better treatment stratification between more aggressive treatment strategies or palliation. This is especially relevant for patients with spinal metastases, who all have identical TNM staging and whose surgical decision-making is potentially complex. Analytical morphometrics quantifies patient frailty by measuring lean muscle mass and can predict risk for postoperative morbidity after lumbar spine surgery. This study evaluates whether morphometrics can be predictive of survival in patients with spinal metastases. METHODS Utilizing a retrospective registry of patients with spinal metastases who had undergone stereotactic body radiation therapy, the authors identified patients with primary lung cancer. Morphometric measurements were taken of the psoas muscle using CT of the lumbar spine. Additional morphometrics were taken of the L-4 vertebral body. Patients were stratified into tertiles based on psoas muscle area. The primary outcome measure was overall survival, which was measured from the date of the patient's CT scan to date of death. RESULTS A total of 168 patients were identified, with 54% male and 54% having multiple-level metastases. The median survival for all patients was 185.5 days (95% confidence interval [CI] 146-228 days). Survival was not associated with age, sex, or the number of levels of metastasis. Patients in the smallest tertile for the left psoas area had significantly shorter survival compared with a combination of the other two tertiles: 139 days versus 222 days, respectively, hazard ratio (HR) 1.47, 95% CI 1.06-2.04, p = 0.007. Total psoas tertiles were not predictive of mortality, but patients whose total psoas size was below the median size had significantly shorter survival compared with those greater than the median size: 146 days versus 253.5 days, respectively, HR 1.43, 95% CI 1.05-1.94, p = 0.025. To try to differentiate small body habitus from frailty, the ratio of psoas muscle area to vertebral body area was calculated. Total psoas size became predictive of mortality when normalized to vertebral body ratio, with patients in the lowest tertile having significantly shorter survival (p = 0.017). Left psoas to vertebral body ratio was also predictive of mortality in patients within the lowest tertile (p = 0.021). Right psoas size was not predictive of mortality in any calculations. CONCLUSIONS In patients with lung cancer metastases to the spine, morphometric analysis of psoas muscle and vertebral body size can be used to identify patients who are at risk for shorter survival. This information should be used to select patients who are appropriate candidates for surgery and for the tailoring of oncological treatment regimens.
The role of cyclin-dependent kinase 5 in neuropathic pain.
Pain, 2020

The chronification of pain can be attributed to changes in membrane receptors and channels underlying neuronal plasticity and signal transduction largely within nociceptive neurons that initiate and maintain pathological pain states. These proteins are subject to dynamic modification by posttranslational modifications, creating a code that controls protein function in time and space. Phosphorylation is an important posttranslational modification that affects ∼30% of proteins in vivo. Increased phosphorylation of various nociceptive ion channels and of their modulators underlies sensitization of different pain states. Cyclin-dependent kinases are proline-directed serine/threonine kinases that impact various biological and cellular systems. Cyclin-dependent kinase 5 (Cdk5), one member of this kinase family, and its activators p35 and p39 are expressed in spinal nerves, dorsal root ganglia, and the dorsal horn of the spinal cord. In neuropathic pain conditions, expression and/or activity of Cdk5 is increased, implicating Cdk5 in nociception. Experimental evidence suggests that Cdk5 is regulated through its own phosphorylation, through increasing p35's interaction with Cdk5, and through cleavage of p35 into p25. This narrative review discusses the molecular mechanisms of Cdk5-mediated regulation of target proteins involved in neuropathic pain. We focus on Cdk5 substrates that have been linked to nociceptive pathways, including channels (eg, transient receptor potential cation channel and voltage-gated calcium channel), proteins involved in neurotransmitter release (eg, synaptophysin and collapsin response mediator protein 2), and receptors (eg, glutamate, purinergic, and opioid). By altering the phosphoregulatory "set point" of proteins involved in pain signaling, Cdk5 thus appears to be an attractive target for treating neuropathic pain conditions.
Attention enhances stimulus representations in macaque visual cortex without affecting their signal-to-noise level.
Scientific reports, 2016

The magnitude of the attentional modulation of neuronal responses in visual cortex varies with stimulus contrast. Whether the strength of these attentional influences is similarly dependent on other stimulus properties is unknown. Here we report the effect of spatial attention on responses in the medial-temporal area (MT) of macaque visual cortex to moving random dots pattern of various motion coherences, i.e. signal-to-noise ratios. Our data show that allocating spatial attention causes a gain change in MT neurons. The magnitude of this attentional modulation is independent of the attended stimulus' motion coherence, creating a multiplicative scaling of the neuron's coherence-response function. This is consistent with the characteristics of gain models of attentional modulation and suggests that attention strengthens the neuronal representation of behaviorally relevant visual stimuli relative to unattended stimuli, but without affecting their signal-to-noise ratios.
Effects of Cyanidin-3-O-glucoside on Synthetic and Metabolic Activity of Ethanol Stimulated Human Pancreatic Stellate Cells.
Phytotherapy research : PTR, 2015

Activated pancreatic stellate cells (PSC) play a major role in the development of chronic pancreatitis. Flavonoids (C-3-O-G) theoretically may have potential to suppress activated PSC. The aim of our study was to determine the ability of C-3-O-G to invert synthetic and metabolic activity of alcohol stimulated human pancreatic stellate cells (hPSC). In the present study we demonstrate that treatment with C-3-O-G decreased proliferation rate of ethanol activated hPSC by 51%. Synthesis of extracellular matrix proteins in activated hPSC was markedly inhibited, as shown by reduced levels of collagen I and fibronectin expression. The decrease of secretion of fibronectin by 33% and in collagen I-25% in ethanol activated and C-3-O-G treated hPSC was observed. Moreover, treatment of ethanol activated hPSC with C-3-O-G resulted in the decrease of oxygen consumption rate by 44% and reduced levels of ATP synthesis (i.e. energy production) by 41%. Hence, the effects of C-3-O-G on ethanol activated hPSC may provide new insights for the use of anthocyanins as anti-fibrogenic agents in treatment and/or prevention of pancreatic fibrosis.
Endogenous signaling through alpha7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Neurogenesis in the dentate gyrus occurs throughout adult mammalian life and is essential for proper hippocampal function. Early in their development, adult-born neurons express homomeric alpha7-containing nicotinic acetylcholine receptors (alpha7-nAChRs) and receive direct cholinergic innervation. We show here that functional alpha7-nAChRs are necessary for normal survival, maturation, and integration of adult-born neurons in the dentate gyrus. Stereotaxic retroviral injection into the dentate gyrus of wild-type and alpha7-knock-out (alpha7KO) male and female mice was used to label and birthdate adult-born neurons for morphological and electrophysiological measures; BrdU (5-bromo-2-deoxyuridine) injections were used to quantify cell survival. In alpha7KO mice, we find that adult-born neurons develop with truncated, less complex dendritic arbors and display GABAergic postsynaptic currents with immature kinetics. The neurons also have a prolonged period of GABAergic depolarization characteristic of an immature state. In this condition, they receive fewer spontaneous synaptic currents and are more prone to die during the critical period when adult-born neurons are normally integrated into behaviorally relevant networks. Even those adult-born neurons that survive the critical period retain long-term dendritic abnormalities in alpha7KO mice. Interestingly, local infection with retroviral constructs to knockdown alpha7-mRNA mimics the alpha7KO phenotype, demonstrating that the relevant alpha7-nAChR signaling is cell autonomous. The results indicate a profound role for alpha7-nAChRs in adult neurogenesis and predict that alpha7-nAChR loss will cause progressive impairment in hippocampal circuitry and function over time as fewer neurons are added to the dentate gyrus and those that are added integrate less well.
Cortical Entropy, Mutual Information and Scale-Free Dynamics in Waking Mice.
Cerebral cortex (New York, N.Y. : 1991), 2016

Some neural circuits operate with simple dynamics characterized by one or a few well-defined spatiotemporal scales (e.g. central pattern generators). In contrast, cortical neuronal networks often exhibit richer activity patterns in which all spatiotemporal scales are represented. Such "scale-free" cortical dynamics manifest as cascades of activity with cascade sizes that are distributed according to a power-law. Theory and in vitro experiments suggest that information transmission among cortical circuits is optimized by scale-free dynamics. In vivo tests of this hypothesis have been limited by experimental techniques with insufficient spatial coverage and resolution, i.e., restricted access to a wide range of scales. We overcame these limitations by using genetically encoded voltage imaging to track neural activity in layer 2/3 pyramidal cells across the cortex in mice. As mice recovered from anesthesia, we observed three changes: (a) cortical information capacity increased, (b) information transmission among cortical regions increased and (c) neural activity became scale-free. Our results demonstrate that both information capacity and information transmission are maximized in the awake state in cortical regions with scale-free network dynamics.
The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) for Japanese ALS and FTD patients.
Amyotrophic lateral sclerosis & frontotemporal degeneration, 2021

Amyotrophic lateral sclerosis (ALS) patients might present with cognitive and behavioural abnormalities resembling frontotemporal dementia (FTD). The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was developed as an easy to administer cognitive screen for detecting these symptoms. The aim of the present study was to develop and validate a Japanese version of the ECAS.
Effectiveness of Equine-Assisted Activities and Therapies for Improving Adaptive Behavior and Motor Function in Autism Spectrum Disorder.
Journal of clinical medicine, 2021

Equine-assisted activities and therapies (EAAT) have been suggested to improve adaptive behavior, and possibly motor function, in autism spectrum disorder (ASD). This study investigated the effects of EAAT on adaptive behavior and motor function in 15 children with ASD (13 males) aged 7-15 years as well as the impact of EAAT on the magnitude of stress in the parent-child system and the evolution in the child interaction with both the trained therapist and the therapeutic animal through the 20 weekly sessions of EAAT. EAAT were associated with greater adaptive behavior and coordination (all
Challenge to Promote Change: The Neural Basis of the Contextual Interference Effect in Young and Older Adults.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018

Motor performance deteriorates with age. Hence, studying the effects of different training types on performance improvement is particularly important. Here, we investigated the neural correlates of the contextual interference (CI) effect in 32 young (YA; 16 female) and 28 older (OA; 12 female) human adults. Participants were randomly assigned to either a blocked or a random practice schedule, practiced three variations of a bimanual visuomotor task over 3 d, and were retested 6 d later. Functional magnetic resonance imaging data were acquired during the first and last training days and during retention. Although the overall performance level was lower in OA than YA, the typical CI effects were observed in both age groups, i.e., inferior performance during acquisition but superior performance during retention for random relative to blocked practice. At the neural level, blocked practice showed higher brain activity in motor-related brain regions compared with random practice across both age groups. However, although activity in these regions decreased with blocked practice in both age groups, it was either preserved (YA) or increased (OA) as a function of random practice. In contrast, random compared with blocked practice resulted in greater activations in visual processing regions across age groups. Interestingly, in OA, the more demanding random practice schedule triggered neuroplastic changes in areas of the default mode network, ultimately leading to better long-term retention. Our findings may have substantial implications for the optimization of practice schedules, and rehabilitation settings in particular.