rudyvdbrink/CitationDatabase huggingface dataset:
Less invasive palliative surgery for spinal metastases.
Journal of surgical oncology, 2013

There may be patients with spinal metastasis for whom neither vertebroplasty/kyphoplasty nor open surgery is appropriate. Percutaneous pedicle screw fixation (PPSF) may fill the gap between techniques.
In vitro effects of cocaine on tunneling nanotube formation and extracellular vesicle release in glioblastoma cell cultures.
Journal of molecular neuroscience : MN, 2015

The effects of cocaine (150 nM, 300 nM, and 150 μM) on human glioblastoma cell cultures were studied on tunneling nanotube formation (1-h cocaine treatment) and extracellular vesicle release (1-, 3-, and 8-h cocaine treatment). Cocaine significantly increased the number of tunneling nanotubes only at the lowest concentration used. The release of extracellular vesicles (mainly exosomes) into the medium was stimulated by cocaine at each concentration used with a maximum effect at the highest concentration tested (150 μM). Moreover, cocaine (150 nM) significantly increased the number of vesicles with 61-80 nm diameter while at concentrations of 300 nM and 150 μM, and the smaller vesicles (30-40 nm diameter) were significantly increased with a reduction of the larger vesicles (41-60 nm diameter). A time dependence in the release of extracellular vesicles was observed. In view of the proposed role of these novel intercellular communication modes in the glial-neuronal plasticity, it seems possible that they can participate in the processes leading to cocaine addiction. The molecular target/s involved in these cocaine effects could be specific molecular components of plasma membrane lipid rafts and/or cocaine-induced modifications in cytoplasmic lipid composition.
Essential role of microglial transforming growth factor-β1 in antidepressant actions of (R)-ketamine and the novel antidepressant TGF-β1.
Translational psychiatry, 2020

In rodent models of depression, (R)-ketamine has greater potency and longer-lasting antidepressant effects than (S)-ketamine; however, the precise molecular mechanisms underlying the antidepressant actions of (R)-ketamine remain unknown. Using RNA-sequencing analysis, we identified novel molecular targets that contribute to the different antidepressant effects of the two enantiomers. Either (R)-ketamine (10 mg/kg) or (S)-ketamine (10 mg/kg) was administered to susceptible mice after chronic social defeat stress (CSDS). RNA-sequencing analysis of prefrontal cortex (PFC) and subsequent GSEA (gene set enrichment analysis) revealed that transforming growth factor (TGF)-β signaling might contribute to the different antidepressant effects of the two enantiomers. (R)-ketamine, but not (S)-ketamine, ameliorated the reduced expressions of Tgfb1 and its receptors (Tgfbr1 and Tgfbr2) in the PFC and hippocampus of CSDS susceptible mice. Either pharmacological inhibitors (i.e., RepSox and SB431542) or neutralizing antibody of TGF-β1 blocked the antidepressant effects of (R)-ketamine in CSDS susceptible mice. Moreover, depletion of microglia by the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX3397 blocked the antidepressant effects of (R)-ketamine in CSDS susceptible mice. Similar to (R)-ketamine, the recombinant TGF-β1 elicited rapid and long-lasting antidepressant effects in animal models of depression. Our data implicate a novel microglial TGF-β1-dependent mechanism underlying the antidepressant effects of (R)-ketamine in rodents with depression-like phenotype. Moreover, TGF-β1 and its receptor agonists would likely constitute a novel rapid-acting and sustained antidepressant in humans.
Modafinil reinstates a cocaine conditioned place preference following extinction in rats.
Behavioural brain research, 2009

The current study examined whether modafinil would reinstate an extinguished cocaine conditioned place preference (CPP). Following extinction of a cocaine CPP, rats were administered modafinil (128 mg/kg), cocaine (5 mg/kg) or vehicle and given a 60-min reinstatement test. While the effect of cocaine was transient, modafinil robustly reinstated a cocaine CPP following extinction, suggesting that modafinil may induce relapse or increase the vulnerability of addicts to the reinforcing effects of environmental triggers.
Moyamoya vasculopathy - Patient demographics and characteristics in the Finnish population.
International journal of stroke : official journal of the International Stroke Society, 2017

Background and purpose Moyamoya vasculopathy, a rare steno-occlusive progressive cerebrovascular disorder, has not been thoroughly studied in Caucasian populations. We established a registry of Finnish patients treated at the Helsinki University Hospital, to collect and report demographic and clinical data. Methods We collected data both retrospectively and prospectively from all the patients with a moyamoya vasculopathy referred to our hospital between January 1987 and December 2014. All patients underwent a neurological outpatient clinic visit. Results We diagnosed 61 patients (50 females, 10 children) with moyamoya vasculopathy. The mean age at the disease-onset was 31.5 ± 17.9 years. The two most common presenting symptoms were ischemic stroke (n = 31) and hemorrhage (n = 8). Forty-four percent underwent revascularization surgery, and 70% were prescribed antithrombotic treatment. Conclusions The results support in part the Western phenotype of the disease considering the later presentation and larger female predominance compared to the Asian moyamoya vasculopathy reports. However, the proportion of ischemic strokes and hemorrhagic strokes is closer to Japanese population than German population. The absence of familial cases points to a different genetic profile in the Finnish patients.
Design and structural characterisation of olfactomedin-1 variants as tools for functional studies.
BMC molecular and cell biology, 2019

Olfactomedin-1 (Olfm1; also known as Noelin or Pancortin) is a highly-expressed secreted brain and retina protein and its four isoforms have different roles in nervous system development and function. Structural studies showed that the long Olfm1 isoform BMZ forms a disulfide-linked tetramer with a V-shaped architecture. The tips of the Olfm1 "V" each consist of two C-terminal β-propeller domains that enclose a calcium binding site. Functional characterisation of Olfm1 may be aided by new biochemical tools derived from these core structural elements.
Factors controlling the input-output relationship of spherical bushy cells in the gerbil cochlear nucleus.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Despite the presence of large endbulb inputs, the spherical bushy cells (SBCs) of the rostral anteroventral cochlear nucleus do not function as simple auditory relays. We used the good signal-to-noise ratio of juxtacellular recordings to dissect the intrinsic and network mechanisms controlling the input-output relationship of SBCs in anesthetized gerbils. The SBCs generally operated close to action potential (AP) threshold and showed no evidence for synaptic depression, suggesting that the endbulbs of Held have low release probability in vivo. Analysis of the complex waveforms suggested that in the absence of auditory stimulation, postsynaptic spike depression and stochastic fluctuations in EPSP size were the main factors determining jitter and reliability of the endbulb synapse. During auditory stimulation, progressively larger EPSPs were needed to trigger APs at increasing sound intensities. Simulations suggested hyperpolarizing inhibition could explain the observed decrease in EPSP efficacy. Synaptic inhibition showed a delayed onset and generally had a higher threshold than excitatory inputs, but otherwise inhibition and excitation showed mostly overlapping frequency-response areas. The recruitment of synaptic inhibition caused postsynaptic spikes to be preferentially triggered by well-timed, large EPSPs, resulting in improved phase locking despite more variable EPSP-AP latencies. Our results suggest that the lack of synaptic depression, caused by low release probability, and the apparent absence of sound-evoked synaptic inhibition at low sound intensity maximize sensitivity of SBCs. At higher sound intensities, the recruitment of synaptic inhibition constrains their firing rate and optimizes their temporal precision.
Dynamic and persistent effects of ethanol exposure on development: an in vivo analysis during and after embryonic ethanol exposure in Caenorhabditis elegans.
Alcoholism, clinical and experimental research, 2013

Defects caused by ethanol (EtOH) exposure during development can be different depending on the time of observation. To investigate this temporal component of developmental delay, we use the fast-developing nematode model Caenorhabditis elegans. We first defined the longitudinal effects of EtOH on development using age-appropriate markers and then closely followed embryonic development before, during, and after EtOH exposure.
P/Q-type calcium channel modulators.
British journal of pharmacology, 2012

P/Q-type calcium channels are high-voltage-gated calcium channels contributing to vesicle release at synaptic terminals. A number of neurological diseases have been attributed to malfunctioning of P/Q channels, including ataxia, migraine and Alzheimer's disease. To date, only two specific P/Q-type blockers are known: both are peptides deriving from the spider venom of Agelenopsis aperta, ω-agatoxins. Other peptidic calcium channel blockers with activity at P/Q channels are available, albeit with less selectivity. A number of low molecular weight compounds modulate P/Q-type currents with different characteristics, and some exhibit a peculiar bidirectional pattern of modulation. Interestingly, there are a number of therapeutics in clinical use, which also show P/Q channel activity. Because selectivity as well as the exact mode of action is different between all P/Q-type channel modulators, the interpretation of clinical and experimental data is complicated and needs a comprehensive understanding of their target profile. The situation is further complicated by the fact that information on potency varies vastly in the literature, which may be the result of different experimental systems, conditions or the splice variants of the P/Q channel. This review attempts to provide a comprehensive overview of the compounds available that affect the P/Q-type channel and should help with the interpretation of results of in vitro experiments and animal models. It also aims to explain some clinical observations by implementing current knowledge about P/Q channel modulation of therapeutically used non-selective drugs. Chances and challenges of the development of P/Q channel-selective molecules are discussed.
Prenatal poly I:C age-dependently alters cannabinoid type 1 receptors in offspring: a longitudinal small animal PET study using [(18)F]MK-9470.
Experimental neurology, 2014

Evidence suggests that there is a link between the endocannabinoid system (ECS) and neuropsychiatric illnesses, including schizophrenia. Whilst the ECS has been shown to be involved in immune system regulation in various ways, it is known that infections during pregnancy can modulate the immune system of the mother and increase the risk for schizophrenia in offspring. In animal studies, maternal immune activation following administration of viral or bacterial mimics has been shown to reproduce many key structural, behavioural, and pharmacological abnormalities in offspring that resemble schizophrenia. In the present study, we used Positron Emission Tomography (PET) and [(18)F]MK-9470, a selective high-affinity inverse agonist radioligand for cannabinoid type 1 receptors (CB1R), to longitudinally assess CB1R expression in the progeny of female rats exposed to the viral mimic polyriboinosinic-polyribocytidilic acid (poly I:C) (4mg/kg i.v.) or vehicle at gestational day 15 (GD 15). PET scans were performed in offspring at postnatal days (PND) 32-42 (adolescence) and in the same animals again at PNDs 75-79 (adulthood). Sixteen regions of interest were assessed, encompassing the whole rat brain. At adolescence, offspring exposed prenatally to poly I:C had significantly lower CB1R relative Standard Uptake Values (rSUV) compared to controls in the globus pallidus (p=0.046). In adulthood, however, poly I:C exposed offspring had higher levels of CB1R rSUV in sensory cortex (p=0.034) and hypothalamus (p=0.032) compared to controls. Our results suggest that prenatal poly I:C leads to long term alterations in the integrity of the ECS that are age and region-specific. The increased CB1R expression in adulthood following poly I:C mirrors the increased CB1R observed in patients with schizophrenia in post-mortem and in vivo PET studies.
Subcortical epilepsy?
Neurology, 2013

In the past, the cortex has for the most part been considered to be the site of seizure origin in the different forms of epilepsy. Findings from histopathologic, electrophysiologic, and brain imaging studies now provide ample evidence demonstrating that like normal cerebral function, epileptic seizures involve widespread network interactions between cortical and subcortical structures. These studies show that different forms of generalized and focal epileptiform discharges and seizures engage various subcortical structures in varying ways. This interaction has been the subject of many reviews and is not the focus of the current work. The aim of this review is to examine the evidence suggesting the possibility for some of the subcortical structures to initiate seizures independently and the clinical implications of this.
The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative.
Nature reviews. Neurology, 2016

Over the past few years, MRI has become an indispensable tool for diagnosing multiple sclerosis (MS). However, the current MRI criteria for MS diagnosis have imperfect sensitivity and specificity. The central vein sign (CVS) has recently been proposed as a novel MRI biomarker to improve the accuracy and speed of MS diagnosis. Evidence indicates that the presence of the CVS in individual lesions can accurately differentiate MS from other diseases that mimic this condition. However, the predictive value of the CVS for the development of clinical MS in patients with suspected demyelinating disease is still unknown. Moreover, the lack of standardization for the definition and imaging of the CVS currently limits its clinical implementation and validation. On the basis of a thorough review of the existing literature on the CVS and the consensus opinion of the members of the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative, this article provides statements and recommendations aimed at helping radiologists and neurologists to better understand, refine, standardize and evaluate the CVS in the diagnosis of MS.
Reverse GWAS: Using genetics to identify and model phenotypic subtypes.
PLoS genetics, 2019

Recent and classical work has revealed biologically and medically significant subtypes in complex diseases and traits. However, relevant subtypes are often unknown, unmeasured, or actively debated, making automated statistical approaches to subtype definition valuable. We propose reverse GWAS (RGWAS) to identify and validate subtypes using genetics and multiple traits: while GWAS seeks the genetic basis of a given trait, RGWAS seeks to define trait subtypes with distinct genetic bases. Unlike existing approaches relying on off-the-shelf clustering methods, RGWAS uses a novel decomposition, MFMR, to model covariates, binary traits, and population structure. We use extensive simulations to show that modelling these features can be crucial for power and calibration. We validate RGWAS in practice by recovering a recently discovered stress subtype in major depression. We then show the utility of RGWAS by identifying three novel subtypes of metabolic traits. We biologically validate these metabolic subtypes with SNP-level tests and a novel polygenic test: the former recover known metabolic GxE SNPs; the latter suggests subtypes may explain substantial missing heritability. Crucially, statins, which are widely prescribed and theorized to increase diabetes risk, have opposing effects on blood glucose across metabolic subtypes, suggesting the subtypes have potential translational value.
Spatial and temporal requirements for huntingtin (Htt) in neuronal migration and survival during brain development.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Huntington's disease (HD), caused by an expanded triplet repeat in the huntingtin (Htt) gene, results in extensive neuropathology, but study of the Htt gene in CNS development through gene knockout is problematic as the knockout leads to embryonic lethality in mice. Here, we report that the knockdown of Htt expression in neuroepithelial cells of neocortex results in disturbed cell migration, reduced proliferation, and increased cell death that is relatively specific to early neural development. In the cerebellum, however, Htt knockdown results in cell death but not perturbed migration. The cell death phenotype in cortex can be partially reversed with co-knockdown of Casp9, indicating that mitochondria-mediated cell apoptotic processes are involved in the neuronal death. The timing of knockdown during early development is also an important variable. These results indicate a spatial and temporal requirement for Htt expression in neural development. Although it is uncertain whether the loss of wild-type huntingtin function contributes to pathogenesis in Huntington's disease, these results clearly contraindicate the use of nonspecific knockdown of Htt as a therapeutic measure in HD, particularly in utero.
Metabolic brain networks in neurodegenerative disorders: a functional imaging approach.
Trends in neurosciences, 2009

Network analysis of functional brain imaging data is an innovative approach to study circuit abnormalities in neurodegenerative diseases. In Parkinson's disease, spatial covariance analysis of resting-state metabolic images has identified specific regional patterns associated with motor and cognitive symptoms. With functional imaging, these metabolic networks have recently been used to measure system-related progression and to evaluate novel treatment strategies. Network analysis is also being used to characterize specific functional biomarkers for Huntington's disease and Alzheimer's disease. These networks have been particularly helpful in uncovering compensatory mechanisms in genetically at-risk individuals. Ongoing developments in network applications are likely to enhance the role of functional imaging in the investigation of neurodegenerative disorders.
Evaluation of corticospinal excitability in cervical myelopathy, before and after surgery, with transcranial magnetic stimulation: a pilot study.
European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 2013

A pilot study to examine the impact of cervical myelopathy on corticospinal excitability, using transcranial magnetic stimulation, and to investigate whether motor evoked potential (MEP) and silent period (SP) recruitment curve (RC) parameters can detect changes in corticospinal function pre- and post-surgery.
TNF and its receptors in the CNS: The essential, the desirable and the deleterious effects.
Neuroscience, 2015

Tumor necrosis factor (TNF) is the prototypic pro-inflammatory cytokine. It is central to host defense and inflammatory responses but under certain circumstances also triggers cell death and tissue degeneration. Its pleiotropic effects often lead to opposing outcomes during the development of immune-mediated diseases, particularly those affecting the central nervous system (CNS). The reported contradictions may result from lack of precision in discussing TNF. TNF signaling comprises at minimum a two-ligand (soluble and transmembrane TNF) and two-receptor (TNFR1 and TNFR2) system, with ligands and receptors both differentially expressed and regulated on different cell types. The "functional multiplicity" this engenders is the focus of much research, but there is still no general consensus on functional outcomes of TNF signaling in general, let alone in the CNS. In this review, evidence showing the effects of TNF in the CNS under physiological and pathophysiological conditions is placed in the context of major advances in understanding of the cellular and molecular mechanisms that govern TNF function in general. Thus the roles of TNF signaling in the CNS shift from the conventional dichotomy of beneficial and deleterious, that mainly explain effects under pathological conditions, to incorporate a growing number of "essential" and "desirable" roles for TNF and its main cellular source in the CNS, microglia, under physiological conditions including regulation of neuronal activity and maintenance of myelin. An improved holistic view of TNF function in the CNS might better reconcile the expansive experimental data with stark clinical evidence that reduced functioning of TNF and its dominant pro-inflammatory receptor, TNFR1, are risk factors for the development of multiple sclerosis. It will also facilitate the safe translation of basic research findings from animal models to humans and propel the development of more selective anti-TNF therapies aimed at selectively inhibiting deleterious effects of this cytokine while maintaining its essential and desirable ones, in the periphery and the CNS.
Response normalization in the superficial layers of the superior colliculus as a possible mechanism for saccadic averaging.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

How does the brain decide where to look? Neuronal networks within the superior colliculus (SC) encode locations of intended eye movements. When faced with multiple targets, the relative activities of neuronal populations compete for the selection of a saccade. However, the computational principles underlying saccadic choices remain poorly understood. We used voltage imaging of slices of rat SC to record circuit dynamics of population responses to single- and dual-site electrical stimulation to begin to reveal some of the principles of how populations of neurons interact. Stimulation of two distant sites simultaneously within the SC produced two distinct peaks of activity, whereas stimulation of two nearby sites simultaneously exhibited a single, merged peak centered between the two sites. The distances required to produce merged peaks of activity corresponded to target separations that evoked averaging saccades in humans performing a corresponding dual target task. The merged activity was well accounted for by a linear weighed summation and a divisive normalization of the responses evoked by the single-site stimulations. Interestingly, the merging of activity occurred within the superficial SC, suggesting a novel pathway for saccadic eye movement choice.