rudyvdbrink/CitationDatabase huggingface dataset:
Nodal and paranodal antibody-associated neuropathies.
Practical neurology, 2021

Within the last decade, antibodies targeting the node and paranode of myelinated peripheral nerves have been increasingly identified in patients with acquired immune-mediated neuropathies, commonly termed 'nodo-paranodopathies'. Crucially, these patients often present with additional clinical features not usually seen with the most common immune-mediated neuropathies, Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, and respond poorly to conventionally used immunomodulatory therapies. Emerging evidence that these are pathologically distinct diseases has further prompted the use of more targeted treatment, such as the B cell depleting monoclonal antibody rituximab, which has been reported to significantly improve functional outcomes in this subset of patients. We provide an overview of the emerging clinical and serological phenotypes in patients with specific nodal/paranodal antibodies, the practicalities of antibody testing and current evidence supporting the use of non-standard therapies.
Molecular Mechanisms Related to Oxidative Stress in Retinitis Pigmentosa.
Antioxidants (Basel, Switzerland), 2021

Retinitis pigmentosa (RP) is an inherited retinopathy. Nevertheless, non-genetic biological factors play a central role in its pathogenesis and progression, including inflammation, autophagy and oxidative stress. The retina is particularly affected by oxidative stress due to its high metabolic rate and oxygen consumption as well as photosensitizer molecules inside the photoreceptors being constantly subjected to light/oxidative stress, which induces accumulation of ROS in RPE, caused by damaged photoreceptor's daily recycling. Oxidative DNA damage is a key regulator of microglial activation and photoreceptor degeneration in RP, as well as mutations in endogenous antioxidant pathways involved in DNA repair, oxidative stress protection and activation of antioxidant enzymes (
The role of amino-acid PET in the light of the new WHO classification 2016 for brain tumors.
The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of..., 2018

Since its introduction in 2016, the revision of the World Health Organization (WHO) classification of central nervous system tumors has already changed the diagnostic and therapeutic approach in glial tumors. Blurring the lines between entities formerly labelled as "high-grade" or "low-grade", molecular markers define distinct biological subtypes with different clinical course. This new classification raises the demand for non-invasive imaging methods focusing on depicting metabolic processes. We performed a review of current literature on the use of amino-acid PET (AA-PET) for obtaining diagnostic or prognostic information on glioma in the setting of the current WHO 2016 classification. So far, only a few studies have focused on combining molecular genetic information and metabolic imaging using AA-PET. The current review summarizes the information available on "molecular grading" as well as prognostic information obtained from AA-PET and delivers an insight into a possible interrelation between metabolic imaging and glioma genetics. Within the framework of molecular characterization of gliomas, metabolic imaging using AA-PET is a promising tool for non-invasive characterization of molecular features and to provide additional prognostic information. Further studies incorporating molecular and metabolic features are necessary to improve the explanatory power of AA-PET in glial tumors.
Morpho-physiologic characteristics of dorsal subicular network in mice after pilocarpine-induced status epilepticus.
Brain pathology (Zurich, Switzerland), 2010

The goal of this study was to examine the morpho-physiologic changes in the dorsal subiculum network in the mouse model of temporal lobe epilepsy using extracellular recording, juxtacellular and immunofluorescence double labeling, and anterograde tracing methods. A significant loss of total dorsal subicular neurons, particularly calbindin, parvalbumin (PV) and immunopositive interneurons, was found at 2 months after pilocarpine-induced status epilepticus (SE). However, the sprouting of axons from lateral entorhinal cortex (LEnt) was observed to contact with surviving subicular neurons. These neurons had two predominant discharge patterns: bursting and fast irregular discharges. The bursting neurons were mainly pyramidal cells, and their dendritic spine density and bursting discharge rates were increased significantly in SE mice compared with the control group. Fast irregular discharge neurons were PV-immunopositive interneurons and had less dendritic spines in SE mice when compared with the control mice. When LEnt was stimulated, bursting and fast irregular discharge neurons had much shorter latency and stronger excitatory response in SE mice compared with the control group. Our results illustrate that morpho-physiologic changes in the dorsal subiculum could be part of a multilevel pathologic network that occurs simultaneously in many brain areas to contribute to the generation of epileptiform activity.
Contributions of different modes of TRPV1 activation to TRPV1 antagonist-induced hyperthermia.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010

Transient receptor potential vanilloid-1 (TRPV1) antagonists are widely viewed as next-generation pain therapeutics. However, these compounds cause hyperthermia, a serious side effect. TRPV1 antagonists differentially block three modes of TRPV1 activation: by heat, protons, and chemical ligands (e.g., capsaicin). We asked what combination of potencies in these three modes of TRPV1 activation corresponds to the lowest potency of a TRPV1 antagonist to cause hyperthermia. We studied hyperthermic responses of rats, mice, and guinea pigs to eight TRPV1 antagonists with different pharmacological profiles and used mathematical modeling to find a relative contribution of the blockade of each activation mode to the development of hyperthermia. We found that the hyperthermic effect has the highest sensitivity to the extent of TRPV1 blockade in the proton mode (0.43 to 0.65) with no to moderate sensitivity in the capsaicin mode (-0.01 to 0.34) and no sensitivity in the heat mode (0.00 to 0.01). We conclude that hyperthermia-free TRPV1 antagonists do not block TRPV1 activation by protons, even if they are potent blockers of the heat mode, and that decreasing the potency to block the capsaicin mode may further decrease the potency to cause hyperthermia.
Reprogramming of microRNA expression via E2F1 downregulation promotes Salmonella infection both in infected and bystander cells.
Nature communications, 2021

Cells infected with pathogens can contribute to clearing infections by releasing signals that instruct neighbouring cells to mount a pro-inflammatory cytokine response, or by other mechanisms that reduce bystander cells' susceptibility to infection. Here, we show the opposite effect: epithelial cells infected with Salmonella Typhimurium secrete host factors that facilitate the infection of bystander cells. We find that the endoplasmic reticulum stress response is activated in both infected and bystander cells, and this leads to activation of JNK pathway, downregulation of transcription factor E2F1, and consequent reprogramming of microRNA expression in a time-dependent manner. These changes are not elicited by infection with other bacterial pathogens, such as Shigella flexneri or Listeria monocytogenes. Remarkably, the protein HMGB1 present in the secretome of Salmonella-infected cells is responsible for the activation of the IRE1 branch of the endoplasmic reticulum stress response in non-infected, neighbouring cells. Furthermore, E2F1 downregulation and the associated microRNA alterations promote Salmonella replication within infected cells and prime bystander cells for more efficient infection.
Most patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency develop pathological or subnormal retinal function.
Acta paediatrica (Oslo, Norway : 1992), 2016

There have been few studies on long-term electroretinographic findings in patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). This study correlated long-term electroretinographic findings with age, metabolic control and clinical symptoms.
Facing up to the wandering mind: Patterns of off-task laboratory thought are associated with stronger neural recruitment of right fusiform cortex while processing facial stimuli.
NeuroImage, 2020

Human cognition is not always tethered to events in the external world. Laboratory and real world experience sampling studies reveal that attention is often devoted to self-generated mental content rather than to events taking place in the immediate environment. Recent studies have begun to explicitly examine the consistency between states of off-task thought in the laboratory and in daily life, highlighting differences in the psychological correlates of these states across the two contexts. Our study used neuroimaging to further understand the generalizability of off-task thought across laboratory and daily life contexts. We examined (1) whether context (daily life versus laboratory) impacts on individuals' off-task thought patterns and whether individual variations in these patterns are correlated across contexts; (2) whether neural correlates for the patterns of off-task thoughts in the laboratory show similarities with those thoughts in daily life, in particular, whether differences in cortical grey matter associated with detail and off-task thoughts in the para-hippocampus, identified in a prior study on laboratory thoughts, were apparent in real life thought patterns. We also measured neural responses to common real-world stimuli (faces and scenes) and examined how neural responses to these stimuli were related to experiences in the laboratory and in daily life - finding evidence of both similarities and differences. There were consistent patterns of off-task thoughts reported across the two contexts, and both patterns had a commensurate relationship with medial temporal lobe architecture. However, compared to real world off-task thoughts, those in the laboratory focused more on social content and showed a stronger correlation with neural activity when viewing faces compared to scenes. Overall our results show that off-task thought patterns have broad similarities in the laboratory and in daily life, and the apparent differences may be, in part, driven by the richer environmental context in the real world. More generally, our findings are broadly consistent with emerging evidence that shows off-task thoughts emerge through the prioritisation of information that has greater personal relevance than events in the here and now.
Are gonadal steroids linked with orgasm perceptions and sexual assertiveness in women and men?
Hormones and behavior, 2009

Past findings suggest links between orgasms and testosterone (T), as well as sexuality and estradiol (E), and we examined hormone-orgasm links in this study via two hypotheses (below). Participants were 86 women and 91 men who provided a saliva sample and completed a demographics questionnaire, the Orgasm Checklist (Mah and Binik, 2002), the Hurlbert (1991) Index of Sexual Assertiveness, and the Sexual Desire Inventory (Spector and Fremeth, 1996). Results supported the first hypothesis of correlations between T and positive orgasm experience in women, specifically with the relaxation, soothing, and peaceful items in both partnered and solitary orgasm contexts. Results also indicated correlations between E and flooding and spreading items in a solitary orgasm context. There were no associations between hormones and men's perceptions of their orgasm experiences. There was no support for the second hypothesis of associations between higher T and more sexual assertiveness. Post hoc analyses showed associations between E and women's sexual desire, and T and men's sexual desire. We discuss implications of these findings including that solitary vs. partnered orgasm experiences may differ, and suggest that T might be associated with perceptions of psychological experiences of orgasms, and E might be associated with perceptions of physical experiences of orgasms.
Cell-type-specific inhibition of the dendritic plateau potential in striatal spiny projection neurons.
Proceedings of the National Academy of Sciences of the United States of America, 2017

Striatal spiny projection neurons (SPNs) receive convergent excitatory synaptic inputs from the cortex and thalamus. Activation of spatially clustered and temporally synchronized excitatory inputs at the distal dendrites could trigger plateau potentials in SPNs. Such supralinear synaptic integration is crucial for dendritic computation. However, how plateau potentials interact with subsequent excitatory and inhibitory synaptic inputs remains unknown. By combining computational simulation, two-photon imaging, optogenetics, and dual-color uncaging of glutamate and GABA, we demonstrate that plateau potentials can broaden the spatiotemporal window for integrating excitatory inputs and promote spiking. The temporal window of spiking can be delicately controlled by GABAergic inhibition in a cell-type-specific manner. This subtle inhibitory control of plateau potential depends on the location and kinetics of the GABAergic inputs and is achieved by the balance between relief and reestablishment of NMDA receptor Mg
Ephrin-A2 affects wound healing and scarring in a murine model of excisional injury.
Burns : journal of the International Society for Burn Injuries, 2019

Ephrin ligand/Eph receptor signaling is important in both tissue development and homeostasis. There is increasing evidence that Ephrin/Eph signaling is important in the skin, involved in hair follicle cycling, epidermal differentiation, cutaneous innervation and skin cancer. However, there is currently limited information on the role of Ephrin/Eph signaling in cutaneous wound healing. Here we report the effects of the Ephrin-A2 and A5 ligands on wound healing. Using Ephrin-A2
Plasma corticosterone levels in mouse models of pain.
European journal of pain (London, England), 2012

Pain markedly activates the hypothalamic-pituitary-adrenal (HPA) axis and increases plasma corticosterone release interfering significantly with nociceptive behaviour as well as the mechanism of action of analgesic drugs.
Saliency-guided neural prosthesis for visual attention: design and simulation.
Neuroscience research, 2014

Recently the authors showed that a computational model of visual saliency could account for changes in gaze behavior of monkeys with damage in the primary visual cortex. Here we propose a neural prosthesis to restore eye gaze behavior by electrically stimulating the superior colliculus to drive visual attention. The saliency computational model is used to calculate the stimulation parameters from a real-time camera stream. Our simulations demonstrate that electrodes implanted in the superior colliculus at 1.0mm spacing are, in principle, able to recover specifically those visual attention behaviors which are lost when the primary visual cortex is damaged.
Exploring myelin dysfunction in multiple system atrophy.
Experimental neurobiology, 2014

Multiple system atrophy (MSA) is a rare, yet fatal neurodegenerative disease that presents clinically with autonomic failure in combination with parkinsonism or cerebellar ataxia. MSA impacts on the autonomic nervous system affecting blood pressure, heart rate and bladder function, and the motor system affecting balance and muscle movement. The cause of MSA is unknown, no definitive risk factors have been identified, and there is no cure or effective treatment. The definitive pathology of MSA is the presence of α-synuclein aggregates in the brain and therefore MSA is classified as an α-synucleinopathy, together with Parkinson's disease and dementia with Lewy bodies. Although the molecular mechanisms of misfolding, fibrillation and aggregation of α-synuclein partly overlap with other α-synucleinopathies, the pathological pathway of MSA is unique in that the principal site for α-synuclein deposition is in the oligodendrocytes rather than the neurons. The sequence of pathological events of MSA is now recognized as abnormal protein redistributions in oligodendrocytes first, followed by myelin dysfunction and then neurodegeneration. Oligodendrocytes are responsible for the production and maintenance of myelin, the specialized lipid membrane that encases the axons of all neurons in the brain. Myelin is composed of lipids and two prominent proteins, myelin basic protein and proteolipid protein. In vitro studies suggest that aberration in protein distribution and lipid transport may lead to myelin dysfunction in MSA. The purpose of this perspective is to bring together available evidence to explore the potential role of α-synuclein, myelin protein dysfunction, lipid dyshomeostasis and ABCA8 in MSA pathogenesis.
Male adolescent rats display blunted cytokine responses in the CNS after acute ethanol or lipopolysaccharide exposure.
Physiology & behavior, 2015

Alcohol induces widespread changes in cytokine expression, with recent data from our laboratory having demonstrated that, during acute ethanol intoxication, adult rats exhibit consistent increases in interleukin (IL)-6 mRNA expression in several brain regions, while showing reductions in IL-1 and TNFα expression. Given evidence indicating that adolescence may be an ontogenetic period in which some neuroimmune processes and cells may not yet have fully matured, the purpose of the current experiments was to examine potential age differences in the central cytokine response of adolescent (P31-33days of age) and adult (69-71days of age) rats to either an acute immune (lipopolysaccharide; LPS) or non-immune challenge (ethanol). In Experiment 1, male Sprague-Dawley rats were given an intraperitoneal (i.p.) injection of either sterile saline, LPS (250μg/kg), or ethanol (4-g/kg), and then trunk blood and brain tissue were collected 3h later for measurement of blood ethanol concentrations (BECs), plasma endotoxin, and central mRNA expression of several immune-related gene targets. In Experiment 2, the response to intragastrically (i.g.) administered ethanol was examined and compared to animals given tap water (i.g.). Results showed that LPS stimulated robust increases in expression of IL-1, IL-6, TNFα, and IκBα in the hippocampus, PVN, and amygdala, and that these increases were generally less pronounced in adolescents relative to adults. Following an i.p. ethanol challenge, IL-6 and IκBα expression was significantly increased in both ages in the PVN and amygdala, and adults exhibited even greater increases in IκBα than adolescents. I.g. administration of ethanol also increased IL-6 and IκBα expression in all three brain regions, with hippocampal IL-6 elevated even more so in adults compared to adolescents. Furthermore, assessment of plasma endotoxin concentrations revealed (i) whereas robust increases in plasma endotoxin were observed in adults injected with LPS, no corresponding elevations were seen in adolescents after LPS; and (ii) neither adolescents nor adults demonstrated increases in plasma endotoxin concentrations following i.p. or i.g. ethanol administration. Analysis of BECs indicated that, for both routes of exposure, adolescents exhibited lower BECs than adults. Taken together, these data suggest that categorically different mechanisms are involved in the central cytokine response to antigen exposure versus ethanol administration. Furthermore, these findings confirm once again that acute ethanol intoxication is a potent activator of brain cytokines, and calls for future studies to identify the mechanisms underlying age-related differences in the cytokine response observed during ethanol intoxication.
Predicting nonroutine discharge after elective spine surgery: external validation of machine learning algorithms.
Journal of neurosurgery. Spine, 2019

Nonroutine discharge after elective spine surgery increases healthcare costs, negatively impacts patient satisfaction, and exposes patients to additional hospital-acquired complications. Therefore, prediction of nonroutine discharge in this population may improve clinical management. The authors previously developed a machine learning algorithm from national data that predicts risk of nonhome discharge for patients undergoing surgery for lumbar disc disorders. In this paper the authors externally validate their algorithm in an independent institutional population of neurosurgical spine patients.
Light-Induced Opening of the TRP Channel in Isolated Membrane Patches Excised from Photosensitive Microvilli from Drosophila Photoreceptors.
Neuroscience, 2019

Drosophila phototransduction occurs in light-sensitive microvilli arranged in a longitudinal structure of the photoreceptor, termed the rhabdomere. Rhodopsin (Rh), isomerized by light, couples to G-protein, which activates phospholipase C (PLC), which in turn cleaves phosphatidylinositol 4,5-bisphosphate (PIP
Temporo-Frontal Coherences and High-Frequency iEEG Responses during Spatial Navigation in Patients with Drug-Resistant Epilepsy.
Brain sciences, 2021

The prefrontal cortex and hippocampus function in tight coordination during multiple cognitive processes. During spatial navigation, prefrontal neurons are linked to hippocampal theta oscillations, presumably in order to enhance communication. Hippocampal ripples have been suggested to reflect spatial memory processes. Whether prefrontal-hippocampal-interaction also takes place within the ripple band is unknown. This intracranial EEG study aimed to investigate whether ripple band coherences can also be used to show this communication. Twelve patients with epilepsy and intracranial EEG evaluation completed a virtual spatial navigation task. We calculated ordinary coherence between prefrontal and temporal electrodes during retrieval, re-encoding, and pre-task rest. Coherences were compared between the conditions via permutation testing. Additionally, ripples events were automatically detected and changes in occurrence rates were investigated excluding ripples on epileptic spikes. Ripple-band coherences yielded no general effect of the task on coherences across all patients. Furthermore, we did not find significant effects of task conditions on ripple rates. Subsequent analyses pointed to rather short periods of synchrony as opposed to general task-related changes in ripple-band coherence. Specifically designed tasks and adopted measures might be necessary in order to map these interactions in future studies.