rudyvdbrink/CitationDatabase huggingface dataset:
Sympathetic regulation and anterior cingulate cortex volume are altered in a rat model of chronic back pain.
Neuroscience, 2017

Chronic pain is associated with autonomic disturbance. However, specific effects of chronic back pain on sympathetic regulation remain unknown. Chronic pain is also associated with structural changes in the anterior cingulate cortex (ACC), which may be linked to sympathetic dysregulation. The aim of this study was to determine whether sympathetic regulation and ACC surface and volume are affected in a rat model of chronic back pain, in which complete Freund Adjuvant (CFA) is injected in back muscles. Sympathetic regulation was assessed with renal blood flow (RBF) changes induced by electrical stimulation of a hind paw, while ACC structure was examined by measuring cortical surface and volume. RBF changes and ACC volume were compared between control rats and rats injected with CFA in back muscles segmental (T10) to renal sympathetic innervation or not (T2). In rats with CFA, chronic inflammation was observed in the affected muscles in addition to increased nuclear factor-kappa B (NF-kB) protein expression in corresponding spinal cord segments (p=0.01) as well as decreased ACC volume (p<0.05). In addition, intensity-dependent decreases in RBF during hind paw stimulation were attenuated by chronic pain at T2 (p's<0.05) and T10 (p's<0.05), but less so at T10 compared with T2 (p's<0.05). These results indicate that chronic back pain alters sympathetic functions through non-segmental mechanisms, possibly by altering descending regulatory pathways from ACC. Yet, segmental somato-sympathetic reflexes may compete with non-segmental processes depending on the back region affected by pain and according to the segmental organization of the sympathetic nervous system.
Automated immunohistochemical method to quantify neuronal density in brain sections: application to neuronal loss after status epilepticus.
Journal of neuroscience methods, 2014

To study neurotoxic processes, it is necessary to quantify the number of neurons in a given brain structure and estimate neuronal loss. Neuronal densities can be estimated by immunohistochemical quantitation of a neuronal marker such as the protein NeuN. However, NeuN expression may vary, depending on certain pathophysiological conditions and bias such quantifications.
Waterpipe tobacco smoking prevalence among young people in Great Britain, 2013-2016.
European journal of public health, 2018

One percent of adults in Great Britain use waterpipe tobacco at least monthly, however national epidemiological evidence among young people is absent. This study aims to assess waterpipe tobacco prevalence and correlates among young people in Great Britain.
Astrocytic TDP-43 pathology in Alexander disease.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014

Alexander disease (AxD) is a rare neurodegenerative disorder characterized pathologically by the presence of eosinophilic inclusions known as Rosenthal fibers (RFs) within astrocytes, and is caused by dominant mutations in the coding region of the gene encoding glial fibrillary acidic protein (GFAP). GFAP is the major astrocytic intermediate filament, and in AxD patient brain tissue GFAP is a major component of RFs. TAR DNA binding protein of 43 kDa (TDP-43) is the major pathological protein in almost all cases of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and ∼50% of frontotemporal lobar degeneration (FTLD), designated as FTLD-TDP. In ALS and FTLD-TDP, TDP-43 becomes insoluble, ubiquitinated, and pathologically phosphorylated and accumulates in cytoplasmic inclusions in both neurons and glia of affected brain and spinal cord regions. Previously, TDP-43 was detected in RFs of human pilocytic astrocytomas; however, involvement of TDP-43 in AxD has not been determined. Here we show that TDP-43 is present in RFs in AxD patient brains, and that insoluble phosphorylated full-length and high molecular weight TDP-43 accumulates in white matter of such brains. Phosphorylated TDP-43 also accumulates in the detergent-insoluble fraction from affected brain regions of Gfap(R236H/+) knock-in mice, which harbor a GFAP mutation homologous to one that causes AxD in humans, and TDP-43 colocalizes with astrocytic RF pathology in Gfap(R236H/+) mice and transgenic mice overexpressing human wild-type GFAP. These findings suggest common pathogenic mechanisms in ALS, FTLD, and AxD, and this is the first report of TDP-43 involvement in a neurological disorder primarily affecting astrocytes.
Neuroscience and Values: A Case Study Illustrating Developments in Policy, Training and Research in the UK and Internationally.
Mens sana monographs, 2011

In the current climate of dramatic advances in the neurosciences, it has been widely assumed that the diagnosis of mental disorder is a matter exclusively for value-free science. Starting from a detailed case history, this paper describes how, to the contrary, values come into the diagnosis of mental disorders, directly through the criteria at the heart of psychiatry's most scientifically grounded classification, the American Psychiatric Association's DSM (Diagnostic and Statistical Manual). Various possible interpretations of the prominence of values in psychiatric diagnosis are outlined. Drawing on work in the Oxford analytic tradition of philosophy, it is shown that, properly understood, the prominence of psychiatric diagnostic values reflects the necessary engagement of psychiatry with the diversity of individual human values. This interpretation opens up psychiatric diagnostic assessment to the resources of a new skills-based approach to working with complex and conflicting values (also derived from analytic philosophy) called 'values-based practice.' Developments in values-based practice in training, policy and research in mental health are briefly outlined. The paper concludes with an indication of how the integration of values-based with evidence-based approaches provides the basis for psychiatric practice in the twenty-first century that is both science-based and person-centred.
Neuroscience: waiting for serotonin.
Current biology : CB, 2014

Serotonin dysfunction is implicated in many neuropsychiatric disorders yet the precise behavioral functions of this neuromodulator are not well understood. A new study employs optogenetic methods to activate serotonin neurons during an effort-demanding waiting behavior and demonstrates that serotonin release increases patience, the capacity for self-control.
Neurobiological support to the diagnosis of ADHD in stimulant-naïve adults: pattern recognition analyses of MRI data.
Acta psychiatrica Scandinavica, 2017

In adulthood, the diagnosis of attention-deficit/hyperactivity disorder (ADHD) has been subject of recent controversy. We searched for a neuroanatomical signature associated with ADHD spectrum symptoms in adults by applying, for the first time, machine learning-based pattern classification methods to structural MRI and diffusion tensor imaging (DTI) data obtained from stimulant-naïve adults with childhood-onset ADHD and healthy controls (HC).
Effects of (56)Fe radiation on hippocampal function in mice deficient in chemokine receptor 2 (CCR2).
Behavioural brain research, 2013

(56)Fe irradiation affects hippocampus-dependent cognition. The underlying mechanisms may involve alterations in neurogenesis, expression of the plasticity-related immediate early gene Arc, and inflammation. Chemokine receptor-2 (CCR2), which mediates the recruitment of infiltrating and resident microglia to sites of CNS inflammation, is upregulated by (56)Fe irradiation. CCR2 KO and wild-type mice were used to compare effects of (56)Fe radiation (600MeV, 0.25Gy) on hippocampal function using contextual fear conditioning involving tone shock pairing during training (+/+) and exposure to the same environment without tone shock pairings (-/-). In the -/- condition, irradiation enhanced habituation in WT mice, but not CCR2 KO mice, suggesting that a lack of CCR2 was associated with reduced cognitive performance. In the +/+ condition, irradiation reduced freezing but there was no genotype differences. There were no significant correlations between the number of Arc-positive cells in the dentate gyrus and freezing in either genotype. While measures of neurogenesis and gliogenesis appeared to be modulated by CCR2, there were no effects of genotype on the total numbers of newly born activated microglia before or after irradiation, indicating that other mechanisms are involved in the genotype-dependent radiation response.
Germs are germs, and why not take a risk? Patients' expectations for prescribing antibiotics in an inner-city emergency department.
Medical decision making : an international journal of the Society for Medical Decision Making, 2015

. Extensive use of unnecessary antibiotics has driven the emergence of resistant bacterial strains, posing a threat to public health. Physicians are more likely to prescribe antibiotics when they believe that patients expect them. Current attempts to change these expectations highlight the distinction between viruses and bacteria ("germs are germs"). Fuzzy-trace theory further predicts that patients expect antibiotics because they make decisions based on categorical gist, producing strategies that encourage risk taking when the status quo is bad (i.e., "why not take a risk?"). We investigate both hypotheses.
Potentiation of alpha7 nicotinic acetylcholine receptors via an allosteric transmembrane site.
Proceedings of the National Academy of Sciences of the United States of America, 2008

Positive allosteric modulators of alpha7 nicotinic acetylcholine receptors (nAChRs) have attracted considerable interest as potential tools for the treatment of neurological and psychiatric disorders such as Alzheimer's disease and schizophrenia. However, despite the potential therapeutic usefulness of these compounds, little is known about their mechanism of action. Here, we have examined two allosteric potentiators of alpha7 nAChRs (PNU-120596 and LY-2087101). From studies with a series of subunit chimeras, we have identified the transmembrane regions of alpha7 as being critical in facilitating potentiation of agonist-evoked responses. Furthermore, we have identified five transmembrane amino acids that, when mutated, significantly reduce potentiation of alpha7 nAChRs. The amino acids we have identified are located within the alpha-helical transmembrane domains TM1 (S222 and A225), TM2 (M253), and TM4 (F455 and C459). Mutation of either A225 or M253 individually have particularly profound effects, reducing potentiation of EC(20) concentrations of acetylcholine to a tenth of the level seen with wild-type alpha7. Reference to homology models of the alpha7 nAChR, based on the 4A structure of the Torpedo nAChR, indicates that the side chains of all five amino acids point toward an intrasubunit cavity located between the four alpha-helical transmembrane domains. Computer docking simulations predict that the allosteric compounds such as PNU-120596 and LY-2087101 may bind within this intrasubunit cavity, much as neurosteroids and volatile anesthetics are thought to interact with GABA(A) and glycine receptors. Our findings suggest that this is a conserved modulatory allosteric site within neurotransmitter-gated ion channels.
Cis P-tau underlies vascular contribution to cognitive impairment and dementia and can be effectively targeted by immunotherapy in mice.
Science translational medicine, 2021

Compelling evidence supports vascular contributions to cognitive impairment and dementia (VCID) including Alzheimer's disease (AD), but the underlying pathogenic mechanisms and treatments are not fully understood. Cis P-tau is an early driver of neurodegeneration resulting from traumatic brain injury, but its role in VCID remains unclear. Here, we found robust cis P-tau despite no tau tangles in patients with VCID and in mice modeling key aspects of clinical VCID, likely because of the inhibition of its isomerase Pin1 by DAPK1. Elimination of cis P-tau in VCID mice using cis-targeted immunotherapy, brain-specific Pin1 overexpression, or DAPK1 knockout effectively rescues VCID-like neurodegeneration and cognitive impairment in executive function. Cis mAb also prevents and ameliorates progression of AD-like neurodegeneration and memory loss in mice. Furthermore, single-cell RNA sequencing revealed that young VCID mice display diverse cortical cell type-specific transcriptomic changes resembling old patients with AD, and the vast majority of these global changes were recovered by cis-targeted immunotherapy. Moreover, purified soluble cis P-tau was sufficient to induce progressive neurodegeneration and brain dysfunction by causing axonopathy and conserved transcriptomic signature found in VCID mice and patients with AD with early pathology. Thus, cis P-tau might play a major role in mediating VCID and AD, and antibody targeting it may be useful for early diagnosis, prevention, and treatment of cognitive impairment and dementia after neurovascular insults and in AD.
Information transmission in oscillatory neural activity.
Biological cybernetics, 2008

Periodic neural activity not locked to the stimulus or to motor responses is usually ignored. Here, we present new tools for modeling and quantifying the information transmission based on periodic neural activity that occurs with quasi-random phase relative to the stimulus. We propose a model to reproduce characteristic features of oscillatory spike trains, such as histograms of inter-spike intervals and phase locking of spikes to an oscillatory influence. The proposed model is based on an inhomogeneous Gamma process governed by a density function that is a product of the usual stimulus-dependent rate and a quasi-periodic function. Further, we present an analysis method generalizing the direct method (Rieke et al. in Spikes: exploring the neural code. MIT Press, Cambridge, 1999; Brenner et al. in Neural Comput 12(7):1531-1552, 2000) to assess the information content in such data. We demonstrate these tools on recordings from relay cells in the lateral geniculate nucleus of the cat.
Hippocampal Synaptic Plasticity, Spatial Memory, and Neurotransmitter Receptor Expression Are Profoundly Altered by Gradual Loss of Hearing Ability.
Cerebral cortex (New York, N.Y. : 1991), 2020

Sensory information comprises the substrate from which memories are created. Memories of spatial sensory experience are encoded by means of synaptic plasticity in the hippocampus. Hippocampal dependency on sensory information is highlighted by the fact that sudden and complete loss of a sensory modality results in an impairment of hippocampal function that persists for months. Effects are accompanied by extensive changes in the expression of neurotransmitter receptors in cortex and hippocampus, consistent with a substantial adaptive reorganization of cortical function. Whether gradual sensory loss affects hippocampal function is unclear. Progressive age-dependent hearing loss (presbycusis) is a risk factor for cognitive decline. Here, we scrutinized C57BL/6 mice that experience hereditary and cumulative deafness starting in young adulthood. We observed that 2-4 months postnatally, increases in the cortical and hippocampal expression of GluN2A and GluN2B subunits of the N-methyl-D-aspartate receptor occurred compared to control mice that lack sensory deficits. Furthermore, GABA and metabotropic glutamate receptor expression were significantly altered. Hippocampal synaptic plasticity was profoundly impaired and mice exhibited significant deficits in spatial memory. These data show that during cortical adaptation to cumulative loss of hearing, plasticity-related neurotransmitter expression is extensively altered in the cortex and hippocampus. Furthermore, cumulative sensory loss compromises hippocampal function.
Parkinson's disease advanced therapies - A systematic review: More unanswered questions than guidance.
Parkinsonism & related disorders, 2021

In advanced Parkinson's disease (PD), therapeutic interventions include device-aided therapies such as continuous subcutaneous apomorphine infusion (CSAI), levodopa-carbidopa intestinal gel (LCIG) infusion, and deep brain stimulation (DBS). We reappraised the evidence guiding the decision of appropriate device-aided therapies in advanced PD, and systematically reviewed the literature (including ongoing clinical trials) comparing CSAI, LCIG, DBS in terms of efficacy and cost-effectiveness, with particular consideration to possible conflicts of interests. Of 14,980 documents screened, sixteen were included (4 and 13 studies examining efficacy and cost-effectiveness, respectively). LCIG and DBS showed higher efficacy compared to best medical therapy (BMT). DBS was more expensive than BMT and LCIG. Lifetime costs of CSAI were lower of those of DBS, and DBS lifetime costs were lower than those of LCIG. The majority of studies (11 out of 16) showed direct or indirect sponsorship from pharmaceutical or device companies. Only one ongoing clinical trial comparing LCIG with DBS was found. Device-aided therapies address unmet needs in advanced PD. LCIG and DBS are superior to BMT in head-to-head studies; however, initial and lifetime costs should be considered when choosing those therapies. Guidelines to assist clinicians and patients to choose device-aided therapies, free from conflict of interests, are required.
Establishing zebrafish as a model to study the anxiolytic effects of scopolamine.
Scientific reports, 2017

Scopolamine (hyoscine) is a muscarinic acetylcholine receptor antagonist that has traditionally been used to treat motion sickness in humans. However, studies investigating depressed and bipolar populations have found that scopolamine is also effective at reducing depression and anxiety symptoms. The potential anxiety-reducing (anxiolytic) effects of scopolamine could have great clinical implications for humans; however, rats and mice administered scopolamine showed increased anxiety in standard behavioural tests. This is in direct contrast to findings in humans, and complicates studies to elucidate the specific mechanisms of scopolamine action. The aim of this study was to assess the suitability of zebrafish as a model system to test anxiety-like compounds using scopolamine. Similar to humans, scopolamine acted as an anxiolytic in individual behavioural tests (novel approach test and novel tank diving test). The anxiolytic effect of scopolamine was dose dependent and biphasic, reaching maximum effect at 800 µM. Scopolamine (800 µM) also had an anxiolytic effect in a group behavioural test, as it significantly decreased their tendency to shoal. These results establish zebrafish as a model organism for studying the anxiolytic effects of scopolamine, its mechanisms of action and side effects.
Saccadic delay in multiple sclerosis: A quantitative description.
Vision research, 2020

In multiple sclerosis (MS), eye movement disorders are common and can be quantified with infrared video-oculography. A well-known abnormality is internuclear ophthalmoplegia (INO). This study aims to describe saccadic abnormalities beyond INO and investigate their clinical relevance. A validated standardized infrared oculography protocol, DEMoNS, was used for quantifying saccadic eye movements in three different tasks in MS patients and healthy controls. The relationship between the saccadic parameters and disease characteristics was investigated. Furthermore, the association between saccadic parameters and visual functioning was analysed using logistic regression models, adjusted for possible confounders. This cross-sectional study included 218 subjects with MS and 58 healthy controls. The latency of all saccades was longer in MS patients than in healthy controls. This saccadic delay was larger in subjects with a longer disease duration and more disabled subjects. Furthermore, it was significantly related to presence of a lower vision-related quality of life. This study provided a comprehensive overview of performance of MS patients in different saccadic tasks, compared to healthy controls. Saccadic delay in MS patients was present in all saccadic tasks and was related to advancing disease and visual functioning in daily life.
What makes surgical nerve injury painful? A 4-year to 9-year follow-up of patients with intercostobrachial nerve resection in women treated for breast cancer.
Pain, 2019

Nerve injury during breast cancer surgery can cause neuropathic pain (NP). It is not known why some, but not all, patients develop chronic postsurgical neuropathic pain (CPSNP) after the same nerve injury. In this study, we examined 251 breast cancer survivors with surgeon-verified intercostobrachial nerve resection to identify factors that associate with CPSNP. The patients were recruited from a previous study of 1000 women treated for breast cancer in 2006 to 2010. This enabled us to analyze preoperative factors that associate with future CPSNP. The patients were re-examined in 2014 to 2016 to diagnose CPSNP using the revised NP diagnostic criteria. Preoperative assessments were pain in the area to be operated on, any chronic pain condition, depressive symptoms, anxiety, sleep, and experimental cold pain sensitivity using the cold pressor test (CPT). Follow-up assessments were CPT, psychological factors, sleep, any chronic pain, and basic laboratory tests. One hundred thirty-seven (55%) patients with intercostobrachial nerve resection fulfilled CPSNP diagnostic criteria after 4 to 9 years. Of them, 30 patients (22%) had moderate to severe pain in self-reports and 86 (63%) presented moderate to severe evoked pain at examination. Preoperative pain in the surgical area, other chronic pains, and breast-conserving surgery were associated with future CPSNP. Other chronic pains, increased psychological burden, and insomnia, both before surgery and at the follow-up, were associated with CPSNP. Preoperative CPT did not associate with future CPSNP. Patients with established CPSNP showed increased pain sensitivity in CPT and higher levels of inflammatory markers, suggesting that central sensitization and inflammation may associate with the maintenance of CPSNP.
Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models.
Nature neuroscience, 2012

Mesenchymal stem cells (MSCs) have emerged as a potential therapy for a range of neural insults. In animal models of multiple sclerosis, an autoimmune disease that targets oligodendrocytes and myelin, treatment with human MSCs results in functional improvement that reflects both modulation of the immune response and myelin repair. Here we demonstrate that conditioned medium from human MSCs (MSC-CM) reduces functional deficits in mouse MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) and promotes the development of oligodendrocytes and neurons. Functional assays identified hepatocyte growth factor (HGF) and its primary receptor cMet as critical in MSC-stimulated recovery in EAE, neural cell development and remyelination. Active MSC-CM contained HGF, and exogenously supplied HGF promoted recovery in EAE, whereas cMet and antibodies to HGF blocked the functional recovery mediated by HGF and MSC-CM. Systemic treatment with HGF markedly accelerated remyelination in lysolecithin-induced rat dorsal spinal cord lesions and in slice cultures. Together these data strongly implicate HGF in mediating MSC-stimulated functional recovery in animal models of multiple sclerosis.