rudyvdbrink/CitationDatabase huggingface dataset:
Locomotor Training Promotes Time-dependent Functional Recovery after Experimental Spinal Cord Contusion.
Neuroscience, 2018

Locomotor training (LT) has been exhaustively investigated as a treatment for the spinal cord injury (SCI), however the literature reports both positive and negative effects over the functional recovery. The initiation period of LT following SCI is one of the major variables that needs attention. To investigate the better period, three different starting times were investigated after SCI in rats. Methods: Wistar rats were randomly divided into groups: control, SCI (rats with spinal cord contusion), and SCI groups exposed to LT starting 7, 14 or 28 days after the injury (SCI-T7, SCI-T14 and SCI-T28). LT was performed on a treadmill, five days a week, 20 minutes per day, for ten weeks. Basso, Breattie and Bresnahan (BBB) scale and Horizontal Ladder walking test were used to evaluate the motor function; at the end, morphological and biochemical analyses of the spinal cords, tibialis anterior and soleus muscles were performed. Results: SCI-T14 and SCI-T28 groups had an improvement in both behavioral tests, while SCI-T7 presented a worsening in the functional performance. Late training groups preserved motoneurons in the spinal cord, showed larger muscle fiber areas and higher BDNF expression in tibialis anterior muscle. SCI-T7 group had higher lesion volume after LT in comparison with the SCI group. Late onset of LT promoted an increment of the hindlimb function, while early onset of training worsened the functional recovery of the SCI animals. These results demonstrate a critical LT starting time after the injury, contributing to define the best therapeutic window for rehabilitation.
Diabetes, metformin and cancer risk in myotonic dystrophy type I.
International journal of cancer, 2020

Myotonic dystrophy type I (DM1) is an autosomal dominant multisystem disorder characterized by myotonia and muscle weakness. Type 2 diabetes (T2D) and cancer have been shown to be part of the DM1 phenotype. Metformin, a well-established agent for the management of T2D, is thought to have cancer-preventive effects in the general population. In our study, we aimed to assess the association between T2D, metformin use and the risk of cancer in DM1 patients. We identified a cohort of 913 DM1 patients and an age-, sex- and clinic-matched cohort of 12,318 DM1-free controls from the UK Clinical Practice Research Datalink, a large primary care records database. We used Cox regression models to assess cancer risk in T2D patients who were metformin users or nonusers compared to patients without T2D. Separate analyses were conducted for DM1 patients and controls. T2D was more prevalent in DM1 than in controls (8% vs. 3%, p < 0.0001). DM1 patients with T2D, compared to those without T2D, were more likely to develop cancer (hazard ratio [HR] = 3.60, 95% confidence interval [CI] = 1.18-10.97; p = 0.02), but not if they were treated with metformin (HR = 0.43, 95% CI = 0.06-3.35; p = 0.42). Among controls, we observed no significant associations between T2D and cancer risk in either users or nonusers of Metformin (HR = 1.28, 95% CI = 0.91-1.79; p = 0.16 and HR = 1.13, 95% CI = 0.72-1.79; p = 0.59, respectively). These results show an association between T2D and cancer risk in DM1 patients and may provide new insights into the possible benefits of Metformin use in DM1.
Comparison of sleep complaints and quality of life between patients with neuromyelitis optica spectrum disorder (NMOSD) and healthy controls.
Multiple sclerosis and related disorders, 2019

Neuromyelitis optica spectrum disorder (NMOSD) is a chronic autoimmune disorder which is associated with sleep disturbances and a lower quality of life. The aims of the study were: (1) Comparing sleep characteristics, quality of life, and symptoms of depression and anxiety between patients with NMOSD and healthy controls (HCs). (2) Predicting sleep characteristics among patients with NMOSD based on psychological and illness-related factors.
CSF and Blood Neurofilament Levels in Athletes Participating in Physical Contact Sports: A Systematic Review.
Neurology, 2021

To evaluate whether participating in physical contact sports is associated with a release of neurofilaments and whether such release is related to future clinical neurologic and/or psychiatric impairment.
Hemispheric Asymmetry of Endogenous Neural Oscillations in Young Children: Implications for Hearing Speech In Noise.
Scientific reports, 2016

Speech signals contain information in hierarchical time scales, ranging from short-duration (e.g., phonemes) to long-duration cues (e.g., syllables, prosody). A theoretical framework to understand how the brain processes this hierarchy suggests that hemispheric lateralization enables specialized tracking of acoustic cues at different time scales, with the left and right hemispheres sampling at short (25 ms; 40 Hz) and long (200 ms; 5 Hz) periods, respectively. In adults, both speech-evoked and endogenous cortical rhythms are asymmetrical: low-frequency rhythms predominate in right auditory cortex, and high-frequency rhythms in left auditory cortex. It is unknown, however, whether endogenous resting state oscillations are similarly lateralized in children. We investigated cortical oscillations in children (3-5 years; N = 65) at rest and tested our hypotheses that this temporal asymmetry is evident early in life and facilitates recognition of speech in noise. We found a systematic pattern of increasing leftward asymmetry for higher frequency oscillations; this pattern was more pronounced in children who better perceived words in noise. The observed connection between left-biased cortical oscillations in phoneme-relevant frequencies and speech-in-noise perception suggests hemispheric specialization of endogenous oscillatory activity may support speech processing in challenging listening environments, and that this infrastructure is present during early childhood.
Differential involvement of striato- and cerebello-thalamo-cortical pathways in tremor- and akinetic/rigid-predominant Parkinson's disease.
Neuroscience, 2011

Parkinson's disease (PD) presents clinically with varying degrees of resting tremor, rigidity, and bradykinesia. For decades, striatal-thalamo-cortical (STC) dysfunction has been implied in bradykinesia and rigidity, but does not explain resting tremor in PD. To understand the roles of cerebello-thalamo-cortical (CTC) and STC circuits in the pathophysiology of the heterogeneous clinical presentation of PD, we collected functional magnetic resonance imaging (fMRI) data from 17 right-handed PD patients [nine tremor predominant (PDT) and eight akinetic-rigidity predominant (PDAR)] and 14 right-handed controls while they performed internally-guided (IG) sequential finger tapping tasks. The percentage of voxels activated in regions constituting the STC and CTC [divided as cerebellar hemisphere-thalamo-cortical (CHTC) and vermis-thalamo-cortical (CVTC)] circuits was calculated. Multivariate analysis of variance compared the activation patterns of these circuits between study groups. Compared to controls, both PDAR and PDT subjects displayed an overall increase in the percentage of voxels activated in both STC and CTC circuits. These increases reached statistical significance in contralateral STC and CTC circuits for PDT subjects, and in contralateral CTC pathways for PDAR subjects. Comparison of PDAR and PDT subjects revealed significant differences in ipsilateral STC (P=0.005) and CTC (P=0.043 for CHTC and P=0.003 for CVTC) circuits. These data support the differential involvement of STC and CTC circuits in PD subtypes, and help explain the heterogeneous presentation of PD symptoms. These findings underscore the importance of integrating CTC circuits in understanding PD and other disorders of the basal ganglia.
Alterations of functional properties of hippocampal networks following repetitive closed-head injury.
Experimental neurology, 2016

Traumatic brain injury (TBI) is the leading cause of death for persons under the age of 45. Military service members who have served on multiple combat deployments and contact-sport athletes are at particular risk of sustaining repetitive TBI (rTBI). Cognitive and behavioral deficits resulting from rTBI are well documented. Optimal associative LTP, occurring in the CA1 hippocampal Schaffer collateral pathway, is required for both memory formation and retrieval. Surprisingly, ipsilateral Schaffer collateral CA1 LTP evoked by 100 Hz tetanus was enhanced in mice from the 3× closed head injury (3× CHI) treatment group in comparison to LTP in contralateral or 3× Sham CA1 area, and in spite of reduced freezing during contextual fear conditioning at one week following 3× CHI. Electrophysiological activity of CA1 neurons was evaluated with whole-cell patch-clamp recordings. 3× CHI ipsilateral CA1 neurons exhibited significant increases in action potential amplitude and maximum rise and decay slope while the action potential duration was decreased. Recordings of CA1 neuron postsynaptic currents were conducted to detect spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs/sIPSCs) and respective miniature currents (mEPSCs and mIPSCs). In the 3× CHI mice, sEPSCs and sIPSCs in ipsilateral CA1 neurons had an increased frequency of events but decreased amplitudes. In addition, 3× CHI altered the action potential-independent miniature postsynaptic currents. The mEPSCs of ipsilateral CA1 neurons exhibited both an increased frequency of events and larger amplitudes. Moreover, the effect of 3× CHI on mIPSCs was opposite to that of the sIPSCs. Specifically, the frequency of the mIPSCs was decreased while the amplitudes were increased. These results are consistent with a mechanism in which repetitive closed-head injury affects CA1 hippocampal function by promoting a remodeling of excitatory and inhibitory synaptic inputs leading to impairment in hippocampal-dependent tasks.
Validation of antibody-based tools for galanin research.
Peptides, 2019

Antibodies are an integral biomedical tool, not only for research but also as therapeutic agents. However, progress can only be made with sensitive and specific antibodies. The regulatory (neuro)peptide galanin and its three endogenous receptors (GAL
HMG-CoA reductase inhibitor rosuvastatin improves abnormal brain electrical activity via mechanisms involving eNOS.
Neuroscience, 2015

Apart from its repressing effect on plasma lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors exert neuroprotective functions in animal models of neurodegenerative disorders. In view of these promising observations, we were interested in whether HMG-CoA reductase inhibition would affect epileptiform activity in the brain. To elucidate this issue, atorvastatin, simvastatin and rosuvastatin were administered orally at a dose of 20 mg/kg each for 3 days and their anti-epileptic activities were tested and compared in rats. Epileptiform activity in the brain was induced by an intracortical penicillin G injection. Among HMG-CoA reductase inhibitors, simvastatin-treatment was less effective in terms of spike frequency as compared with atorvastatin- and rosuvastatin-treated animals. Atorvastatin treatment reduced spike frequencies and amplitudes significantly throughout the experiment. However, the most pronounced anti-epileptic effect was observed in rosuvastatin-treated animals, which was associated with improved blood-brain barrier (BBB) integrity, increased expression of endothelial nitric oxide synthase (eNOS) mRNA and decreased expressions of pro-apoptotic p53, Bax and caspase-3 mRNAs. Inhibition of eNOS activity with L-NG-Nitroarginine Methyl Ester (L-NAME) reversed the anti-epileptic effect of rosuvastatin significantly. However, L-NAME did not alter the effect of rosuvastatin on the levels of p53, Bax and caspase-3 mRNA expression. Here, we provide evidence that among HMG-CoA reductase inhibitors, rosuvastatin was the most effective statin on the reduction of epileptiform activity, which was associated with improved BBB permeability, increased expression of eNOS and decreased expressions of pro-apoptotic p53, Bax and caspase-3. Our observation also revealed that the anti-epileptic effect of rosuvastatin was dependent on the increased expression level of eNOS. The robust anti-epileptic effect encourages proof-of-concept studies with rosuvastatin in human epilepsy patients with hypercholesterolemia.
Selectively reduced contrast sensitivity in high schizotypy.
Experimental brain research, 2020

Deficits in the ability to encode small differences in contrast between adjacent parts of an image (contrast sensitivity) are well documented in schizophrenic patients. In the present study, we sought to determine whether contrast sensitivity deficits reported in schizophrenic patients are also evident in those who exhibit high schizotypy scores in a typical (i.e., non-schizophrenic) population. Using the O-Life Questionnaire, we determined the effects of schizotypy on spatial (0.5, 2 and 8 c/deg) and spatiotemporal (0.5 and 8 c/deg at 0.5 and 8 Hz) contrast sensitivity in 73 young (18-26 years), majority female (n = 68) participants. We found differences in contrast sensitivity that were spatial, spatiotemporal and O-Life subscale specific. Spatial contrast sensitivity was significantly lower in high, compared to low schizotypes at low spatial frequencies (0.5 c/deg) in those who scored highly on the Unusual Experiences and Cognitive Disorganisation O-Life subscales. For moving stimuli, individuals with high scores on the Unusual Experiences subscale exhibited lower spatiotemporal contrast sensitivity for 0.5 and 8 c/deg patterns drifting at 8 Hz. Although the effects reported here were relatively small, this is the first report of reduced contrast sensitivity in schizotypy.
Optimization of potency and pharmacokinetic properties of tetrahydroisoquinoline transient receptor potential melastatin 8 (TRPM8) antagonists.
Journal of medicinal chemistry, 2014

Transient receptor potential melastatin 8 (TRPM8) is a nonselective cation channel expressed in a subpopulation of sensory neurons in the peripheral nervous system. TRPM8 is the predominant mammalian cold temperature thermosensor and is activated by cold temperatures ranging from 8 to 25 °C and cooling compounds such as menthol or icilin. TRPM8 antagonists are being pursued as potential therapeutics for treatment of pain and bladder disorders. This manuscript outlines new developments in the SAR of a lead series of 1,2,3,4-tetrahydroisoquinoline derivatives with emphasis on strategies to improve pharmacokinetic properties and potency. Selected compounds were profiled in two TRPM8 target-specific in vivo coverage models in rats (the icilin-induced wet dog shake model and the cold pressor test). Compound 45 demonstrated robust efficacy in both pharmacodynamic models with ED90 values <3 mg/kg.
Calpain inhibitor attenuated optic nerve damage in acute optic neuritis in rats.
Journal of neurochemistry, 2013

Optic neuritis (ON), which is an acute inflammatory autoimmune demyelinating disease of the central nervous system (CNS), often occurs in multiple sclerosis (MS). ON is an early diagnostic sign in most MS patients caused by damage to the optic nerve leading to visual dysfunction. Various features of both MS and ON can be studied following induction of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, in Lewis rats. Inflammation and cell death in the optic nerve, with subsequent damage to the retinal ganglion cells in the retina, are thought to correlate with visual dysfunction. Thus, characterizing the pathophysiological changes that lead to visual dysfunction in EAE animals may help develop novel targets for therapeutic intervention. We treated EAE animals with and without the calpain inhibitor calpeptin (CP). Our studies demonstrated that the Ca(2+)-activated neutral protease calpain was upregulated in the optic nerve following induction of EAE at the onset of clinical signs (OCS) of the disease, and these changes were attenuated following treatment with CP. These reductions correlated with decreases in inflammation (cytokines, iNOS, COX-2, and NF-κB), and microgliosis (i.e. activated microglia). We observed that calpain inhibition reduced astrogliosis (reactive astroglia) and expression of aquaporin 4 (AQP4). The balance of Th1/Th2 cytokine production and also expression of the Th1-related CCR5 and CXCR3 chemokine receptors influence many pathological processes and play both causative and protective roles in neuron damage. Our data indicated that CP suppressed cytokine imbalances. Also, Bax:Bcl-2 ratio, production of tBid, PARP-1, expression and activities of calpain and caspases, and internucleosomal DNA fragmentation were attenuated after treatment with CP. Our results demonstrated that CP decreased demyelination [loss of myelin basic protein (MBP)] and axonal damage [increase in dephosphorylated neurofilament protein (de-NFP)], and also promoted intracellular neuroprotective pathways in optic nerve in EAE rats. Thus, these data suggest that calpain is involved in inflammatory as well as in neurodegenerative aspects of the disease and may be a promising target for treating ON in EAE and MS.
Mood-related central and peripheral clocks.
The European journal of neuroscience, 2020

Mood disorders, including major depression, bipolar disorder, and seasonal affective disorder, are debilitating disorders that affect a significant portion of the global population. Individuals suffering from mood disorders often show significant disturbances in circadian rhythms and sleep. Moreover, environmental disruptions to circadian rhythms can precipitate or exacerbate mood symptoms in vulnerable individuals. Circadian clocks exist throughout the central nervous system and periphery, where they regulate a wide variety of physiological processes implicated in mood regulation. These processes include monoaminergic and glutamatergic transmission, hypothalamic-pituitary-adrenal axis function, metabolism, and immune function. While there seems to be a clear link between circadian rhythm disruption and mood regulation, the mechanisms that underlie this association remain unclear. This review will touch on the interactions between the circadian system and each of these processes and discuss their potential role in the development of mood disorders. While clinical studies are presented, much of the review will focus on studies in animal models, which are attempting to elucidate the molecular and cellular mechanisms in which circadian genes regulate mood.
Overground walking patterns after chronic incomplete spinal cord injury show distinct response patterns to unloading.
Journal of neuroengineering and rehabilitation, 2018

Body weight support (BWS) is often provided to incomplete spinal cord injury (iSCI) patients during rehabilitation to enable gait training before full weight-bearing is recovered. Emerging robotic devices enable BWS during overground walking, increasing task-specificity of the locomotor training. However, in contrast to a treadmill setting, there is little information on how unloading is integrated into overground locomotion. We investigated the effect of a transparent multi-directional BWS system on overground walking patterns at different levels of unloading in individuals with chronic iSCI (CiSCI) compared to controls.
The subfornical organ in sodium appetite: Recent insights.
Neuropharmacology, 2019

To maintain sodium homeostasis, animals will readily seek and ingest salt when salt-depleted, even at concentrations that they typically find aversive when sodium replete. This innate behaviour is known as sodium (or salt) appetite. Salt appetite is subserved by a conserved brain network that senses sodium need and promotes the ingestion of salty substances when sodium-deficient. The subfornical organ (SFO) is a circumventricular organ that has diverse roles encompassing cardiovascular regulation, energy balance, immune responses, reproduction, and hydromineral balance. The SFO acts as a central sensor of sodium need and is essential for the generation of salt appetite. In this review, we discuss recent findings on the neurochemical and circuit-level organisation of the SFO in the context of sodium appetite. This article is part of the Special Issue entitled 'Hypothalamic Control of Homeostasis'.
How great is the negative impact of masking and social distancing and how can we enhance communication skills in the elderly people?
Aging clinical and experimental research, 2021

During COVID-19 pandemic, protective measures such as social distancing and face masks posed a challenge in daily communication, in this context the elderly are one of the most at risk categories as widely exposed to hearing loss. This article focuses on how the COVID-19 pandemic affected verbal communication, especially on those people that even in normal conditions present an increased difficulty in speech perception. Special attention has been paid to hearing aids and cochlear implant users, these devices indeed can be affected by a speech intelligibility reduction and could be uncomfortable if used together with face masks. Possible alternatives and solutions will be proposed to reduce the negative impacts of face coverings on communication, to enhance speech intelligibility and to manage wearability of hearing rehabilitation devices.
Intrinsic functional neuron-type selectivity of transcranial focused ultrasound neuromodulation.
Nature communications, 2021

Transcranial focused ultrasound (tFUS) is a promising neuromodulation technique, but its mechanisms remain unclear. We hypothesize that if tFUS parameters exhibit distinct modulation effects in different neuron populations, then the mechanism can be understood through identifying unique features in these neuron populations. In this work, we investigate the effect of tFUS stimulation on different functional neuron types in in vivo anesthetized rodent brains. Single neuron recordings were separated into regular-spiking and fast-spiking units based on their extracellular spike shapes acquired through intracranial electrophysiological recordings, and further validated in transgenic optogenetic mice models of light-excitable excitatory and inhibitory neurons. We show that excitatory and inhibitory neurons are intrinsically different in response to ultrasound pulse repetition frequency (PRF). The results suggest that we can preferentially target specific neuron types noninvasively by tuning the tFUS PRF. Chemically deafened rats and genetically deafened mice were further tested for validating the directly local neural effects induced by tFUS without potential auditory confounds.