rudyvdbrink/CitationDatabase huggingface dataset:
GABAergic synaptic transmission triggers action potentials in thalamic reticular nucleus neurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

GABAergic neurons in the thalamic reticular nucleus (TRN) form powerful inhibitory connections with several dorsal thalamic nuclei, thereby controlling attention, sensory processing, and synchronous oscillations in the thalamocortical system. TRN neurons are interconnected by a network of GABAergic synapses, but their properties and their role in shaping TRN neuronal activity are not well understood. Using recording techniques aimed to minimize changes in the intracellular milieu, we show that synaptic GABA(A) receptor activation triggers postsynaptic depolarizations in mouse TRN neurons. Immunohistochemical data indicate that TRN neurons express very low levels of the Cl(-) transporter KCC2. In agreement, perforated-patch recordings show that intracellular Cl(-) levels are high in TRN neurons, resulting in a Cl(-) reversal potential (E(Cl)) significantly depolarized from rest. Additionally, we find that GABA(A) receptor-evoked depolarizations are amplified by the activation of postsynaptic T-type Ca(2+) channels, leading to dendritic Ca(2+) increases and the generation of burst firing in TRN neurons. In turn, GABA-evoked burst firing results in delayed and long-lasting feedforward inhibition in thalamic relay cells. Our results show that GABA-evoked depolarizations can interact with T-type Ca(2+) channels to powerfully control spike generation in TRN neurons.
Long-term surgical results of supplementary motor area epilepsy surgery.
Journal of neurosurgery, 2017

OBJECTIVE Supplementary motor area (SMA) epilepsy is a well-known clinical condition; however, long-term surgical outcome reports are scarce and correspond to small series or isolated case reports. The aim of this study is to present the surgical results of SMA epilepsy patients treated at 2 reference centers in Mexico City. METHODS For this retrospective descriptive study (1999-2014), 52 patients underwent lesionectomy and/or corticectomy of the SMA that was guided by electrocorticography (ECoG). The clinical, neurophysiological, neuroimaging, and pathological findings are described. The Engel scale was used to classify surgical outcome. Descriptive statistics, Student t-test, and Friedman, Kruskal-Wallis, and chi-square tests were used. RESULTS Of these 52 patients, the mean age at epilepsy onset was 26.3 years, and the mean preoperative seizure frequency was 14 seizures per month. Etiologies included low-grade tumors in 28 (53.8%) patients, cortical dysplasia in 17 (32.7%) patients, and cavernomas in 7 (13.5%) patients. At a mean follow-up of 5.7 years (range 1-10 years), 32 patients (61%) were classified as Engel Class I, 16 patients (31%) were classified as Engel Class II, and 4 (8%) patients were classified as Engel Class III. Overall seizure reduction was significant (p = 0.001). The absence of early postsurgical seizures and lesional etiology were associated with the outcome of Engel Class I (p = 0.05). Twenty-six (50%) patients had complications in the immediate postoperative period, all of which resolved completely with no residual neurological deficits. CONCLUSIONS Surgery for SMA epilepsy guided by ECoG using a multidisciplinary and multimodality approach is a safe, feasible procedure that shows good seizure control, moderate morbidity, and no mortality.
The role of aldehyde oxidase and xanthine oxidase in the biotransformation of a novel negative allosteric modulator of metabotropic glutamate receptor subtype 5.
Drug metabolism and disposition: the biological fate of chemicals, 2012

Negative allosteric modulation (NAM) of metabotropic glutamate receptor subtype 5 (mGlu₅) represents a therapeutic strategy for the treatment of childhood developmental disorders, such as fragile X syndrome and autism. VU0409106 emerged as a lead compound within a biaryl ether series, displaying potent and selective inhibition of mGlu₅. Despite its high clearance and short half-life, VU0409106 demonstrated efficacy in rodent models of anxiety after extravascular administration. However, lack of a consistent correlation in rat between in vitro hepatic clearance and in vivo plasma clearance for the biaryl ether series prompted an investigation into the biotransformation of VU0409106 using hepatic subcellular fractions. An in vitro appraisal in rat, monkey, and human liver S9 fractions indicated that the principal pathway was NADPH-independent oxidation to metabolite M1 (+16 Da). Both raloxifene (aldehyde oxidase inhibitor) and allopurinol (xanthine oxidase inhibitor) attenuated the formation of M1, thus implicating the contribution of both molybdenum hydroxylases in the biotransformation of VU0409106. The use of ¹⁸O-labeled water in the S9 experiments confirmed the hydroxylase mechanism proposed, because ¹⁸O was incorporated into M1 (+18 Da) as well as in a secondary metabolite (M2; +36 Da), the formation of which was exclusively xanthine oxidase-mediated. This unusual dual and sequential hydroxylase metabolism was confirmed in liver S9 and hepatocytes of multiple species and correlated with in vivo data because M1 and M2 were the principal metabolites detected in rats administered VU0409106. An in vitro-in vivo correlation of predicted hepatic and plasma clearance was subsequently established for VU0409106 in rats and nonhuman primates.
Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults.
The Cochrane database of systematic reviews, 2013

This is an updated version of the original Cochrane review published in Issue 11, 2010 (Derry 2010). Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting, which are commonly associated with migraine.
Low incidence of symptomatic strokes after carotid stenting without embolization protection devices for extracranial carotid stenosis: a single-institution retrospective review.
Neurosurgery, 2008

Carotid angioplasty and stenting (CAS) remains the primary modality of treating individuals with carotid stenosis and significant comorbidities or anatomically difficult lesions. The use of embolization protection devices (EPD) has been mandated by the cerebrovascular community even though the ability of these devices to prevent symptomatic strokes is not supported by the current literature. Our goal was to assess the clinical and radiological outcomes of patients who underwent CAS without EPDs at our hospital from 1996 to 2006.
Association between serum levels of glial cell-line derived neurotrophic factor and attention deficits in schizophrenia.
Neuroscience letters, 2014

Several lines of evidence suggest that glial cell-line derived neurotrophic factor (GDNF) plays an important role in the pathophysiology of neuropsychiatric and neurodegenerative disorders. In this study, we investigated the association between GDNF serum levels and the clinical status of medicated patients with schizophrenia. Sixty-three medicated patients with schizophrenia and 52 age- and sex-matched healthy controls were recruited. Patients were evaluated using the brief psychiatry rating scale, the scale for the assessment of negative symptoms (SANS) and neuropsychological tests. Serum levels of GDNF were determined using an ELISA method. Serum levels of GDNF did not differ between schizophrenia patients and controls. Higher GDNF serum levels were associated with better performances on the Digit Span in healthy controls but not in schizophrenics. At the same time, higher GDNF serum levels were associated with severe attention deficits on the SANS subscale, in schizophrenics. Our preliminary study suggests that serum levels of GDNF may be an unsuitable biomarker for schizophrenia, although it may be associated with working memory in healthy controls and the pathophysiology of attention deficits in schizophrenia.
Blended-Learning Pain Neuroscience Education for People With Chronic Spinal Pain: Randomized Controlled Multicenter Trial.
Physical therapy, 2018

Available evidence favors the use of pain neuroscience education (PNE) in patients with chronic pain. However, PNE trials are often limited to small sample sizes and, despite the current digital era, the effects of blended-learning PNE (ie, the combination of online digital media with traditional educational methods) have not yet been investigated.
Sarcopenic obesity and associations with mortality in older women and men - a prospective observational study.
BMC geriatrics, 2020

The combined effect of sarcopenia and obesity, i.e., sarcopenic obesity, has been associated with disability and worse outcomes in older adults, but results are conflicting. The objectives of this study were to describe the prevalence of sarcopenic obesity (SO) in older adults, and to examine how the risk of mortality is associated with SO and its various components.
Increased levels of intramuscular cytokines in patients with jaw muscle pain.
The journal of headache and pain, 2017

The aim of this study was to investigate cytokine levels in the masseter muscle, their response to experimental tooth-clenching and their relation to pain, fatigue and psychological distress in patients with temporomandibular disorders (TMD) myalgia.
How Is Adolescent Bone Mass and Density Influenced by Early Life Body Size and Growth? The Tromsø Study: Fit Futures-A Longitudinal Cohort Study From Norway.
JBMR plus, 2018

The effect of birth weight and childhood body mass index (BMI) on adolescents' bone parameters is not established. The aim of this longitudinal, population-based study was to investigate the association of birth weight, childhood BMI, and growth, with adolescent bone mass and bone density in a sample of 633 adolescents (48% girls) from The Tromsø Study: Fit Futures. This population-based cohort study was conducted in 2010-2011 and 2012-2013 in Tromsø, Norway. Bone mineral content (BMC) and areal BMD (aBMD) were measured at total hip (TH) and total body (TB) by dual-energy X-ray absorptiometry (DXA) and converted to internal
Functional magnetic resonance imaging (fMRI) item analysis of empathy and theory of mind.
Human brain mapping, 2020

In contrast to conventional functional magnetic resonance imaging (fMRI) analysis across participants, item analysis allows generalizing the observed neural response patterns from a specific stimulus set to the entire population of stimuli. In the present study, we perform an item analysis on an fMRI paradigm (EmpaToM) that measures the neural correlates of empathy and Theory of Mind (ToM). The task includes a large stimulus set (240 emotional vs. neutral videos to probe empathic responding and 240 ToM or factual reasoning questions to probe ToM), which we tested in two large participant samples (N = 178, N = 130). Both, the empathy-related network comprising anterior insula, anterior cingulate/dorsomedial prefrontal cortex, inferior frontal gyrus, and dorsal temporoparietal junction/supramarginal gyrus (TPJ) and the ToM related network including ventral TPJ, superior temporal gyrus, temporal poles, and anterior and posterior midline regions, were observed across participants and items. Regression analyses confirmed that these activations are predicted by the empathy or ToM condition of the stimuli, but not by low-level features such as video length, number of words, syllables or syntactic complexity. The item analysis also allowed for the selection of the most effective items to create optimized stimulus sets that provide the most stable and reproducible results. Finally, reproducibility was shown in the replication of all analyses in the second participant sample. The data demonstrate (a) the generalizability of empathy and ToM related neural activity and (b) the reproducibility of the EmpaToM task and its applicability in intervention and clinical imaging studies.
Design and Synthesis of 2,3- trans-Proline Analogues as Ligands for Ionotropic Glutamate Receptors and Excitatory Amino Acid Transporters.
ACS chemical neuroscience, 2019

Development of pharmacological tools for the ionotropic glutamate receptors (iGluRs) is imperative for the study and understanding of the role and function of these receptors in the central nervous system. We report the synthesis of 18 analogues of (2 S,3 R)-2-carboxy-3-pyrrolidine acetic acid (3a), which explores the effect of introducing a substituent on the ε-carbon (3c-q). A new synthetic method was developed for the efficient synthesis of racemic 3a and applied to give expedited access to 13 racemic analogues of 3a. Pharmacological characterization was carried out at native iGluRs, cloned homomeric kainate receptors (GluK1-3), NMDA receptors (GluN1/GluN2A-D), and excitatory amino acid transporters (EAAT1-3). From the structure-activity relationship studies, several new ligands emerged, exemplified by triazole 3p-d1, GluK3-preferring (GluK1/GluK3 K
Dim light at night disturbs the daily sleep-wake cycle in the rat.
Scientific reports, 2016

Exposure to light at night (LAN) is associated with insomnia in humans. Light provides the main input to the master clock in the hypothalamic suprachiasmatic nucleus (SCN) that coordinates the sleep-wake cycle. We aimed to develop a rodent model for the effects of LAN on sleep. Therefore, we exposed male Wistar rats to either a 12 h light (150-200lux):12 h dark (LD) schedule or a 12 h light (150-200 lux):12 h dim white light (5 lux) (LDim) schedule. LDim acutely decreased the amplitude of daily rhythms of REM and NREM sleep, with a further decrease over the following days. LDim diminished the rhythms of 1) the circadian 16-19 Hz frequency domain within the NREM sleep EEG, and 2) SCN clock gene expression. LDim also induced internal desynchronization in locomotor activity by introducing a free running rhythm with a period of ~25 h next to the entrained 24 h rhythm. LDim did not affect body weight or glucose tolerance. In conclusion, we introduce the first rodent model for disturbed circadian control of sleep due to LAN. We show that internal desynchronization is possible in a 24 h L:D cycle which suggests that a similar desynchronization may explain the association between LAN and human insomnia.
Metabolic Alterations in Developing Brain After Injury: Knowns and Unknowns.
Neurochemical research, 2015

Brain development is a highly orchestrated complex process. The developing brain utilizes many substrates including glucose, ketone bodies, lactate, fatty acids and amino acids for energy, cell division and the biosynthesis of nucleotides, proteins and lipids. Metabolism is crucial to provide energy for all cellular processes required for brain development and function including ATP formation, synaptogenesis, synthesis, release and uptake of neurotransmitters, maintaining ionic gradients and redox status, and myelination. The rapidly growing population of infants and children with neurodevelopmental and cognitive impairments and life-long disability resulting from developmental brain injury is a significant public health concern. Brain injury in infants and children can have devastating effects because the injury is superimposed on the high metabolic demands of the developing brain. Acute injury in the pediatric brain can derail, halt or lead to dysregulation of the complex and highly regulated normal developmental processes. This paper provides a brief review of metabolism in developing brain and alterations found clinically and in animal models of developmental brain injury. The metabolic changes observed in three major categories of injury that can result in life-long cognitive and neurological disabilities, including neonatal hypoxia-ischemia, pediatric traumatic brain injury, and brain injury secondary to prematurity are reviewed.
Surgical incision can alter capsaicin-induced central sensitization in rat brainstem nociceptive neurons.
Neuroscience, 2008

Surgical trauma can affect spinal neuronal excitability, but there have been no studies of the effects of surgical cutaneous injury on central nociceptive processing of deep afferent inputs evoked by noxious stimuli such as capsaicin. Thus our aim was to test the effect of surgical cutaneous incision in influencing central sensitization induced by capsaicin injection into the temporomandibular joint (TMJ). The activity of single nociceptive neurons activated by noxious mechanical stimulation of the TMJ was recorded in the trigeminal subnucleus caudalis/upper cervical cord of halothane-anesthetized rats. The cutaneous mechanoreceptive field (RF), cutaneous mechanical activation threshold (MAT) and TMJ MAT of neurons before and after both surgical cutaneous incision alone and capsaicin injection were compared with results of incision and lidocaine pretreatment of the facial skin overlying the TMJ and capsaicin injection into the TMJ. Incision itself induced a barrage of neuronal spikes and excitability increases reflecting central sensitization (cutaneous RF expansion, cutaneous MAT reduction) in most neurons tested whereas lidocaine pretreatment significantly attenuated the barrage and central sensitization. Capsaicin injection into the TMJ induced cutaneous RF expansion, cutaneous MAT reduction and TMJ MAT reduction following lidocaine pretreatment of the cutaneous incision site whereas capsaicin injection following incision alone not only failed to induce further central sensitization but also decreased the existing incision-induced central sensitization (no cutaneous RF expansion, increased cutaneous MAT and TMJ MAT) in most neurons tested. These findings suggest that central sensitization induced by capsaicin alone or by cutaneous incision alone can readily occur in TMJ-responsive nociceptive neurons and that following incision-induced excitability increases, capsaicin may result in a temporary suppression of nociceptive neuronal changes reflecting central sensitization.
D-Cycloserine Augmentation of Exposure-Based Cognitive Behavior Therapy for Anxiety, Obsessive-Compulsive, and Posttraumatic Stress Disorders: A Systematic Review and Meta-analysis of Individual Participant Data.
JAMA psychiatry, 2017

Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear.
Palmitic acid methyl ester inhibits cardiac arrest-induced neuroinflammation and mitochondrial dysfunction.
Prostaglandins, leukotrienes, and essential fatty acids, 2021

We previously discovered that palmitic acid methyl ester (PAME) is a potent vasodilator released from the sympathetic ganglion with vasoactive properties. Post-treatment with PAME can enhance cortical cerebral blood flow and functional learning and memory, while inhibiting neuronal cell death in the CA1 region of the hippocampus under pathological conditions (i.e. cerebral ischemia). Since mechanisms underlying PAME-mediated neuroprotection remain unclear, we investigated the possible neuroprotective mechanisms of PAME after 6 min of asphyxial cardiac arrest (ACA, an animal model of global cerebral ischemia). Our results from capillary-based immunoassay (for the detection of proteins) and cytokine array suggest that PAME (0.02 mg/kg) can decrease neuroinflammatory markers, such as ionized calcium binding adaptor molecule 1 (Iba1, a specific marker for microglia/macrophage activation) and inflammatory cytokines after cardiopulmonary resuscitation. Additionally, the mitochondrial oxygen consumption rate (OCR) and respiratory function in the hippocampal slices were restored following ACA (via Seahorse XF24 Extracellular Flux Analyzer) suggesting that PAME can ameliorate mitochondrial dysfunction. Finally, hippocampal protein arginine methyltransferase 1 (PRMT1) and PRMT8 are enhanced in the presence of PAME to suggest a possible pathway of methylated fatty acids to modulate arginine-based enzymatic methylation. Altogether, our findings suggest that PAME can provide neuroprotection in the presence of ACA to alleviate neuroinflammation and ameliorate mitochondrial dysfunction.
The bradykinin system in stress and anxiety in humans and mice.
Scientific reports, 2019

Pharmacological research in mice and human genetic analyses suggest that the kallikrein-kinin system (KKS) may regulate anxiety. We examined the role of the KKS in anxiety and stress in both species. In human genetic association analysis, variants in genes for the bradykinin precursor (KNG1) and the bradykinin receptors (BDKRB1 and BDKRB2) were associated with anxiety disorders (p < 0.05). In mice, however, neither acute nor chronic stress affected B1 receptor gene or protein expression, and B1 receptor antagonists had no effect on anxiety tests measuring approach-avoidance conflict. We thus focused on the B2 receptor and found that mice injected with the B2 antagonist WIN 64338 had lowered levels of a physiological anxiety measure, the stress-induced hyperthermia (SIH), vs controls. In the brown adipose tissue, a major thermoregulator, WIN 64338 increased expression of the mitochondrial regulator Pgc1a and the bradykinin precursor gene Kng2 was upregulated after cold stress. Our data suggests that the bradykinin system modulates a variety of stress responses through B2 receptor-mediated effects, but systemic antagonists of the B2 receptor were not anxiolytic in mice. Genetic variants in the bradykinin receptor genes may predispose to anxiety disorders in humans by affecting their function.
Magnetic resonance imaging in the evaluation of cognitive function.
Pediatric blood & cancer, 2014

Image quality of magnetic resonance imaging (MRI) scans of the brain currently approximate gross anatomy as would be viewed at autopsy. During the first decade of the 21st Century incredible advances in image processing and quantification have occurred permitting more refined methods for studying brain-behavior-cognitive functioning. The current presentation overviews the current status of MRI methods for routine clinical assessment of brain pathology, how these techniques identify neuropathology and how pathological findings are quantified. Diffusion tensor imaging (DTI), functional MRI (fMRI), and resting state fMRI are all reviewed, emphasizing how these techniques permit an examination of brain function and connectivity. General regional relationships of brain function associated with cognitive control will be highlighted.
Predictors of violent behavior among acute psychiatric patients: clinical study.
Psychiatry and clinical neurosciences, 2008

Violence risk prediction is a priority issue for clinicians working with mentally disordered offenders. The aim of the present study was to determine violence risk factors in acute psychiatric inpatients.