rudyvdbrink/CitationDatabase huggingface dataset:
AMPK induces regulatory innate lymphoid cells after traumatic brain injury.
JCI insight, 2021

The CNS is regarded as an immunoprivileged organ, evading routine immune surveillance; however, the coordinated development of immune responses profoundly influences outcomes after brain injury. Innate lymphoid cells (ILCs) are cytokine-producing cells that are critical for the initiation, modulation, and resolution of inflammation, but the functional relevance and mechanistic regulation of ILCs are unexplored after acute brain injury. We demonstrate increased proliferation of all ILC subtypes within the meninges for up to 1 year after experimental traumatic brain injury (TBI) while ILCs were present within resected dura and elevated within cerebrospinal fluid (CSF) of moderate-to-severe TBI patients. In line with energetic derangements after TBI, inhibition of the metabolic regulator, AMPK, increased meningeal ILC expansion, whereas AMPK activation suppressed proinflammatory ILC1/ILC3 and increased the frequency of IL-10-expressing ILC2 after TBI. Moreover, intracisternal administration of IL-33 activated AMPK, expanded ILC2, and suppressed ILC1 and ILC3 within the meninges of WT and Rag1-/- mice, but not Rag1-/- IL2rg-/- mice. Taken together, we identify AMPK as a brake on the expansion of proinflammatory, CNS-resident ILCs after brain injury. These findings establish a mechanistic framework whereby immunometabolic modulation of ILCs may direct the specificity, timing, and magnitude of cerebral immunity.
One Cycle Fuels Another: The Energetics of Neurotransmitter Release.
Neuron, 2017

In this issue of Neuron, Ashrafi et al. (2017) show that activity induces translocation of the insulin-regulated glucose transporter GLUT4 to the plasma membrane, where it sustains the ATP production required for synaptic vesicle cycling. However, translocation occurs from presynaptic membranes other than synaptic vesicles and involves a distinct molecular mechanism.
Neurofilament light predicts neurological outcome after subarachnoid haemorrhage.
Brain : a journal of neurology, 2021

To improve outcome prediction following subarachnoid haemorrhage (SAH), we sought a biomarker integrating early brain injury and multiple secondary pathological processes in a prospective study of 42 non-traumatic SAH patients and 19 control individuals. Neurofilament light (NF-L) was elevated in CSF and serum following SAH. CSF and serum NF-L on Days 1-3 post-SAH strongly predicted modified Rankin score at 6 months, independent of World Federation of Neurosurgical Societies (WFNS) score. NF-L from Day 4 onwards also had a profound impact on outcome. To link NF-L to a SAH-specific pathological process, we investigated NF-L's relationship with extracellular haemoglobin. Most CSF haemoglobin was not complexed with haptoglobin, yet was able to be bound by exogenous haptoglobin i.e. haemoglobin was scavengeable. CSF scavengeable haemoglobin was strongly predictive of subsequent CSF NF-L. Next, we investigated NF-L efflux from the brain after SAH. Serum and CSF NF-L correlated positively. The serum/CSF NF-L ratio was lower in SAH versus control subjects, in keeping with glymphatic efflux dysfunction after SAH. CSF/serum albumin ratio was increased following SAH versus controls. The serum/CSF NF-L ratio correlated negatively with the CSF/serum albumin ratio, indicating that transfer of the two proteins across the blood-brain interface is dissociated. In summary, NF-L is a strong predictive marker for SAH clinical outcome, adding value to the WFNS score, and is a promising surrogate end point in clinical trials.
Assessing the impact of dementia inclusive environmental adjustment in the emergency department.
Dementia (London, England), 2021

Acute hospitals, in particular the emergency department, can be disorienting for people living with dementia. As part of a larger project to improve care for people living with dementia, dementia-inclusive modifications were made to two emergency department bays in a large acute care hospital in Ireland. Modifications to spatial configuration included noise reduction, altered lighting and the addition of an orientation aid and fixed seating for relatives.
Ex-vivo quantification of ovine pia arachnoid complex biomechanical properties under uniaxial tension.
Fluids and barriers of the CNS, 2020

The pia arachnoid complex (PAC) is a cerebrospinal fluid-filled tissue conglomerate that surrounds the brain and spinal cord. Pia mater adheres directly to the surface of the brain while the arachnoid mater adheres to the deep surface of the dura mater. Collagen fibers, known as subarachnoid trabeculae (SAT) fibers, and microvascular structure lie intermediately to the pia and arachnoid meninges. Due to its structural role, alterations to the biomechanical properties of the PAC may change surface stress loading in traumatic brain injury (TBI) caused by sub-concussive hits. The aim of this study was to quantify the mechanical and morphological properties of ovine PAC.
Estimation of drug receptor occupancy when non-displaceable binding differs between brain regions – extending the simplified reference tissue model.
British journal of clinical pharmacology, 2015

The simplified reference tissue model (SRTM) is used for estimation of receptor occupancy assuming that the non-displaceable binding in the reference region is identical to the brain regions of interest. The aim of this work was to extend the SRTM to also account for inter-regional differences in non-displaceable concentrations, and to investigate if this model allowed estimation of receptor occupancy using white matter as reference. It was also investigated if an apparent higher affinity in caudate compared with other brain regions, could be better explained by a difference in the extent of non-displaceable binding.
Vitamins A, C, and E May Reduce Intestinal 210Po Levels after Ingestion.
Health physics, 2016

Damage to the gut mucosa is a probable contributory cause of death from ingested Po. Therefore, medical products are needed that can prevent, mitigate, and/or repair gastrointestinal (GI) damage caused by high-LET radiation emitted by Po. The present studies investigated the capacity of a diet highly enriched with vitamins A, C, and E (vitamin ACE) to protect against intestinal mucosal damage indicated by functional reductions in nutrient transport caused by orally ingested Po. Mice were gavaged with 0 or 18.5 kBq Po-citrate and fed a control or vitamin ACE-enriched diet (the latter beginning either 96 h before or immediately after gavage). Mouse intestines significantly retained Po on day 8 post-gavage. The concentration of Po in intestinal tissues was significantly (p<0.05) lower in all vitamin ACE groups compared to control. There were borderline significant Po-induced reductions in intestinal absorption of D-fructose. The combination of vitamins A, C, and E may reduce Po incorporation in the intestines when given before, or enhance decorporation when provided after, Po gavage.
Transcriptome profiling reveals Th2 bias and identifies endogenous itch mediators in poison ivy contact dermatitis.
JCI insight, 2019

In the United States, poison ivy exposure is the most common naturally occurring allergen to cause allergic contact dermatitis (ACD). The immune and pruritic mechanisms associated with poison ivy ACD remain largely unexplored. Here, we compared skin whole transcriptomes and itch mediator levels in mouse ACD models induced by the poison ivy allergen, urushiol, and the synthetic allergen, oxazolone. The urushiol model produced a Th2-biased immune response and scratching behavior, resembling findings in poison ivy patients. Urushiol-challenged skin contained elevated levels of the cytokine thymic stromal lymphopoietin (TSLP), a T-cell regulator and itch mediator, and pruritogenic serotonin (5-HT) and endothelin (ET-1), but not substance P (SP) or histamine. The oxazolone model generated a mixed Th1/Th2 response associated with increased levels of substance P, 5-HT, ET-1, but not TSLP or histamine. Injections of a TSLP monoclonal neutralizing antibody, serotonergic or endothelin inhibitors, but not SP inhibitors or antihistamines, reduced scratching behaviors in urushiol-challenged mice. Our findings suggest that the mouse urushiol model may serve as a translational model of human poison ivy ACD study. Inhibiting signaling by TSLP and other cytokines may represent alternatives to the standard steroid/antihistamine regimen for steroid-resistant or -intolerant patients and in exaggerated systemic responses to poison ivy.
PGE1 and PGA1 bind to Nurr1 and activate its transcriptional function.
Nature chemical biology, 2020

The orphan nuclear receptor Nurr1 is critical for the development, maintenance and protection of midbrain dopaminergic (mDA) neurons. Here we show that prostaglandin E1 (PGE1) and its dehydrated metabolite, PGA1, directly interact with the ligand-binding domain (LBD) of Nurr1 and stimulate its transcriptional function. We also report the crystallographic structure of Nurr1-LBD bound to PGA1 at 2.05 Å resolution. PGA1 couples covalently to Nurr1-LBD by forming a Michael adduct with Cys566, and induces notable conformational changes, including a 21° shift of the activation function-2 helix (H12) away from the protein core. Furthermore, PGE1/PGA1 exhibit neuroprotective effects in a Nurr1-dependent manner, prominently enhance expression of Nurr1 target genes in mDA neurons and improve motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse models of Parkinson's disease. Based on these results, we propose that PGE1/PGA1 represent native ligands of Nurr1 and can exert neuroprotective effects on mDA neurons, via activation of Nurr1's transcriptional function.
Should I stay or should I go? How local-global implicit temporal expectancy shapes proactive motor control: An hdEEG study.
NeuroImage, 2020

In this study, we investigated the effect of global temporal prediction on the brain capability to implicitly adjust proactive motor control. We used the Dynamic Temporal Prediction (DTP), in which local and global predictions of an imperative stimulus were manipulated by using different stimulus-onset asynchronies (SOAs), presented with several distribution probabilities. At a behavioural level, the results show a performance adjustment (reaction time decrease) depending on the implicit use of global prediction. At a neurophysiological level, three separate computational steps underlying motor control were investigated. First, the expectancy implementation was associated with global probability-dependent contingent negative variation (CNV) modulation supported by the recruitment of a frontoparietal network involving the anterior cingulate, the left intraparietal sulcus, the occipital, and the premotor areas. Second, the response implementation was modulated by the global prediction fostering stimulus processing (P3 increase) at the motor response level, as suggested by both oscillatory (beta desynchronization), as well as source analysis (frontal cortical network). Third, the expectancy violation lead to a negativity increase (omission-detection potential) time locked to the global rule violation and additionally, to delta and theta power increase interpreted as inhibitory control and rule violation detection, respectively. The expectancy violation further engaged a left lateralized network including the temporal parietal junction (TPJ) and the motor cortex, suggesting involvement of attentional reorienting and a motor adjustment. Finally, these findings provide new insights on the neurocognitive mechanisms underlying proactive motor control, suggesting an overlapping between implicit and explicit processes.
Medical and neurobehavioural phenotypes in male and female carriers of Xp22.31 duplications in the UK Biobank.
Human molecular genetics, 2020

Deletions spanning the STS (steroid sulfatase) gene at Xp22.31 are associated with X-linked ichthyosis, corneal opacities, testicular maldescent, cardiac arrhythmia, and higher rates of developmental and mood disorders/traits, possibly related to the smaller volume of some basal ganglia structures. The consequences of duplication of the same genomic region have not been systematically assessed in large or adult samples, although evidence from case reports/series has indicated high rates of developmental phenotypes. We compared multiple measures of physical and mental health, cognition and neuroanatomy in male (n = 414) and female (n = 938) carriers of 0.8-2.5 Mb duplications spanning STS, and non-carrier male (n = 192, 826) and female (n = 227, 235) controls from the UK Biobank (recruited aged 40-69 from the UK general population). Clinical and self-reported diagnoses indicated a higher prevalence of inguinal hernia and mania/bipolar disorder respectively in male duplication carriers, and a higher prevalence of gastro-oesophageal reflux disease and blistering/desquamating skin disorder respectively in female duplication carriers; duplication carriers also exhibited reductions in several depression-related measures, and greater happiness. Cognitive function and academic achievement did not differ between comparison groups. Neuroanatomical analysis suggested greater lateral ventricle and putamen volume in duplication carriers. In conclusion, Xp22.31 duplications appear largely benign, but could slightly increase the likelihood of specific phenotypes (although results were only nominally-significant). In contrast to deletions, duplications might protect against depressive symptoms, possibly via higher STS expression/activity (resulting in elevated endogenous free steroid levels), and through contributing towards an enlarged putamen volume. These results should enable better genetic counselling of individuals with Xp22.31 microduplications.
Objective Patterns of Face Recognition Deficits in 165 Adults with Self-Reported Developmental Prosopagnosia.
Brain sciences, 2019

In the last 15 years, increasing numbers of individuals have self-referred to research laboratories in the belief that they experience severe everyday difficulties with face recognition. The condition "developmental prosopagnosia" (DP) is typically diagnosed when impairment is identified on at least two objective face-processing tests, usually involving assessments of face perception, unfamiliar face memory, and famous face recognition. While existing evidence suggests that some individuals may have a mnemonic form of prosopagnosia, it is also possible that other subtypes exist. The current study assessed 165 adults who believe they experience DP, and 38% of the sample were impaired on at least two of the tests outlined above. While statistical dissociations between face perception and face memory were only observed in four cases, a further 25% of the sample displayed dissociations between impaired famous face recognition and intact short-term unfamiliar face memory and face perception. We discuss whether this pattern of findings reflects (a) limitations within dominant diagnostic tests and protocols, (b) a less severe form of DP, or (c) a currently unrecognized but prevalent form of the condition that affects long-term face memory, familiar face recognition or semantic processing.
National outcomes and characteristics of patients admitted to Swedish intensive care units for COVID-19: A registry-based cohort study.
European journal of anaesthesiology, 2021

Mortality among patients admitted to intensive care units (ICUs) with COVID-19 is unclear due to variable follow-up periods. Few nationwide data are available to compare risk factors, treatment and outcomes of COVID-19 patients after ICU admission.
Therapeutic developments for autoimmune demyelinating diseases: Musings from an MD (mouse doctor).
Journal of neuroimmunology, 2017

This paper is a summary of the lecture given by Dr. Racke at a meeting celebrating the 40th anniversary of the Neuroimmunology Branch (NIB). This talk was the keynote address given at the end of the first day of lectures after a toast given by Cedric Raine, Dale McFarlin's "brother from another mother". Several speakers during the day gave their own musings on the reasons for the success of the NIB, and this lecture attempted to give a sense to those present of the speaker's view for the reason of this success.
Neuroscience, the microscope and the truth: personal philosophical considerations by a professor emeritus of neuropathology and neurology.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2016

The article starts from the conception that the world is introduced in our mind though linguistic categories and that between us and the world there is always the language. This implies that to denominate still means to know. The visual pathway is described from the retina to the occipital cortex with the related phenomena of the recognition of the external world, through the Gestalt psychology, the reciprocal influence of sign/receptor, the mental images or patterns, the cognition, the conscience and memory. As an example, the microscope is presented as a tool for exploring the external world. The scientific objectivity is given by the dialectic with the scientific inter-subjectivity that, if abandoned, may give origin to mistakes or dangerous ideologies. The scientific truth is not absolute and perennial, but contingent and temporary and it is validated by the epochal parameters. The features outlined may apply to scientific research, clinical reasoning and also to the general behavior.
Effect of pallidal deep-brain stimulation on articulation rate in dystonia.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2019

Pallidal deep-brain stimulation of the internal globus pallidus (GPi-DBS) is an effective treatment for dystonia. However, GPi-DBS may cause important stimulation-induced side effects such as hypokinetic dysarthria, which is particularly manifested by articulation rate abnormalities. However, little data regarding the effect of the location of the electrode and stimulation parameters for pallidal stimulation on articulation rate in dystonia is available. Speech data were acquired from 18 dystonic patients with GPi-DBS and 18 matched healthy controls. Each of dystonic patients was tested twice within 1 day in both the GPi-DBS ON and GPi-DBS OFF stimulation conditions. Compared to healthy controls, the decreased diadochokinetic rate and slower articulation rate in dystonic patients were observed in both stimulation conditions. No significant differences in speech rate measures between stimulation conditions were detected with no relation to contact localization and stimulation intensity. Our findings do not support the use articulation rate as a surrogate marker of stimulation-induced changes to the speech apparatus in dystonia.
Task Feedback Processing Differs Between Young and Older Adults in Visuomotor Rotation Learning Despite Similar Initial Adaptation and Savings.
Neuroscience, 2020

Ageing has been suggested to affect sensorimotor adaptation by impairing explicit strategy use. Here we recorded electrophysiological (EEG) responses during visuomotor rotation in both young (n = 24) and older adults (n = 25), to investigate the neural processes that underpin putative age-related effects on adaptation. We measured the feedback related negativity (FRN) and the P3 in response to task-feedback, as electrophysiological markers of task error processing and outcome evaluation. The two age groups adapted similarly and showed comparable after effects and savings when re-exposed to the same perturbation several days after the initial session. Older adults, however, had less distinct EEG responses (i.e., reduced FRN amplitudes) to negative and positive task feedback. The P3 did not differ between age groups. Both young and older adults also showed a sustained late positivity following task feedback. Measured at the frontal electrode Fz, this sustained activity was negatively associated with both the amount of voluntary disengagement of explicit strategy and savings. In conclusion, despite preserved task performance, we find clear differences in neural responses to errors in older people, which suggests that there is a fundamental decline in this aspect of sensorimotor brain function with age.
VTA Glutamate Neuron Activity Drives Positive Reinforcement Absent Dopamine Co-release.
Neuron, 2020

Like ventral tegmental area (VTA) dopamine (DA) neurons, VTA glutamate neuron activity can support positive reinforcement. However, a subset of VTA neurons co-release DA and glutamate, and DA release might be responsible for behavioral reinforcement induced by VTA glutamate neuron activity. To test this, we used optogenetics to stimulate VTA glutamate neurons in which tyrosine hydroxylase (TH), and thus DA biosynthesis, was conditionally ablated using either floxed Th mice or viral-based CRISPR/Cas9. Both approaches led to loss of TH expression in VTA glutamate neurons and loss of DA release from their distal terminals in nucleus accumbens (NAc). Despite loss of the DA signal, optogenetic activation of VTA glutamate cell bodies or axon terminals in NAc was sufficient to support reinforcement. These results suggest that glutamate release from VTA is sufficient to promote reinforcement independent of concomitant DA co-release, establishing a non-DA mechanism by which VTA activity can support reward-seeking behaviors.
Experiencing meditation - Evidence for differential effects of three contemplative mental practices in micro-phenomenological interviews.
Consciousness and cognition, 2018

Despite increasing interest in effects of meditation, systematic in-depth research on how it qualitatively feels to engage in different kinds of contemplative practices is still missing. To fill this gap, we explore the validity of Micro-phenomenological Interviews (MpI) to assess experiences during breathing meditation (BM), observing-thought meditation (OTM), and loving-kindness meditation (LKM). We performed psycholinguistic analyses, quantitative ratings and qualitative explorations of 104 MpI (N = 57). All results reveal differential affective, bodily and sensorial fingerprints: BM-transcripts contain the most body-related vocabulary, specifically sensations in nose and abdomen. OTM-transcripts contain the most cognition-related vocabulary. OTM is experienced in head and face. LKM-transcripts contain the most vocabulary related to socio-affective processes. LKM is associated to love, sensations around the heart, and warmth. The LKM-outcomes were replicated with another independent set of MpI. These findings verify the merit of MpI as a scientific tool to gain reliable first-person data beyond questionnaires or rating scales.
Retrograde and anterograde memory following selective damage to the dorsolateral entorhinal cortex.
Neurobiology of learning and memory, 2014

Anatomical and electrophysiological evidence suggest the dorsolateral entorhinal cortex (DLEC) is involved in processing spatial information, but there is currently no consensus on whether its functions are necessary for normal spatial learning and memory. The present study examined the effects of excitotoxic lesions of the DLEC on retrograde and anterograde memory on two tests of allocentric spatial learning: a hidden fixed-platform watermaze task, and a novelty-preference-based dry-maze test. Deficits were observed on both tests when training occurred prior to but not following n-methyl d-aspartate (NMDA) lesions of DLEC, suggesting retrograde memory impairment in the absence of anterograde impairments for the same information. The retrograde memory impairments were temporally-graded; rats that received DLEC lesions 1-3 days following training displayed deficits, while those that received lesions 7-10 days following training performed like a control group that received sham surgery. The deficits were not attenuated by co-infusion of tetrodotoxin, suggesting they are not due to disruption of neural processing in structures efferent to the DLEC, such as the hippocampus. The present findings provide evidence that the DLEC is involved in the consolidation of allocentric spatial information.