A5061265452- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Response and Inflammation
- Immune cells in cancer
- Neurological Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- MicroRNA in disease regulation
- Spinal Cord Injury Research
- Acute Ischemic Stroke Management
- Atherosclerosis and Cardiovascular Diseases
- S100 Proteins and Annexins
- Memory and Neural Mechanisms
- Extracellular vesicles in disease
- Circular RNAs in diseases
- Neurogenesis and neuroplasticity mechanisms
- Inflammation biomarkers and pathways
- Calpain Protease Function and Regulation
- Spinal Dysraphism and Malformations
- Barrier Structure and Function Studies
- Signaling Pathways in Disease
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Olfactory and Sensory Function Studies
- Neuroscience of respiration and sleep
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- GABA and Rice Research
University of Southern Denmark
2015-2024
Odense University Hospital
2020-2024
Dynamic Imaging (United Kingdom)
2023
University Medical Center Hamburg-Eppendorf
2021
Universität Hamburg
2021
Lundbeck (Denmark)
2013-2020
Institute of Molecular Medicine
2016
Roche (Switzerland)
2016
Ontario Institute for Cancer Research
2011
Princess Margaret Cancer Centre
2011
Recently, thousands of circular RNAs (circRNAs) have been discovered in various tissues and cell types from human, mouse, fruit fly nematodes. However, expression circRNAs across mammalian brain development has never examined. Here we profile the circRNA five at up to six time-points during fetal porcine development, constituting first report a large animal. An unbiased analysis reveals highly complex regulation pattern RNAs, with distinct spatio-temporal profile. The amount complexity was...
Microglia and infiltrating leukocytes are considered major producers of tumor necrosis factor (TNF), which is a crucial player in cerebral ischemia brain inflammation. We have identified neuroprotective role for microglial-derived TNF mice. show that cortical infarction behavioral deficit significantly exacerbated TNF-knock-out (KO) mice compared with wild-type By using situ hybridization, immunohistochemistry, green fluorescent protein bone marrow (BM)-chimeric mice, was shown to be...
Abstract Background Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are expressed by microglia infiltrating macrophages following ischemic stroke. Whereas IL-1β is primarily neurotoxic in stroke, TNF-α may have and/or neuroprotective effects. We investigated whether synthesized overlapping or segregated populations of cells after stroke mice. Methods used flow cytometry immunohistochemistry to examine cellular co-expression at 6, 12 24 hours permanent middle cerebral artery...
Inhibition of the ternary protein complex synaptic scaffolding postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and N -methyl- d -aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are lacking. Here we report design synthesis novel dimeric inhibitor, Tat- PEG4(IETDV) 2 (Tat- -dimer), which binds tandem PDZ1-2 domain PSD-95 with an unprecedented high affinity 4.6 nM, displays extensive...
Activated microglia play an essential role in inflammatory responses elicited the central nervous system (CNS). Microglia-derived extracellular vesicles (EVs) are suggested to be involved propagation of signals and modulation cell-to-cell communication. However, there is a lack knowledge on regulation EVs how this turn facilitates communication between cells brain. Here, we characterized microglial under conditions investigated effects inflammation EV size, quantity, protein content.We have...
Abstract Preclinical and clinical proof-of-concept studies have suggested the effectiveness of pharmacological modulation inflammatory cytokines in ischemic stroke. Experimental evidence shows that targeting tumor necrosis factor (TNF) interleukin (IL)-1 holds promise, these are considered prime targets development new stroke therapies. So far, however, information on cellular expression TNF IL-1 human brain is sparse. We studied 14 cases post-mortem stroke, representing 21 specimens...
The innate immune system contributes to the outcome after stroke, where neuroinflammation and post-stroke systemic depression are central features. Tumor necrosis factor (TNF), which exists in both a transmembrane (tm) soluble (sol) form, is known sustain complex inflammatory responses associated with stroke. We tested effect of systemically blocking only solTNF versus tmTNF on infarct volume, functional inflammation focal cerebral ischemia. used XPro1595 (a dominant-negative inhibitor...
Abstract Migraine is a complex brain disorder, and understanding the complexity of this prevalent disease could improve quality life for millions people. Familial Hemiplegic type 2 (FHM2) subtype migraine with aura co-morbidities like epilepsy/seizures, cognitive impairments psychiatric manifestations, such as obsessive-compulsive disorder (OCD). FHM2 disease-mutations locate to ATP1A2 gene encoding astrocyte-located α -isoform sodium-potassium pump (α Na + /K -ATPase). We show that knock-in...
Abstract Focal cerebral ischaemia has an initial phase of inflammation and tissue injury followed by a later resolution repair. Mass spectrometry imaging (desorption electrospray ionization matrix assisted laser desorption ionization) was applied on brain sections from mice 2 h, 24 5d, 7d, 20d after permanent focal ischaemia. Within N -acyl-phosphatidylethanolamines, lysophosphatidylcholine, ceramide accumulated, while sphingomyelin disappeared. At the stages, bis(monoacylglycero)phosphate...
Background: Ischemic stroke causes increased blood-brain barrier permeability and release of markers axonal damage inflammation. To investigate diagnostic prognostic roles neurofilament light chain (NF-L), we assessed levels NF-L, S100B, interleukin-6 (IL-6), E-selectin, vascular endothelial growth factor-A (VEGF-A), cell adhesion molecule-1 (VCAM-1), intercellular (ICAM-1) in patients with acute ischemic or transient attack (TIA) healthy controls. Methods: We studied (NF) expression 2 cases...
Abstract The N ‐acylethanolamines (NAEs) and 2‐arachidonoylglycerol (2‐AG) are bioactive lipids that can modulate inflammatory responses protect neurons against glutamatergic excitotoxicity. We have used a model of focal cerebral ischemia in young adult mice to investigate the relationship between endogenous NAEs. Over first 24 h after induction permanent middle artery occlusion, we observed time‐dependent increase all investigated NAEs, except for anandamide. Moreover, found an accumulation...
Brain injury caused by ischemia is a major cause of human mortality and physical/cognitive disability worldwide. Experimentally, brain can be induced surgically permanent middle cerebral artery occlusion. Using this model, we studied the influence transthyretin in ischemic stroke. Transthyretin (TTR) normally responsible for transport thyroid hormones retinol blood CSF. We found that TTR null mice (TTR(-/-) ) did not show significant differences cortical infarction 24 h after occlusion...
Microglia respond to focal cerebral ischemia by increasing their production of the neuromodulatory cytokine tumor necrosis factor, which exists both as membrane-anchored factor and cleaved soluble forms. We previously demonstrated that knockout mice display increased lesion volume after ischemia, suggesting is neuroprotective in experimental stroke. Here, we extend our studies show with intact but no reduced infarct volumes at one five days This was associated improved functional outcome No...
Lymphocytes have dichotomous functions in ischemic stroke. Regulatory T cells are protective, while IL-17A from innate lymphocytes promotes the infarct growth. With recent advances of cell-subtype specific transgenic mouse models it now has become possible to study complex interplay cell subpopulations stroke.In a murine model experimental stroke we analyzed effects IL-10 on functional outcome for up 14 days post-ischemia and defined source brains based immunohistochemistry, flow cytometry,...
Cerebral ischemic stroke is a leading cause of morbidity and mortality globally. However, the mechanisms underlying injury remain poorly understood. Here, it found that deficiency ubiquitin-specific protease USP25 significantly aggravate in mice. has no impact on neuronal death under hypoxic conditions, but reduced stroke-induced loss neurological deficits by inhibiting microglia-mediated neuroinflammation. Mechanistically, restricts activation NF-κB MAPK signaling regulating TAB2. As...
The pro-inflammatory cytokine interferon-gamma (IFNgamma) has traditionally been associated with inflammatory CNS disease and more recently ischemia-induced pathology. Using a murine model of focal cerebral ischemia, we found no evidence for induction IFNgamma mRNA after permanent middle artery occlusion. In addition, that mice deficient in or receptors developed neocortical infarcts similar size to those wild type. contrast, MBP promoter-IFNgamma-transgenic consistently significantly larger...
Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death and promotes functional recovery after stroke. However, core actions endogenous IFN-β signaling stroke are unclear. To address this question, we used two clinically relevant models focal cerebral ischemia,...