A5070573910- Neonatal Respiratory Health Research
- Preterm Birth and Chorioamnionitis
- Infant Nutrition and Health
- Neonatal and fetal brain pathology
- Immune Response and Inflammation
- Reproductive System and Pregnancy
- Congenital Diaphragmatic Hernia Studies
- Neonatal and Maternal Infections
- Neuroscience of respiration and sleep
- Acute Kidney Injury Research
- Mesenchymal stem cell research
- Pediatric Hepatobiliary Diseases and Treatments
- Pregnancy and preeclampsia studies
- Complement system in diseases
- Inflammasome and immune disorders
- Cell death mechanisms and regulation
- Cardiac Ischemia and Reperfusion
- Phagocytosis and Immune Regulation
- Congenital Anomalies and Fetal Surgery
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Respiratory Support and Mechanisms
- Clinical Nutrition and Gastroenterology
- Traumatic Brain Injury and Neurovascular Disturbances
- Anesthesia and Neurotoxicity Research
- Congenital gastrointestinal and neural anomalies
Maastricht University
2016-2025
Maastricht University Medical Centre
2004-2020
University Medical Center
2013-2020
Perinatal Institute
2017
Pediatrics and Genetics
2017
Cincinnati Children's Hospital Medical Center
2011-2014
University of Cincinnati
2014
RELX Group (Netherlands)
2013
Universitair Ziekenhuis Brussel
2005
Vlaams Instituut voor Biotechnologie
2000
Ischemia followed by reperfusion leads to severe organ injury and dysfunction. Inflammation is considered be the most important cause of tissue in organs subjected ischemia. The mechanism that triggers inflammation after ischemia remains elucidated, although different causes have been postulated. We investigated role apoptosis induction damage renal Using a murine model, we demonstrate relationship between subsequent inflammation. At time reperfusion, administration antiapoptotic agents...
Abstract The reported requirement of functional Toll-like receptor (TLR)4 for resistance to Gram-negative pyelonephritis prompted us localize the expression TLR2 and TLR4 mRNA in kidney at cellular level by situ hybridization. majority constitutive was found be strategically located renal epithelial cells. Assuming that TLR is representative apical protein expression, this suggests these cells are able detect react with bacteria present lumen tubules. To gain insight regulation during...
Abstract Preterm neonates are susceptible to perinatal hypoxic-ischemic brain injury, for which no treatment is available. In a preclinical animal model of injury in ovine fetuses, we have demonstrated the neuroprotective potential systemically administered mesenchymal stromal cells (MSCs). The mechanism MSC unclear but suggested be paracrine, through secretion extracellular vesicles (EVs). Therefore, investigated this study protective effects cell-derived (MSC-EVs) preterm injury. Ovine...
Abstract The complement system has been shown to mediate renal ischemia-reperfusion (I/R) injury. However, the contribution of factor C5a I/R injury, in particular kidney, remains be established. In this study, we investigated impact blocking C5aR pathway on inflammatory response and function a murine model First, analyzed expression kidneys healthy mice. Intriguingly, found mesangial, as well tubular epithelial, cells. After was up-regulated epithelial addition, mRNA levels CXC chemokines...
Ischemia followed by reperfusion (I/R) causes apoptosis, inflammation, and tissue damage leading to organ malfunction. Ischemic preconditioning can protect against such injury. This study investigates the contribution of acute phase proteins alpha(1)-acid glycoprotein (AGP) alpha(1)-antitrypsin (AAT) protective effect ischemic in kidney.Exogenous AGP AAT inhibited apoptosis inflammation after 45 minutes renal I/R a murine model. administered at prevented 2 hours 24 hours, as evaluated...
Background. Complement has been implicated in the pathophysiology of renal ischemia-reperfusion (I/R) injury. However, mechanism underlying complement-mediated I/R injury is thus far unknown. To investigate involvement complement injury, we studied activation and deposition a murine model Furthermore, examined effect inhibition complement-factor C5 on Methods. Mice were subjected to 45 min unilateral ischemia subsequent contralateral nephrectomy reperfusion for 2, 12, or 24 hr. control...
Autoimmune diseases such as glomerulonephritis are exacerbated by infection. This study examined the effect of Toll-like receptor 4 (TLR4) ligand lipid A on development heterologous nephrotoxic nephritis. Administration antibody resulted in significant glomerular neutrophil infiltration and albuminuria only when a TLR4 was administered simultaneously. The contribution renal cells circulating leukocytes assessed. Bone marrow chimeras were constructed with or bone marrow-derived cells....
Chorioamnionitis is the most significant source of prenatal inflammation and preterm delivery. Prematurity are associated with compromised postnatal developmental outcomes, intestinal immune defence, gut barrier function vascular system. We developed a sheep model to study how antenatal development was affected by gestation and/or endotoxin induced chorioamnionitis.Chorioamnionitis at different gestational ages (GA). Animals were sacrificed low GA after 2d or 14d exposure chorioamnionitis....
Abstract Background Hypoxic-ischemic encephalopathy (HIE) is one of the most important causes brain injury in preterm infants. Preterm HIE predominantly caused by global hypoxia-ischemia (HI). In contrast, focal ischemia common adult and known to result cerebral inflammation activation peripheral immune system. These inflammatory responses are considered play an role adverse outcomes following ischemia. this study, we hypothesize that also involved after HI. Methods instrumented fetal sheep...
Hypoxic-ischemic encephalopathy (HIE) in preterm infants is a severe disease for which no curative treatment available. Cerebral inflammation and invasion of activated peripheral immune cells have been shown to play pivotal role the etiology white matter injury, clinical hallmark HIE infants. The objective this study was assess neuroprotective anti-inflammatory effects intravenously delivered mesenchymal stem (MSC) an ovine model HIE. In translational animal model, global hypoxia-ischemia...
Antenatal infection (i.e., chorioamnionitis) is an important risk factor for adverse neurodevelopmental outcomes after preterm birth. Destructive and developmental disturbances of the white matter are hallmarks brain injury. Understanding temporal effects antenatal in relation to onset neurological injury crucial development neurotherapeutics infants. However, these dynamics remain unstudied. Time-mated ewes were intra-amniotically injected with lipopolysaccharide at 5, 12, or 24 h 2, 4, 8,...
Blood-brain barrier (BBB) disruption is associated with hypoxia-ischemia (HI) induced brain injury and life-long neurological pathologies. Treatment options are limited. Recently, we found that mesenchymal stem/stromal cell derived extracellular vesicles (MSC-EVs) protected the in ovine fetuses exposed to HI. We hypothesized Annexin A1 (ANXA1), present MSC-EVs, contributed their therapeutic potential by targeting ANXA1/Formyl peptide receptor (FPR), thereby preventing loss of BBB integrity....
Vascular endothelial growth factor (VEGF) plays a vital role in promoting attachment and proliferation of cells, induces angiogenesis. In recent years, much research has been conducted on functionalization tissue engineering scaffolds with VEGF or VEGF-mimetic peptide to promote However, most chemical reactions are nonspecific require organic solvents, which can compromise control over alter peptide/protein activity. An attractive alternative is the fabrication functionalizable electrospun...
Warm ischemia-reperfusion (I/R) injury plays an important role in posttransplant organ failure. In particular, organs from marginal donors suffer I/R injury. Although iron has been implicated the pathophysiology of renal injury, mechanism iron-mediated remains to be established. The authors therefore investigated circulating redox-active experimental model for injury.Male Swiss mice were subjected unilateral ischemia 45 min, followed by contralateral nephrectomy and reperfusion. To...
Intra-amniotic exposure to proinflammatory agonists causes chorioamnionitis and fetal gut inflammation. Fetal inflammation is associated with mucosal injury impaired development. We tested whether this detrimental inflammatory response of the results from a direct local (gut derived) or an indirect mediated by chorioamnion/skin lung, since these organs are also in contact amniotic fluid. The gastrointestinal tract was isolated respiratory amnion/skin epithelia surgery time-mated ewes....
Abstract Co-existing infection/inflammation and birth asphyxia potentiate the risk of developing neonatal encephalopathy (NE) adverse outcome. In a newborn piglet model we assessed effect E. coli lipopolysaccharide (LPS) infusion started 4 h prior to continued for 48 after hypoxia on brain cell death systemic haematological changes compared LPS alone. sensitized resulted in an increase mortality (TUNEL positive cells) throughout whole brain, internal capsule, periventricular white matter...
Abstract Tissue injury as a consequence of ischemia followed by reperfusion is characterized early well late signs inflammation. The latter, among others, involves IFN-γ-dependent up-regulation MHC class I and II Ag expression. Employing murine model renal ischemia, we show that IL-18 mRNA coincides with caspase-1 activation at day 1 following ischemia. IFN-γ IL-12 are subsequently up-regulated 6 Combined, but not separate, in vivo neutralization the inducing cytokines reduces to similar...
Microbiota in the intestinal lumen provide an abundant source of potentially detrimental antigens, including lipopolysaccharide (LPS), a potent immunostimulatory product Gram-negative bacteria recognized by host via TLR-4 and MD-2. An aberrant immune response to LPS or other bacterial antigens has been linked inflammatory bowel disease (IBD) necrotizing enterocolitis (NEC).We investigated which cells express MD-2 normal inflamed ileum from neonates adults immunohistochemistry. Moreover, TLR4...