Publications by authors named "Stefan P Koch"

Introduction: Magnetic Resonance Elastography (MRE) allows the non-invasive quantification of tumor biomechanical properties . With increasing incidence of brain metastases, there is a notable absence of appropriate preclinical models to investigate their biomechanical characteristics. Therefore, the purpose of this work was to assess the biomechanical characteristics of B16 melanoma brain metastases (MBM) and compare it to murine GL261 glioblastoma (GBM) model using multifrequency MRE with tomoelastography post processing.

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  • Anti-contactin associated protein receptor 2 (CASPR2) encephalitis is a serious autoimmune condition with a wide range of symptoms, including behavioral issues, cognitive decline, seizures, and neuropathic pain.
  • Researchers isolated and analyzed autoantibodies from the cerebrospinal fluid of patients, successfully cloning four monoclonal antibodies that targeted CASPR2 and demonstrated high binding affinity to brain and nerve tissues.
  • Experiments in animal models showed that these antibodies could disrupt CASPR2's normal function and lead to brain hyperexcitability, emphasizing their role in the disease and highlighting new techniques for studying related neuropsychiatric symptoms.
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Multiple sclerosis (MS) is a chronic neuroinflammatory disease that involves both white and gray matter. Although gray matter damage is a major contributor to disability in MS patients, conventional clinical magnetic resonance imaging (MRI) fails to accurately detect gray matter pathology and establish a clear correlation with clinical symptoms. Using magnetic resonance elastography (MRE), we previously reported global brain softening in MS and experimental autoimmune encephalomyelitis (EAE).

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  • Late-onset Alzheimer's disease (LOAD) significantly impacts seniors, causing issues like memory loss and confusion, with Apolipoprotein-E (ApoE) recognized as a key risk factor for the condition.
  • The study hypothesizes that ApoE’s effects on LOAD risk might originate from changes in brain network architecture during neurodevelopment.
  • Using diffusion tensor imaging (DTI) and graph theory, researchers found that ApoE knockout mice exhibited distinct differences in brain connectivity compared to wild-type mice, suggesting ApoE plays a crucial role in how brain networks develop, which could influence vulnerability to LOAD.
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Decreased hippocampal connectivity and disruption of functional networks are established resting-state functional MRI (rs-fMRI) features that are associated with neuropsychiatric symptom severity in human anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. However, the underlying pathophysiology of NMDAR encephalitis remains poorly understood. Application of patient-derived monoclonal antibodies against the NR1 (GluN1) subunit of the NMDAR now allows for the translational investigation of functional connectivity in experimental murine NMDAR antibody disease models with neurodevelopmental disorders.

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Background: Prediction of poststroke outcome using the degree of subacute deficit or magnetic resonance imaging is well studied in humans. While mice are the most commonly used animals in preclinical stroke research, systematic analysis of outcome predictors is lacking.

Methods: We intended to incorporate heterogeneity into our retrospective study to broaden the applicability of our findings and prediction tools.

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The generation of appropriate behavioral responses involves dedicated neuronal circuits. The cortico-striatal-thalamo-cortical loop is especially important for the expression of motor routines and habits. Defects in this circuitry are closely linked to obsessive stereotypic behaviors, hallmarks of neuropsychiatric diseases including autism spectrum disorders (ASDs) and obsessive-compulsive disorders (OCDs).

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  • Magnetic resonance imaging (MRI) is essential for detecting ischemic stroke lesions in mice, but manual segmentation is difficult and inconsistent.
  • A new automated segmentation method using deep learning simplifies this process by working directly with raw MRI scans, minimizing preprocessing steps.
  • Results show that the automated method achieves higher accuracy in lesion segmentation compared to manual methods, reducing individual bias and standardizing results across research studies.
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Patients with multiple sclerosis consistently show widespread changes in functional connectivity. Yet, alterations are heterogeneous across studies, underscoring the complexity of functional reorganization in multiple sclerosis. Here, we aim to provide new insights by applying a time-resolved graph-analytical framework to identify a clinically relevant pattern of dynamic functional connectivity reconfigurations in multiple sclerosis.

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Paracrine cerebral Interleukin 6 (Il6) is relevant for stroke recovery, but systemic Il6 elevation may worsen outcome. Hence, paracrine Il6 response modulation within the neurovascular unit has emerged as an attractive therapeutic approach. Lithium modulates Il6 responses and improves stroke outcome.

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Aims: Glioblastomas are high-grade brain tumours that are characterised by the accumulation of brain-resident microglia and peripheral macrophages. Recruitment of these myeloid cells can be facilitated by CCR2/CCL2 signalling. Besides the well-known CCR2 macrophages, we have identified microglia expressing CCR2 in glioma tissues.

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The hippocampus is a very heterogeneous brain structure with different mechanical properties reflecting its functional variety. In particular, adult neurogenesis in rodent hippocampus has been associated with specific viscoelastic properties in vivo and ex vivo. Here, we study the microscopic mechanical properties of hippocampal subregions using ex vivo atomic force microscopy (AFM) in correlation with the expression of GFP in presence of the nestin promoter, providing a marker of neurogenic activity.

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Aims: Carotid artery disease is frequent and can result in chronic modest hypoperfusion of the brain. If no transient ischemic attack or stroke occur, it is classified asymptomatic. In the long-term, though, it can lead to cognitive impairment.

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Background: Connectome analysis of neuroimaging data is a rapidly expanding field that offers the potential to diagnose, characterize, and predict neurological disease. Animal models provide insight into biological mechanisms that underpin disease, but connectivity approaches are currently lagging in the rodent.

Methods: We present a pipeline adapted for structural and functional connectivity analysis of the mouse brain, and we tested it in a mouse model of vascular dementia.

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Subsurface blood vessels in the cerebral cortex have been identified as a bottleneck in cerebral perfusion with the potential for collateral remodeling. However, valid techniques for non-invasive, longitudinal characterization of neocortical microvessels are still lacking. In this study, we validated contrast-enhanced magnetic resonance imaging (CE-MRI) for characterization of vascular changes in a model of spontaneous collateral outgrowth following chronic cerebral hypoperfusion.

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Neuroinflammatory processes occurring during multiple sclerosis cause disseminated softening of brain tissue, as quantified by magnetic resonance elastography (MRE). However, inflammation-mediated tissue alterations underlying the mechanical integrity of the brain remain unclear. We previously showed that blood-brain barrier (BBB) disruption visualized by MRI using gadolinium-based contrast agent (GBCA) does not correlate with tissue softening in active experimental autoimmune encephalomyelitis (EAE).

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Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by a late clinical onset of psychiatric, cognitive, and motor symptoms. Transcriptional dysregulation is an early and central disease mechanism which is accompanied by epigenetic alterations in HD. Previous studies demonstrated that targeting transcriptional changes by inhibition of histone deacetylases (HDACs), especially the class I HDACs, provides therapeutic effects.

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  • Placental hypoperfusion and hypoxia are major factors leading to fetal complications like growth restriction and preeclampsia, making it essential to develop biomarkers to study these issues in mice.
  • This study aimed to noninvasively measure placental oxygen levels using fluorine magnetic resonance imaging (F MRI) in a specific mouse model (Lgals1 deficient) associated with preeclampsia, with the expectation that oxygen levels would be lower in these knockout mice.
  • Results indicated that while oxygen levels did increase with higher oxygen content in the air, the decrease in oxygenation observed in knockout mice was only significant at the lowest oxygen level (30%) and reinforced that F MRI can effectively assess placental oxygenation in these
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Seasonal cycles govern life on earth, from setting the time for the mating season to influencing migrations and governing physiological conditions like hibernation. The effect of such changing conditions on behavior is well-appreciated, but their impact on the brain remains virtually unknown. We investigate long-term seasonal changes in the mammalian brain, known as Dehnel's effect, where animals exhibit plasticity in body and brain sizes to counter metabolic demands in winter.

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  • A study assessed the variability in lesion sizes during ischemic stroke experiments using the fMCAo model in C57BL/6 mice, linked to the patency of the posterior communicating artery (PcomA).
  • Measurement of PcomA size 24 hours after stroke was found to correlate negatively with lesion size, explaining 30% of the variability in stroked mice.
  • Implementing this measurement can increase the accuracy in evaluating treatment effects in stroke research by enhancing statistical power.
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Fetal growth restriction (FGR) is the most common pregnancy complication in developed countries. Pregnancies affected by FGR, frequently concur with complications and high risk of neonatal morbidity and mortality. To date, no approved treatment is available for pregnant women affected with FGR.

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Appetitive Pavlovian conditioning is a learning mechanism of fundamental biological and pathophysiological significance. Nonetheless, its exploration in humans remains sparse, which is partly attributed to the lack of an established psychophysiological parameter that aptly represents conditioned responding. This study evaluated pupil diameter and other ocular response measures (gaze dwelling time, blink duration and count) as indices of conditioning.

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Learning accounts of addiction and obesity emphasize the persistent power of Pavlovian reward cues to trigger craving and increase relapse risk. While extinction can reduce conditioned responding, Pavlovian relapse phenomena-the return of conditioned responding following successful extinction-challenge the long-term success of extinction-based treatments. Translational laboratory models of Pavlovian relapse could therefore represent a valuable tool to investigate the mechanisms mediating relapse, although so far human research has mostly focused on return of fear phenomena.

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Neuroinflammation can be monitored using fluorine-19 (F)-containing nanoparticles and F MRI. Previously we studied neuroinflammation in experimental autoimmune encephalomyelitis (EAE) using room temperature (RT) F radiofrequency (RF) coils and low spatial resolution F MRI to overcome constraints in signal-to-noise ratio (SNR). This yielded an approximate localization of inflammatory lesions.

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