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Cindy Casteels

Possible papers associated with this exact author name in Arrow. This page groups case-insensitive exact name matches and is not a full identity disambiguation profile.

4 papers

1 author row

YNICL Journal 2020 Journal Article

Non-invasive characterization of amyotrophic lateral sclerosis in a hTDP-43A315T mouse model: A PET-MR study

Akila Weerasekera
Melissa Crabbé
Sandra O. Tomé
Willy Gsell
Diana Sima
Cindy Casteels
Tom Dresselaers
Christophe Deroose

Currently TAR DNA binding protein 43 (TDP-43) pathology, underlying Amyotrophic Lateral Sclerosis (ALS), remains poorly understood which hinders both clinical diagnosis and drug discovery efforts. To better comprehend the disease pathophysiology, positron emission tomography (PET) and multi-parametric magnetic resonance imaging (mp-MRI) provide a non-invasive mode to investigate molecular, structural, and neurochemical abnormalities in vivo. For the first time, we report the findings of a longitudinal PET-MR study in the TDP-43A315T ALS mouse model, investigating disease-related changes in the mouse brain. 2-deoxy-2-[18F]fluoro-D-glucose [18F]FDG PET showed significantly lowered glucose metabolism in the motor and somatosensory cortices of TDP-43A315T mice whereas metabolism was elevated in the region covering the bilateral substantia nigra, reticular and amygdaloid nucleus between 3 and 7 months of age, as compared to non-transgenic controls. MR spectroscopy data showed significant changes in glutamate + glutamine (Glx) and choline levels in the motor cortex and hindbrain of TDP-43A315T mice compared to controls. Cerebral blood flow (CBF) measurements, using an arterial spin labelling approach, showed no significant age- or group-dependent changes in brain perfusion. Diffusion MRI indices demonstrated transient changes in different motor areas of the brain in TDP-43A315T mice around 14 months of age. Cytoplasmic TDP-43 proteinaceous inclusions were observed in the brains of symptomatic, 18-month-old mice, but not in non-symptomatic transgenic or wild-type mice. Our results reveal that disease- and age-related functional and neurochemical alterations, together with limited structural changes, occur in specific brain regions of transgenic TDP-43A315T mice, as compared to their healthy counterparts. Altogether these findings shed new light on TDP-43A315T disease pathogenesis and may prove useful for clinical management of ALS.

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YNICL Journal 2016 Journal Article

The effective connectivity of the seizure onset zone and ictal perfusion changes in amygdala kindled rhesus monkeys

Evy Cleeren
Elsie Premereur
Cindy Casteels
Karolien Goffin
Peter Janssen
Wim Van Paesschen

Epileptic seizures are network-level phenomena. Hence, epilepsy may be regarded as a circuit-level disorder that cannot be understood outside this context. Better insight into the effective connectivity of the seizure onset zone and the manner in which seizure activity spreads could lead to specifically-tailored therapies for epilepsy. We applied the electrical amygdala kindling model in two rhesus monkeys until these animals displayed consistent stage IV seizures. At this stage, we investigated the effective connectivity of the amygdala by means of electrical microstimulation during fMRI (EM-fMRI). In addition, we imaged changes in perfusion during a seizure using ictal SPECT perfusion imaging. The spatial overlap between the connectivity network and the ictal perfusion network was assessed both at the regional level, by calculating Dice coefficients using anatomically defined regions of interest, and at the voxel level. The kindled amygdala was extensively connected to bilateral cortical and subcortical structures, which in many cases were connected multisynaptically to the amygdala. At the regional level, the spatial extents of many of these fMRI activations and deactivations corresponded to the respective increases and decreases in perfusion imaged during a stage IV seizure. At the voxel level, however, some regions showed residual seizure-specific activity (not overlapping with the EM-fMRI activations) or fMRI-specific activation (not overlapping with the ictal SPECT activations), indicating that frequently, only a part of a region anatomically connected to the seizure onset zone participated in seizure propagation. Thus, EM-fMRI in the amygdala of electrically-kindled monkeys reveals widespread areas that are often connected multisynaptically to the seizure focus. Seizure activity appears to spread, to a large extent, via these connected areas.

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YNIMG Journal 2008 Journal Article

Gender-dependent increases with healthy aging of the human cerebral cannabinoid-type 1 receptor binding using [18F]MK-9470 PET

Koen Van Laere
Karolien Goffin
Cindy Casteels
Patrick Dupont
Luc Mortelmans
Jan de Hoon
Guy Bormans

The endocannabinoid system (ECS) is implicated as a regulator of homeostasis of several cerebral functions and is a novel target for drug treatment of neuropyschiatric disorders. So far, the cerebral cannabinoid-type 1 receptor (CB1R) has only been studied using in vitro, animal model, electrophysiological and post-mortem data. We have used positron emission tomography (PET) using a high-affinity, subtype-selective radioligand, [18F]MK-9470, to assess the in vivo cerebral CB1R distribution and its variation with healthy aging and gender. Fifty healthy volunteers (25 M/25 F, 18–69 years) underwent [18F]MK-9470 PET. Parametric [18F]MK-9470 binding maps were constructed, corrected for partial volume effects and analyzed using statistical parametric mapping in a combined categorical (gender) and covariate (age) design. We found that [18F]MK-9470 binding to CB1R increased with aging but only in women (p FWE<0. 05, corrected for multiple comparisons); this was most pronounced in the basal ganglia, lateral temporal cortex and limbic system, especially in the hippocampus. Men showed higher [18F]MK-9470 binding then women (p <0. 001, uncorrected), in clusters of the limbic system and cortico-striato-thalamic-cortical circuit. Region-dependent and gender-related upregulation of [18F]MK-9470 binding with aging is in line with ex vivo findings in rodent studies and may be associated with a changing homeostatic capacity or compensation mechanisms in the ECS that is modulated by sex hormones. In vivo PET of the CB1R will likely improve our understanding of the ECS in several neurological and psychiatric disorders.

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YNIMG Journal 2007 Journal Article

Motor- and food-related metabolic cerebral changes in the activity-based rat model for anorexia nervosa: A voxel-based microPET study

Kris van Kuyck
Cindy Casteels
Peter Vermaelen
Guy Bormans
Bart Nuttin
Koen Van Laere

Anorexia nervosa (AN) is a disorder that is difficult to treat with psycho- or pharmacotherapy. In order to identify involved neurocircuitry, we investigated the cerebral metabolic alterations in the activity-based anorexia (ABA) rat model, where restriction of the food intake period induces hyperactivity and decreased body weight. Cerebral 18F-fluorodeoxyglucose uptake was investigated in rats in the activity-based anorexia model (n =9) and compared to controls (n =10), using a CTI Focus microPET 220. Regional metabolic changes were investigated using statistical parametric mapping (SPM2) and correlated to weight and hyperactivity measures on a voxel-by-voxel basis. Higher regional metabolism was found in ABA rats in the mediodorsal thalamus, ventral pontine nuclei and cerebellum, while hypometabolism was seen in the left rhinal and bilateral insular cortex, and bilateral ventral striatum (p <0. 001). A positive correlation was observed between body weight loss and brain metabolism in the cingulate cortex and surrounding motor and somatosensory cortex (p <0. 001). Thus, in the ABA model metabolic changes are present in brain areas related to disease status and weight loss, which share several characteristics with the human disease.

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