Johan S H Vles

Maastricht University, Maestricht, Limburg, Netherlands

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Publications (166)461.28 Total impact

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    ABSTRACT: Diagnostic overshadowing refers to the underdiagnosis of comorbid conditions in children with known neurological diagnoses. To demonstrate diagnostic overshadowing we determined the prevalence of attention deficit-hyperactivity disorders (ADHD) in a cohort of children with a wide range of neurological disabilities. The study cohort consisted of 685 children (mean age 10.3 years, SD: 3.1; 425 boys and 260 girls) who visited a tertiary outpatient multidisciplinary clinic for neurological learning disabilities. Patients with ADHD were identified by retrospective chart review using DSM-IV criteria. The prevalence of ADHD in this cohort was 38.8% (266 children); of these children only 28.2% (75 children) were diagnosed with ADHD before referral. ADHD is a common problem in children with neurological disabilities and may be underdiagnosed due to overshadowing of somatic, physical or syndromal features of the disability. In our heterogeneous population ADHD was overshadowed in 71.8% of the cases. This finding may have important implications for diagnosis and treatment of mental health needs in children with neurological disabilities. Copyright © 2015. Published by Elsevier Ltd.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 04/2015; DOI:10.1016/j.ejpn.2015.04.004 · 1.93 Impact Factor
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    ABSTRACT: The effectiveness of working memory (WM) training programmes is still a subject of debate. Previous reviews were heterogeneous with regard to participant characteristics of the studies included. To examine whether these programmes are of added value for children with learning disabilities (LDs), a systematic meta-analytic review was undertaken focusing specifically on LDs. Thirteen randomised controlled studies were included, with a total of 307 participants (age range = 5.5-17, Mean age across studies = 10.61, SD = 1.77). Potential moderator variables were examined, i.e., age, type of LD, training programme, training dose, design type, and type of control group. The meta-analysis indicated reliable short-term improvements in verbal WM, visuo-spatial WM, and word decoding in children with LDs after training (effect sizes ranged between 0.36 and 0.63), when compared to the untrained control group. These improvements sustained over time for up to eight months. Furthermore, children > 10 years seemed to benefit more in terms of verbal WM than younger children, both immediately after training as well as in the long-term. Other moderator variables did not have an effect on treatment efficacy.
    Neuropsychological Rehabilitation 04/2015; DOI:10.1080/09602011.2015.1026356 · 2.07 Impact Factor
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    ABSTRACT: Duchenne muscular dystrophy (DMD) is a recessive hereditary form of muscular dystrophy caused by a mutation in the dystrophin gene on the X chromosome. Clinical observations show that in addition to progressive muscular degeneration, DMD is more often accompanied by neurocognitive symptoms and learning disabilities, especially in automatisation of reading, attention processes, and expressive language skills. Additionally, three studies reported a higher prevalence of epilepsy in DMD, suggesting that the absence of dystrophin might be related to increased CNS excitability. In this article, we aim to review current clinical and experimental evidence for a potential role of brain dystrophin in seizure generation. Copyright © 2015. Published by Elsevier Ltd.
    Neuroscience & Biobehavioral Reviews 02/2015; 51. DOI:10.1016/j.neubiorev.2015.01.023 · 10.28 Impact Factor
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    ABSTRACT: This study reports on the effects of botulinum toxin A (BoNT-A) injections in the upper extremity (UE) of children with unilateral Cerebral Palsy (uCP) combined with bimanual task oriented therapy (BITT) or either treatment modality performed separately on UE range of motion (ROM), spasticity and (functional) strength. Thirty-five children, mean age 7.14 years (SD 2.63) of whom 11 had a Manual Ability Classification Score (MACS) I, 15 MACS II and 9 MACS III, participated. The trial started with four study groups: BoNT-A-only (n = 5), BITT-only (n = 11), BoNT-A + BITT (n = 13), and control (n = 6). Twenty-two children were randomized and, due to recruitment problems 13 children received their parents' preferred treatment: BoNT-A + BITT or BITT-only. Three comparisons were analysed: BITT (BoNT-A + BITT and BITT-only; n = 24) versus no BITT (BoNT-A-only and control; n = 11), BoNT-A (BoNT-A-only and BoNT-A + BITT; n = 18) versus no BoNT-A (BITT-only and control; n = 17), and the additional effect of BoNT-A (BoNT-A + BITT versus BITT-only). BoNT-A significantly decreased key grip strength and finger flexion tone, had a clinically relevant (additional) positive effect on active thumb abduction and supination and a significantly negative effect on unilateral functional strength. BITT + BoNT-A significantly increased active supination. BITT reduced elbow flexor tone and BITT-only resulted in more improvement than BoNT-A + BITT in functional unimanual and, to a lesser extent, in bimanual grip strength. In comparison with BoNT-A + BITT, BITT-only gives more improvement on functional grip strength and, therefore, could possibly increase bimanual performance. In this case, the (additional) role of BoNT-A may be an increase in active supination and thumb abduction. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 01/2015; 19(3). DOI:10.1016/j.ejpn.2015.01.004 · 1.93 Impact Factor
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    ABSTRACT: Therapeutic hypothermia has become a standard neuroprotective treatment in term newborn infants following perinatal asphyxia. Hypothermia-induced changes in the reactivity of the vessels supplying the brain might play a role in its therapeutic or side effects. We investigated the putative age-related changes and the effect of clinically relevant cooling (33oC) on the reactivity of the newborn rat carotid artery. Carotid artery rings from 2-3 d-old and 9-10 d-old rats were mounted in myographs and studied at 33 and 37oC. Hypothermia did not significantly affect the contractions induced by KCl and U46619, nor the relaxations induced by acetylcholine (ACh), the nitric oxide (NO) donor sodium nitroprusside (SNP), the NO-independent stimulator of soluble guanylate cyclase (sGC) BAY 41-2272, the β-adrenoceptor agonist isoproterenol, the adenylate cyclase activator forskolin, and acute hypoxia (PO2 3 kPa). The relaxations induced by ACh, isoproterenol, the β2-adrenoceptor agonist salbutamol, the β3-adrenoceptor agonist CL-316243 and acute hypoxia increased with postnatal age and were impaired by endothelium removal or by inhibition of NO synthase (L-NAME) or sGC (ODQ). In contrast, the relaxations induced by SNP, BAY 41-2272 and forskolin were endothelium-independent and did not change with age. In conclusion, mild hypothermia (33oC) does not affect the reactivity of neonatal rat carotid arteries. Our data suggest a reduced NO bioavailability in the carotid artery during the first days of life. This transient reduction in endothelium-dependent relaxation might play a role in the adaptation of the circulatory system to birth and in the neonatal vascular response to insults such as hypoxia.
    CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 01/2015; 14(1). DOI:10.2174/1871527314666150116122709 · 2.70 Impact Factor
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    ABSTRACT: Objective: To better understand the inflammatory response in the central nervous system (CNS) after lipopolysaccharide (LPS)-induced chorioamnionitis. Study design: Fetal sheep were exposed to intra-amniotic LPS 2 or 14 days before preterm delivery at 125 days of gestation. mRNA levels of cytokines, TLRs and anti-oxidants were determined in different CNS regions. Results: Interleukin 1β expression increased in hippocampus, cortex and cerebellum 2 days after LPS exposure, while Interleukin 8 expression increased in the periventricular white matter as well. Expression returned back to control levels after 14 days. Tumor necrosis factor-α expression increased in hippocampus and cortex after 2 days. Toll like receptor 4 expression was upregulated in all grey matter regions 2 and 14 days after exposure. Glutathione s-transferase mRNA levels were lower after 2 and 14 days in all grey matter regions. Conclusion: Intra-amniotic LPS exposure causes acute and region-specific changes in inflammatory markers in the fetal brain, with grey matter being more affected than white matter.
    CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 01/2015; 14(1). DOI:10.2174/1871527314666150116120029 · 2.70 Impact Factor
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    ABSTRACT: The Racine scale is a 5-point seizure behavior scoring paradigm used in the amygdala kindled rat. Though this scale has been applied widely in experimental epilepsy research, studies of reproducibility are rare. The aim of the current study was, therefore, to assess its interobserver variability and intraobserver variability. A video database set was acquired in the course of amygdala kindling of 67 Wistar rats. Six blinded observers received scoring instructions and then viewed a set of 15 random videos (session #1). Next, each observer scored 379 to 1048 additional videos (session #2) and finally scored the same set of 15 videos again (session #3). Scores included the occurrence of seizures (yes or no), the total seizure time (start of stimulus until the absence of seizure behavior), and the highest Racine stage. Interobserver variability and intraobserver variability were assessed in and between sessions #1 and #3 using a 2-way mixed intraclass correlation or Cohen's kappa depending on the variable. Interobserver agreement in session #1 was 0.664 for seizure occurrence, 0.861 for total seizure time, and 0.797 for the highest Racine stage. In session #3, interobserver agreement on seizure occurrence declined to 0.492, total seizure time declined to 0.625, and agreement for the highest Racine stage was 0.725. Interobserver agreement was scored insufficiently on focal R2 seizures in both sessions (0.287 and 0.182). Intraobserver agreement reached >0.80 agreement for seizure occurrence, highest seizure score, and total seizure time in 3 out of 4 observers. Racine's scale stage 2 seizure scores were only 0.135 in one observer but 0.650, 0.810, and 0.635 in the other observers. Overall, interobserver agreement and intraobserver agreement in scoring with Racine's scale were adequate. However, because interobserver agreement declined after a period of individually scoring videos, we suggest periodic repetition of the standardized instruction in the course of evaluating videos in order to ensure reproducible results. Copyright © 2014 Elsevier Inc. All rights reserved.
    Epilepsy & Behavior 12/2014; 42C:10-13. DOI:10.1016/j.yebeh.2014.10.030 · 2.06 Impact Factor
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    ABSTRACT: Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE), but its aetiology is unknown. MRI scans often reveal no structural brain abnormalities that could explain the cognitive impairment. This does not exclude more subtle morphological abnormalities that can only be detected by automated morphometric techniques.
    Acta Neurologica Scandinavica 09/2014; DOI:10.1111/ane.12283 · 2.44 Impact Factor
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    ABSTRACT: Background The mechanism of action of vagus nerve stimulation (VNS) in intractable epilepsy is not entirely clarified. It is believed that VNS causes alterations in cytokines, which can lead to rebalancing the release of neurotoxic and neuroprotective tryptophan metabolites. We aimed to evaluate VNS effects on tryptophan metabolites and on epileptic seizures and investigated whether the antiepileptic effectiveness correlated with changes in tryptophan metabolism. Methods Forty-one children with intractable epilepsy were included in a randomized, active-controlled, double-blind study. After a baseline period of 12 weeks, all children underwent implantation of a vagus nerve stimulator and entered a blinded active-controlled phase of 20 weeks. Half of the children received high-output (therapeutic) stimulation (n = 21), while the other half received low-output (active control) stimulation (n = 20). Subsequently, all children received high-output stimulation for another 19 weeks (add-on phase). Tryptophan metabolites were assessed in plasma and cerebrospinal fluid (CSF) by use of liquid chromatography–tandem mass spectrometry (LC–MS/MS) and compared between high- and low-output groups and between the end of both study phases and baseline. Seizure frequency was recorded using seizure diaries. Mood was assessed using Profile of Mood States (POMS) questionnaires. Results Regarding tryptophan metabolites, anthranilic acid (AA) levels were significantly higher at the end of the add-on phase compared with baseline (p = 0.002) and correlated significantly with improvement of mood (τ = − 0.39, p = 0.037) and seizure frequency reduction (τ = − 0.33, p < 0.01). No significant changes were found between high- and low-output groups regarding seizure frequency. Conclusion Vagus nerve stimulation induces a consistent increase in AA, a neuroprotective and anticonvulsant tryptophan metabolite. Moreover, increased AA levels are associated with improvement in mood and reduction of seizure frequency.
    Epilepsy & Behavior 08/2014; 37:133–138. DOI:10.1016/j.yebeh.2014.06.001 · 2.06 Impact Factor
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    ABSTRACT: It is unclear to what extent neuropathological changes contribute to brain inflammation observed in temporal lobe epilepsy (TLE). Here, we compared cytokine levels between histopathologically-confirmed sclerotic hippocampi and histopathologically-confirmed normal hippocampi from TLE patients. We analyzed a similar cytokine panel in hippocampi from amygdala-kindled rats and we evaluated neuropathological changes by immunohistochemistry. In TLE patients, cytokine levels were not significantly different between sclerotic and non-sclerotic hippocampi. Though kindling resulted in increased astrocyte activation, cytokine levels and microglia activation were unchanged. These results suggest that the chronic epileptic state in TLE can also occur in the absence of intracerebral inflammation. Highligths •HS in TLE patients is not associated with a sustained brain inflammatory response.•Amygdala kindled seizures are not associated with a sustained inflammatory response.•Brain inflammation is not necessarily present in temporal lobe epilepsy.
    Journal of neuroimmunology 06/2014; DOI:10.1016/j.jneuroim.2014.03.016 · 2.79 Impact Factor
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    ABSTRACT: Despite efforts to reduce mortality caused by stroke and perinatal asphyxia, these are still the 2(nd) largest cause of death worldwide in the age groups they affect. Furthermore, survivors of cerebral hypoxia-ischemia often suffer neurological morbidities. A better understanding of pathophysiological mechanisms in focal and global brain ischemia will contribute to the development of tailored therapeutic strategies. Similarly, insight in molecular pathways involved in preconditioning-induced brain protection will provide possibilities for future treatment. Microarray technology is a great tool for investigating large scale gene expression, and has been used in many experimental studies of cerebral ischemia and preconditioning to unravel molecular (patho-) physiology. However, the amount of data across microarray studies can be daunting and hard to interpret which is why we aim to provide a clear overview of available data in experimental rodent models. Findings for both injurious ischemia and preconditioning are reviewed under separate subtopics such as cellular stress, inflammation, cytoskeleton and cell signaling. Finally, we investigated the transcriptome signature of brain protection across preconditioning studies in search of transcripts that were expressed similarly across studies. Strikingly, when comparing genes discovered by single-gene analysis we observed only 15 genes present in two studies or more. We subjected these 15 transcripts to DAVID Annotation Clustering analysis to derive their shared biological meaning. Interestingly, the MAPK signaling pathway and more specifically the ERK1/2 pathway geared toward cell survival/proliferation was significantly enriched. To conclude, we advocate incorporating pathway analysis into all microarray data analysis in order to improve the detection of similarities between independently derived datasets.
    Brain research 04/2014; DOI:10.1016/j.brainres.2014.04.001 · 2.83 Impact Factor
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    ABSTRACT: Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE). Its etiology remains unknown. With diffusion tensor imaging, we have studied cerebral white matter properties and associations with cognitive functioning in children with FLE and healthy controls. Thirty children aged 8-13 years with FLE of unknown cause and 39 healthy age-matched controls underwent neuropsychological assessment, structural and diffusion-weighted brain MRI. Patients were grouped as cognitively impaired or unimpaired, and their white matter diffusion properties were compared with the controls. Children with FLE had reduced apparent diffusion coefficients in various posteriorly located tract bundles, a reduced fractional anisotropy (FA) of the white matter tract between the right frontal and right occipital lobe, and smaller volumes of several collections of interlobar bundle tracts, compared with controls. The cognitively impaired patient group demonstrated significant increases in FA of the white matter of both occipital lobes, a reduced FA of white matter tract bundles between the right frontal and both left occipital lobe and subcortical white matter area, and smaller volumes of two collections of tract bundles connecting the frontal lobe with the temporal and parietal lobes, compared with controls. Children with FLE had white matter abnormalities mainly in posterior brain regions, not confined to the area of the seizure focus. Cognitively impaired children with FLE showed the most pronounced white matter abnormalities. These possibly reflect disturbed maturation and might be part of the etiology of the cognitive impairment.
    Acta Neurologica Scandinavica 09/2013; DOI:10.1111/ane.12183 · 2.44 Impact Factor
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    ABSTRACT: Little is known about the long-term effects of Continuous intrathecal Baclofen (CITB) therapy in non-ambulant children with intractable spastic Cerebral Palsy (CP). To determine whether short-term beneficial effects of CITB therapy are present at the long-term, and whether caregivers would choose CITB therapy for their child again considering the advantages and disadvantages encountered over the years. Long-term follow-up data were obtained of the children whom had previously participated in a RCT on CITB by the Dutch Study Group on Spasticity. Quality of life (QoL) was assessed by the Child Health Questionnaire (CHQ), current satisfaction with CITB was measured by use of a Visual Analogue Scale regarding previously set treatment goals, functioning in daily living was determined by a questionnaire concerning functioning of the child, and possible detrimental effects of CITB therapy encountered over the years were noted. All data were acquired via interview of the caregivers. All 17 children of the former trial participated in this study. Previously identified significant positive effects on pain (CHQ 46.8 vs. 74.38, p = 0.002; VAS 2.4 vs. 8.01, p = 0.02), ease of care (VAS 2.0 vs. 7.26, p = 0.00), and mental health (CHQ 67.2 vs. 75.94, p = 0.010) were still present at the end of the trial. Novel significant positive effects were noted at six to nine years follow-up, i.e. significantly improved scores on the Parent Impact - Emotional subscale (CHQ 66.0 vs. 78.2, p = 0.008), Parent Impact - Time subscale (CHQ 68.9 vs. 91.72, p = 0.002), and the Physical Summary (CHQ 17.6 vs. 27.4, p = 0.019) compared to baseline. Ninety-four percent of the caregivers would choose CITB treatment again for their child again. The beneficial effects of CITB are present at the long term and caregiver satisfaction is high.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 07/2013; 17(6). DOI:10.1016/j.ejpn.2013.06.003 · 1.93 Impact Factor
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    ABSTRACT: Based on the assumption that children with spinal dysraphism are exposed to a large amount of ionising radiation for diagnostic purposes, our objective was to estimate this exposure, expressed in cumulative effective dose. Retrospective cohort study. The Netherlands. 135 patients with spinal dysraphism and under 18 years of age treated at our institution between 1991 and 2010. A total of 5874 radiological procedures were assessed of which 2916 (49.6%) involved ionising radiation. Mean cumulative effective dose of a child with spinal dysraphism during childhood was 23 mSv, while the individual cumulative effective dose ranged from 0.1 to 103 mSv. Although direct radiography accounted for 81.7% of examinations, the largest contributors to the cumulative effective dose were fluoroscopic examinations (40.4% of total cumulative effective dose). Exposure to ionising radiation and associated cancer risk were lower than expected. Nevertheless, the use of ionising radiation should always be justified and the medical benefits should outweigh the risk of health detriment, especially in children.
    Archives of Disease in Childhood 07/2013; DOI:10.1136/archdischild-2012-303621 · 2.91 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Sprengel's deformity, a rare congenital malformation of the scapula, may be observed in combination with spinal dysraphism. The co-occurrence of these malformations suggests an unknown shared etiology. Therefore, we reviewed the medical records of eight children presenting with both malformations and performed a review of the literature. PATIENTS AND METHODS: Databases from four university medical centers were searched for children presenting between 1992 and 2012 with spinal dysraphism and a Sprengel's deformity. CONCLUSION: The combination of spinal dysraphism and Sprengel's deformity is rare, and is associated with segmentation defects of the spine and ribs. Although the etiology of both spinal dysraphism and Sprengel's deformity remains unclear, all deformities of the spine, ribs, and shoulder might result from a common genetic defect affecting somitogenesis.
    Child s Nervous System 02/2013; DOI:10.1007/s00381-013-2057-0 · 1.16 Impact Factor
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    ABSTRACT: BACKGROUND: In clinical practice, Rolandic epilepsy is in many cases associated with developmental language impairment. However, from the literature it is unclear exactly which domains are affected; A wide variety of investigations are reported that each provide a different representation of language performance in these patients. AIMS: The aim of this study is to compare performance on the language domains between children with Rolandic epilepsy and healthy controls. METHODS: Prospective study of children with Rolandic epilepsy compared to healthy controls. 25 children (mean age 136.6 months, SD 23.0) with Rolandic epilepsy and 25 age-matched healthy controls were tested on their language function using the CELF-4 (Clinical evaluation of Language Fundamentals, Dutch edition). The healthy control were not matched regard to other important factors, particularly educational attainment and co-morbidity. Expressive language, receptive language, language content, language structure and language working memory were tested. RESULTS: In children with Rolandic epilepsy, the core language score was significant lower compared with healthy controls. They scored specifically lower on the receptive language index and language content index (both p = 0.002). A trend towards decreased expressive language index was observed (p = 0.054). Language structure and language working memory were in the normal range. CONCLUSION: Language was found to be impaired in children with typical Rolandic epilepsy. Especially semantic language processing including receptive language and language content was significantly impaired. The common denominator of these functions is semantic language processing.
    European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 02/2013; DOI:10.1016/j.ejpn.2013.01.001 · 1.93 Impact Factor
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    ABSTRACT: Purpose:  Cognitive impairment is frequent in children with frontal lobe epilepsy (FLE), but its etiology is unknown. With functional magnetic resonance imaging (fMRI), we have explored the relationship between brain activation, functional connectivity, and cognitive functioning in a cohort of pediatric patients with FLE and healthy controls. Methods:  Thirty-two children aged 8-13 years with FLE of unknown cause and 41 healthy age-matched controls underwent neuropsychological assessment and structural and functional brain MRI. We investigated to which extent brain regions activated in response to a working memory task and assessed functional connectivity between distant brain regions. Data of patients were compared to controls, and patients were grouped as cognitively impaired or unimpaired. Key Findings:  Children with FLE showed a global decrease in functional brain connectivity compared to healthy controls, whereas brain activation patterns in children with FLE remained relatively intact. Children with FLE complicated by cognitive impairment typically showed a decrease in frontal lobe connectivity. This decreased frontal lobe connectivity comprised both connections within the frontal lobe as well as connections from the frontal lobe to the parietal lobe, temporal lobe, cerebellum, and basal ganglia. Significance:  Decreased functional frontal lobe connectivity is associated with cognitive impairment in pediatric FLE. The importance of impairment of functional integrity within the frontal lobe network, as well as its connections to distant areas, provides new insights in the etiology of the broad-range cognitive impairments in children with FLE.
    Epilepsia 12/2012; DOI:10.1111/epi.12044 · 4.58 Impact Factor
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    10/2012; 29(3):201-207. DOI:10.5835/jecm.omu.29.03.007
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    ABSTRACT: In a rat model of global fetal and perinatal asphyxia, we investigated if asphyxia and long-lasting brain tolerance to asphyxia (preconditioning) are mediated by modifications in inflammatory cytokines and ceramide metabolism genes in prefrontal cortex, hippocampus and caudate-putamen at the age of 8months. Most significant changes were found in prefrontal cortex, with reduced LAG1 homolog ceramide synthase 1 expression after both types of asphyxia. Additionally, sphingosine kinase 1 was upregulated in those animals that experienced the combination of fetal and perinatal asphyxia (preconditioning), suggesting increased cell proliferation. While cytokine levels are normal, levels of ceramide genes were modulated both after fetal and perinatal asphyxia in the adult prefrontal cortex. Moreover, the combination of two subsequent asphyctic insults provides long-lasting neuroprotection in the prefrontal cortex probably by maintaining normal apoptosis and promoting cell proliferation. Better understanding of the effects of asphyxia on ceramide metabolism will help to understand the changes leading to brain tolerance and will open opportunities for the development of new neuroprotective therapies.
    Journal of neuroimmunology 10/2012; 255(1-2). DOI:10.1016/j.jneuroim.2012.09.011 · 2.79 Impact Factor
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    ABSTRACT: Vagus nerve stimulation (VNS) is a moderately effective treatment for intractable epilepsy. However, the mechanism of action is poorly understood. The effect of left VNS in amygdala kindled rats was investigated by studying changes in nNOS and ΔFos B expression in primary and secondary vagus nerve projection nuclei: the nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus nerve (DMV), parabrachial nucleus (PBN) and locus coeruleus (LC). Rats were fully kindled by stimulation of the amygdala. Subsequently, when the fully kindled state was reached and then maintained for ten days, rats received a single 3-min train of VNS starting 1min prior to the kindling stimulus and lasting for 2min afterwards. In control animals the vagus nerve was not stimulated. Animals were sacrificed 48h later. The brainstems were stained for neuronal nitric oxide synthase (nNOS) and ΔFos B. VNS decreased seizure duration with more than 25% in 21% of rats. No VNS associated changes in nNOS immunoreactivity were observed in the NTS and no changes in ΔFos B were observed in the NTS, PBN, or LC. High nNOS immunopositive cell densities of >300cells/mm(2) were significantly more frequent in the left DMV than in the right (χ(2)(1)=26.2, p<0.01), independent of whether the vagus nerve was stimulated. We conclude that the observed nNOS immunoreactivity in the DMV suggests surgery-induced axonal damage. A 3-min train of VNS in fully kindled rats does not affect ΔFos B expression in primary and secondary projection nuclei of the vagus nerve.
    Journal of chemical neuroanatomy 09/2012; 46(1-2). DOI:10.1016/j.jchemneu.2012.09.004 · 2.52 Impact Factor

Publication Stats

2k Citations
461.28 Total Impact Points

Institutions

  • 1995–2015
    • Maastricht University
      • • Department of Neurology
      • • MHeNS School for Mental Health and Neuroscience
      • • GROW School for Oncology & Developmental Biology
      • • Department of Psychiatry & Neuropsychology
      Maestricht, Limburg, Netherlands
  • 1989–2015
    • Maastricht Universitair Medisch Centrum
      • Central Diagnostic Laboratory
      Maestricht, Limburg, Netherlands
  • 2011
    • Kempenhaeghe
      Heeze, North Brabant, Netherlands
  • 2007
    • Sahlgrenska University Hospital
      Goeteborg, Västra Götaland, Sweden
  • 1990
    • Katholieke Hogeschool Limburg
      Limburg, Walloon Region, Belgium
  • 1988
    • Ear, Nose and Throat Institute
      Alabama, United States
  • 1985–1986
    • Universitair Ziekenhuis Leuven
      • Department of Pedriatrics
      Louvain, Flanders, Belgium
    • Catholic University of Louvain
      Лувен-ла-Нев, Walloon, Belgium
  • 1984–1985
    • University of Leuven
      • Department of Human Genetics
      Louvain, Flemish, Belgium