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Publications Developmental disorders

Here you can find some of the top publications from our research team:

Cora Nijboer

van Tilborg E, Achterberg EJM, van Kammen CM, van der Toorn A, Groenendaal F, Dijkhuizen RM, Heijnen CJ, Vanderschuren LJMJ, Benders MNJL, Nijboer CHA. Combined fetal inflammation and postnatal hypoxia causes myelin deficits and autism-like behavior in a rat model of diffuse white matter injury. Glia. 2018 Jan;66(1):78-93.

Diffuse white matter injury (WMI) is a serious problem in extremely preterm infants, and is associated with adverse neurodevelopmental outcome, including cognitive impairments and an increased risk of autism-spectrum disorders. In the present study, we developed a multiple-hit animal model of diffuse WMI by combining fetal inflammation and postnatal hypoxia in rats. We characterized the effects on white matter development and functional outcome by immunohistochemistry, MRI and behavioral paradigms. The combination of fetal inflammation and postnatal hypoxia in rats induces a pattern of brain injury and functional impairments that closely resembles the clinical situation of diffuse WMI.

Jeroen Dudink & Freek Hoebeek

Pieterman K, Batalle D, Dudink J, Tournier JD, Hughes EJ, Barnett M, Benders MJ, Edwards AD, Hoebeek FE, Counsell SJ. Cerebello-cerebral connectivity in the developing brain. Brain Struct Funct. 2017 May;222(4):1625-1634.

In this study we developed a novel method to assess cortico-ponto-cerebellar (CPC) and cerebello-thalamo-cortical (CTC) white matter tracts during brain development using high angular resolution diffusion imaging (HARDI) in vivo during the early stages of development. The ability to assess cerebellar connectivity during this critical developmental period helps improve our understanding of the role of the cerebellum in a wide range of neuromotor and neurocognitive disorders.

Jeroen Pasterkamp & Elly Hol

Ormel PR, Vieira de Sá R, van Bodegraven EJ, Karst H, Harschnitz O, Sneeboer MAM, Johansen LE, van Dijk RE, Scheefhals N, Berdenis van Berlekom A, Ribes Martínez E, Kling S, MacGillavry HD, van den Berg LH, Kahn RS, Hol EM, de Witte LD, Pasterkamp RJ. Microglia innately develop within cerebral organoids. Nat Commun. 2018 Oct 9;9(1):4167


Cerebral organoids are 3D stem cell-derived models that can be utilized to study the human brain. The current consensus is that cerebral organoids consist of cells derived from the neuroectodermal lineage. This limits their value and applicability, as mesodermal-derived microglia are important players in neural development and disease. Remarkably, here we show that microglia can innately develop within a cerebral organoid model and display their characteristic ramified morphology. The transcriptome and response to inflammatory stimulation of these organoid-grown microglia closely mimic the transcriptome and response of adult microglia acutely isolated from post mortem human brain tissue. In addition, organoid-grown microglia mediate phagocytosis and synaptic material is detected inside them. In all, our study characterizes a microglia-containing organoid model that represents a valuable tool for studying the interplay between microglia, macroglia, and neurons in human brain development and disease.

Olaf Verschuren & Marjolein Ketelaars

Smits DW, Gorter JW, Riddell CA, Voorman JM, Rosenbaum PL, Palisano RJ, Walter SD, Hanna SE, van Wely L, Ketelaar M. Mobility and self-care trajectories for individuals with cerebral palsy (aged 1-21 years): a joint longitudinal analysis of cohort data from the Netherlands and Canada.  Lancet Child Adolesc Health. 2019 Aug;3(8):548-557.

Cerebral Palsy (CP) results from an injury to the developing brain. In the early years of life, it is generally not yet clear how a child with CP will develop. A child may develop more slowly or differently in terms of movement, speech, social development and behavior in a highly individual manner. Based on a longitudinal follow-up of 551 children, adolescents and young adults, developmental trajectories for self-care and mobility have been distinguished for subgroups of CP. This enables prognosis and planning of interventions.

Marijke Achterberg, Louk Vanderschuren & Heidi Lesscher

Nijhof SL, Vinkers CH, van Geelen SM, Duijff SN, Achterberg EJM, van der Net J, Veltkamp RC, Grootenhuis MA, van de Putte EM, Hillegers MHJ, van der Brug AW, Wierenga CJ, Benders MJNL, Engels RCME, van der Ent CK, Vanderschuren LJMJ, Lesscher HMB. Healthy play, better coping: The importance of play for the development of children in health and disease. Neurosci Biobehav Rev. 2018 Dec;95:421-429.

Play is of vital importance for the healthy development of children. From a developmental perspective, play offers ample physical, emotional, cognitive, and social benefits. It allows children and adolescents to develop motor skills, experiment with their (social) behavioural repertoire, simulate alternative scenarios, and address the various positive and negative consequences of their behaviour in a safe and engaging context. Children with a chronic or life-threatening disease may face obstacles that negatively impact play and play development, possibly impeding developmental milestones, beyond the actual illness itself. Currently, there is limited understanding of the impact of (1) aberrant or suppressed play and (2) play-related interventions on the development of chronic diseased children. We argue that stimulating play behaviour enhances the adaptability of a child to a (chronic) stressful condition and promotes cognitive, social, emotional and psychomotor functioning, thereby strengthening the basis for their future health. Systematic play research will help to develop interventions for young patients, to better cope with the negative consequences of their illness and stimulate healthy development.