RESEARCH PROJECT THE VULNERABLE PRETERM CEREBELLUM: ELUCIDATING MECHANISMS AND CONSEQUENCES OF INJURY Catherine Limperopoulos, Ph.D., Project Director Director, MRI Research of the Developing Brain Director, Advanced Pediatric Brain Imaging Research Laboratory Diagnostic Imaging and Radiology Children?s National Health System Louis-Gilbert Vzina, Ph.D. Director, Pediatric Neuroradiology Children?s National Health System Adre J. du Plessis, MBchB, MPH Chief, Fetal and Transitional Medicine Children National Health System Penny Glass, Ph.D. Director, Child Development Center Center for Neuroscience and Behavioral Medicine Children?s National Health System Lauren Kenworthy, Ph.D. Pediatric Neuropsychologist Director, Center for Autism Spectrum Disorders Children?s National Health System Zungho (Wesley) Zun, Ph.D. MRI Physicist/Research Faculty Advanced Pediatric Brain Imaging Research Laboratory Children?s National Health System Robert J. McCarter Jr., ScD Director of the IDDRC Biostatistics and Informatics Component Head: Research Section of Study Design and Biostatistical Consulting Children?s National Health System Catherine Stoodley, D.Phil. Assistant Professor Psychology and Neuroscience Department American University Abstract Premature birth is a major public health problem, associated with a personal, familial, and societal burden of enormous proportions. The potentially lifelong cognitive, learning and affective-behavioral consequences have become the major determinant of life quality in prematurity survivors, with up to 50% of very premature infants experiencing dysfunction in these domains by school age. Impaired cerebellar development has been recently implicated in this dysfunction. We have described a clinically important, previously under-recognized form of prematurity-related cerebellar parenchymal injury in up to 20% in extremely preterm infants. Recently, our observations have extended beyond the role of parenchymal cerebellar injury to a broader and more prevalent spectrum of cerebellar developmental impairments. We have shown that cerebellar development is (i) markedly accelerated during the third trimester, but (ii) significantly impeded after premature birth, even in the absence of direct cerebellar injury. We refer to this impaired growth as cerebellar developmental impairment (CDI). Complementing this intriguing set of structural observations are our findings of a distinctive long-term neuropsychological profile of cognitive, language, affective and social deficiency, which we have termed the developmental cerebellar cognitive affective disorder. The onset and underlying mechanisms and consequences of prematurity-related CDI remain poorly understood, which in turn have complicated the search for potential therapeutic interventions. We propose to utilize serial, advanced MRI techniques to elucidate the timing, evolution, mechanisms and risk factors of CDI in preterm infants born ?30 weeks gestational age. Our overarching goal is to identify early MR imaging biomarkers of prematurity-related CDI and the associated clinical factors that lead to specific development disabilities. We plan to leverage our large fetal normative database to compare in-utero fetal and ex-utero preterm cerebellar growth trajectories. These findings will inform specific targets, interventions and timing of future neuroprotective strategies, advance clinical practices, and improve neurodevelopmental outcomes.

Public Health Relevance

The Vulnerable Preterm Cerebellum: Elucidating Mechanisms and Consequences of Injury PI: Catherine Limperopoulos, PhD Cerebellar injury has been implicated in the high prevalence of neurodevelopmental disabilities in very premature infants. The goal of this study is to identify early magnetic resonance imaging biomarkers of prematurity-related cerebellar developmental impairment that leads to specific development disabilities. Findings will inform specific targets for future interventions to improve neurodevelopmental outcomes.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZHD1-DSR-H (50))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Children's Research Institute
United States
Zip Code
Basu, Sudeepta K; Ottolini, Katherine; Govindan, Vedavalli et al. (2018) Early Glycemic Profile Is Associated with Brain Injury Patterns on Magnetic Resonance Imaging in Hypoxic Ischemic Encephalopathy. J Pediatr 203:137-143
Sathyanesan, Aaron; Kundu, Srikanya; Abbah, Joseph et al. (2018) Neonatal brain injury causes cerebellar learning deficits and Purkinje cell dysfunction. Nat Commun 9:3235
Uittenbogaard, Martine; Brantner, Christine A; Fang, ZiShui et al. (2018) The m.11778 A?>?G variant associated with the coexistence of Leber's hereditary optic neuropathy and multiple sclerosis-like illness dysregulates the metabolic interplay between mitochondrial oxidative phosphorylation and glycolysis. Mitochondrion :
Sreetama, Sen Chandra; Chandra, Goutam; Van der Meulen, Jack H et al. (2018) Membrane Stabilization by Modified Steroid Offers a Potential Therapy for Muscular Dystrophy Due to Dysferlin Deficit. Mol Ther 26:2231-2242
Smith, Nathan A; Kress, Benjamin T; Lu, Yuan et al. (2018) Fluorescent Ca2+ indicators directly inhibit the Na,K-ATPase and disrupt cellular functions. Sci Signal 11:
Adams, Katrina L; Gallo, Vittorio (2018) The diversity and disparity of the glial scar. Nat Neurosci 21:9-15
Gulinello, Maria; Mitchell, Heather A; Chang, Qiang et al. (2018) Rigor and reproducibility in rodent behavioral research. Neurobiol Learn Mem :
Val, St├ęphanie; Krueger, Anna; Poley, Marian et al. (2018) Nontypeable Haemophilus influenzae lysates increase heterogeneous nuclear ribonucleoprotein secretion and exosome release in human middle-ear epithelial cells. FASEB J 32:1855-1867
Govindan, R B; Massaro, A N; du Plessis, Adre (2018) Ensuring signal quality of cerebral near infrared spectroscopy during continuous longterm monitoring. J Neurosci Methods 309:147-152
Kuo, Che-Ying; Guo, Ting; Cabrera-Luque, Juan et al. (2018) Placental basement membrane proteins are required for effective cytotrophoblast invasion in a three-dimensional bioprinted placenta model. J Biomed Mater Res A 106:1476-1487

Showing the most recent 10 out of 30 publications