Altered local cerebellar and brainstem development in preterm infants

Stoodley, Catherine J.; Brossard‐Racine, Marie; Kapse, Kushal; Vézina, Gilbert; Murnick, Jonathan; Plessis, Adré J. du; Limperopoulos, Catherine

doi:10.1016/j.neuroimage.2020.116702

Cited by 34 publications

(20 citation statements)

References 80 publications

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“…These infants had a high load of PWMLs, further supporting previous suggestions of a close link between thalamic development and white matter abnormalities, including a previous group analysis of the EPrime dataset 38,41,42 . The cerebellum is one of the most rapidly growing structures during the perinatal period, but altered cerebellar development in preterm infants and its relation to supratentorial brain injury is complex and poorly characterized [43][44][45][46] . We observed significant deviations in cerebellar volume in the absence of structural supratentorial injury in a small proportion of infants in both preterm cohorts.…”

Section: Discussionmentioning

confidence: 99%

Phenotyping the preterm brain: characterising individual deviations from normative volumetric development in two large infant cohorts

Dimitrova

Arulkumaran

Carney

et al. 2020

Preprint

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ObjectivePreterm birth carries a significant risk for atypical development. While studies comparing group means have identified a number of early brain correlates of prematurity, they may ‘average out’ effects significant in a single individual. To understand better the cerebral consequences of prematurity, we created normative ‘growth curves’ characterizing neonatal brain development and explored the effect of preterm birth and related clinical risks in individual infants.MethodsWe used Gaussian process regression to map typical volumetric development in 275 healthy term-born infants, modelling for age at scan and sex. We compared magnetic resonance images of 89 preterm infants (born 28.7–34 weeks gestational age) scanned at term-equivalent age to these normative charts and related deviations from typical volumetric development to both perinatal clinical variables and neurocognitive scores at 18 months. We then tested if this approach can be generalized to an independent dataset of 253 preterm infants (born 28–31.6 weeks gestational age) also scanned at term-equivalent age but using different acquisition parameters and scanner, who were followed-up at 20 months.ResultsIn both preterm cohorts, cerebral atypicalities were widespread and often multiple, but varied highly between individual infants. Deviations from normative brain volumetric development were associated with perinatal factors including respiratory support, nutrition and postnatal growth, as well as with later neurocognitive outcome.ConclusionGroup-level understanding of the preterm brain might disguise a large degree of individual differences. We provide a method and a normative dataset for clinicians and researchers to profile the individual brain. This will allow a more precise characterization of the cerebral consequences of prematurity and improve the predictive power of neuroimaging.

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Section: Discussionmentioning

confidence: 99%

Phenotyping the preterm brain: characterising individual deviations from normative volumetric development in two large infant cohorts

Dimitrova

Arulkumaran

Carney

et al. 2020

Preprint

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“…Despite the prevalence of cerebellar injury in preterm born infants 5, 6, 24, 75, 76 and the links between these insults and poor outcomes in preterm born infants 77, 78 , there is not many studies focused on the cerebellum in models of preterm brain injury. We have addressed this issue and we have documented by MRI that in our model of inflammation-associated encephalopathy of prematurity that there is a global change in absolute volumes of the mouse brain, with a specific loss of cerebellar volume into adulthood.…”

Section: Discussionmentioning

confidence: 99%

A unique cerebellar pattern of microglia activation in a mouse model of encephalopathy of prematurity

Klein¹,

Steenwinckel

Fleiss

et al. 2021

Preprint

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Preterm infants often show pathologies of the cerebellum, which are associated with impaired motor performance, lower IQ and poor language skills at school ages. Because 1 in 10 babies is born preterm cerebellar injury is a significant clinical problem. The causes of cerebellar damage are yet to be fully explained. Herein, we tested the hypothesis that perinatal inflammatory stimuli may play a key role in cerebellar injury of preterm infants. We undertook our studies in an established mouse model of inflammation-induced encephalopathy of prematurity driven by systemic administration of the prototypic pro-inflammatory cytokine interleukin-1β (IL-1β). Inflammation is induced between postnatal day (P) 1 to day 5, timing equivalent to the last trimester for brain development in humans the period of vulnerability to preterm birth related brain injury. We investigated acute and long-term consequences for the cerebellum on brain volume expansion, oligodendroglial maturation, myelin levels and the microglial transcriptome. Perinatal inflammation induced global mouse brain volume reductions, including specific grey and white matter volume reductions in cerebellar lobules I and II (5% FDR) in IL-1β versus control treated mice from P15 onwards. Oligodendroglia damage preceded the MRI-detectable volume changes, as evidenced by a reduced proliferation of OLIG2+ cells at P10 and reduced levels of the myelin proteins MOG, MBP and MAG at P10 and P15. Increased density of Iba1+ cerebellar microglia was observed at P5 and P45, with evidence for increased microglial proliferation at P5 and P10. Comparison of the transcriptome of microglia isolated from P5 cerebelli and cerebrum revealed significant enrichment of pro-inflammatory markers in microglia from both regions, but in the cerebellum microglia displayed a unique type I interferon signalling dysregulation. Collectively, these data suggest that in our model that systemic inflammation causes chronic activation of microglia and maldevelopment of cerebellum that includes myelin deficits which is driven in the cerebellum by type I interferon signalling. Future protective strategies for preterm infants should consider sustained type I interferon signalling driven cerebellar inflammation as an important target.

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“…It is noteworthy mentioning that CH may globally involve the cerebellum (affecting equally the hemispheres and the vermis) or, in contrast, may present with a volume loss of both the hemispheres with or without vermis abnormalities ( Tam, 2018 ). In this regard, a recent study carried out by Wu et al (2020) compared preterm babies and healthy controls, demonstrating that prematures show not only smaller volumes (global and regional), but also different shapes both of cerebellum and brainstem, even when a structural injury of these areas fails to be detected by MRI scans. Even if numerous lesional patterns have been reported, the most typically observed includes bilateral and symmetric involvement of the two cerebellar hemispheres, associated with smaller pons, and supratentorial injuries ( Pierson and Al Sufiani, 2016 ).…”

Section: Cerebellar Neuropathologymentioning

confidence: 99%

Cerebellum and Prematurity: A Complex Interplay Between Disruptive and Dysmaturational Events

Spoto

Amore

Vetri

et al. 2021

Front. Syst. Neurosci.

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The cerebellum plays a critical regulatory role in motor coordination, cognition, behavior, language, memory, and learning, hence overseeing a multiplicity of functions. Cerebellar development begins during early embryonic development, lasting until the first postnatal years. Particularly, the greatest increase of its volume occurs during the third trimester of pregnancy, which represents a critical period for cerebellar maturation. Preterm birth and all the related prenatal and perinatal contingencies may determine both dysmaturative and lesional events, potentially involving the developing cerebellum, and contributing to the constellation of the neuropsychiatric outcomes with several implications in setting-up clinical follow-up and early intervention.

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Altered local cerebellar and brainstem development in preterm infants

Cited by 34 publications

References 80 publications

Phenotyping the preterm brain: characterising individual deviations from normative volumetric development in two large infant cohorts

Phenotyping the preterm brain: characterising individual deviations from normative volumetric development in two large infant cohorts

A unique cerebellar pattern of microglia activation in a mouse model of encephalopathy of prematurity

Cerebellum and Prematurity: A Complex Interplay Between Disruptive and Dysmaturational Events

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