Dataset Information

Quantification of white matter injury following neonatal stroke with serial DTI.

ABSTRACT: Diffusion tensor imaging (DTI) can be used to predict outcome following perinatal arterial ischemic stroke (PAIS), although little is known about white matter changes over time.Infants with PAIS were serially scanned in the neonatal period (n = 15), at 3 mo (n = 16), and at 24 mo (n = 8). Fractional anisotropy (FA) values in five regions of interest (anterior and posterior limb of the internal capsule, corpus callosum, optic radiation, and posterior thalamic radiation) were obtained and compared with FA values of healthy controls and neurodevelopmental outcome.In the neonatal period, no differences in FA values were found. At 3 mo, the six infants who ultimately developed motor deficits showed lower FA values in all affected regions. Four infants developed a visual field defect and showed lower FA values in the affected optic radiation at 3 mo (0.22 vs. 0.29; P = 0.03). Finally, a correlation between FA values of the corpus callosum at 3 mo and the Griffiths developmental quotients was found (r = 0.66; P = 0.03). At 24 mo, a similar pattern was observed.Neonatal FA measurements may underestimate the extent of injury following PAIS. FA measurements at 3 mo could be considered a more reliable predictor of neurodevelopmental outcome and correlate with DTI findings at 24 mo.

SUBMITTER: van der Aa NE

PROVIDER: S-EPMC6117163 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Quantification of white matter injury following neonatal stroke with serial DTI.

van der Aa Niek E NE Northington Frances J FJ Stone Brian S BS Groenendaal Floris F Benders Manon J N L MJ Porro Giorgio G Yoshida Shoko S Mori Susumu S de Vries Linda S LS Zhang Jiangyang J Zhang Jiangyang J

Pediatric research 20130311 6

<h4>Background</h4>Diffusion tensor imaging (DTI) can be used to predict outcome following perinatal arterial ischemic stroke (PAIS), although little is known about white matter changes over time.<h4>Methods</h4>Infants with PAIS were serially scanned in the neonatal period (n = 15), at 3 mo (n = 16), and at 24 mo (n = 8). Fractional anisotropy (FA) values in five regions of interest (anterior and posterior limb of the internal capsule, corpus callosum, optic radiation, and posterior thalamic ra ...[more]

PMID: 23478641

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Project description:Extreme prematurity is a major risk factor for perinatal and neonatal brain injury, and can lead to white matter injury that is a precursor for a number of neurological diseases, including cerebral palsy (CP) and autism. Neuroinflammation, mediated by activated microglia and astrocytes, is implicated in the pathogenesis of neonatal brain injury. Therefore, targeted drug delivery to attenuate neuroinflammation may greatly improve therapeutic outcomes in models of perinatal white matter injury. In this work, we use a mouse model of ischemia-induced neonatal white matter injury to study the biodistribution of generation 4, hydroxyl-functionalized polyamidoamine dendrimers. Following systemic administration of the Cy5-labeled dendrimer (D-Cy5), we demonstrate dendrimer uptake in cells involved in ischemic injury, and in ongoing inflammation, leading to secondary injury. The sub-acute response to injury is driven by astrocytes. Within five days of injury, microglial proliferation and migration occurs, along with limited differentiation of oligodendrocytes and oligodendrocyte death. From one day to five days after injury, a shift in dendrimer co-localization occurred. Initially, dendrimer predominantly co-localized with astrocytes, with a subsequent shift towards microglia. Co-localization with oligodendrocytes reduced over the same time period, demonstrating a region-specific uptake based on the progression of the injury. We further show that systemic administration of a single dose of dendrimer-N-acetyl cysteine conjugate (D-NAC) at either sub-acute or delayed time points after injury results in sustained attenuation of the 'detrimental' pro-inflammatory response up to 9days after injury, while not impacting the 'favorable' anti-inflammatory response. The D-NAC therapy also led to improvement in myelination, suggesting reduced white matter injury. Demonstration of treatment efficacy at later time points in the postnatal period provides a greater understanding of how microglial activation and chronic inflammation can be targeted to treat neonatal brain injury. Importantly, it may also provide a longer therapeutic window.

Dataset Information

Quantification of white matter injury following neonatal stroke with serial DTI.

Publications

Quantification of white matter injury following neonatal stroke with serial DTI.

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