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ItemMR imaging correlates of white-matter pathology in a preterm baboon modelGriffith, JL ; Shimony, JS ; Cousins, SA ; Rees, SE ; McCurnin, DC ; Inder, TE ; Neil, JJ (NATURE PUBLISHING GROUP, 2012-02-01)INTRODUCTION: Cerebral white-matter (WM) abnormalities on magnetic resonance imaging (MRI) correlate with neurodevelopmental disability in infants born prematurely. RESULTS: Quantitative histological measures of WM and ventricular volumes correlated with qualitative MRI scores of WM volume loss and ventriculomegaly. Diffuse astrocytosis was associated with signal abnormality on T(2)-weighted imaging and higher apparent diffusion coefficient in WM. Loss of oligodendrocytes was associated with lower relative anisotropy characterized by higher radial diffusivity values. The relationship between histopathology and MRI abnormalities was more pronounced in animals in the 28 d model, equivalent to the term human infant. DISCUSSION: MRI reflects microstructural and anatomical abnormalities that are characteristic of WM injury in the preterm brain, and these changes are more evident on MRI at term-equivalent postmenstrual age. METHODS: We assessed the histopathological correlates of MRI abnormalities in a baboon model of premature birth. Baboons were delivered at 125 d of gestation (dg, term ~185 dg) and maintained in an animal intensive care unit for 14 (n = 26) or 28 d (n = 17). Gestational control animals were delivered at 140 dg (n = 9) or 153 dg (n = 4). Cerebral WM in fixed brains was evaluated using MRI, diffusion tensor imaging (DTI), and histopathology.
ItemFibroblast Growth Factor-9 Inhibits Astrocyte Differentiation of Adult Mouse Neural Progenitor CellsLum, M ; Turbic, A ; Mitrovic, B ; Turnley, AM (WILEY-BLACKWELL, 2009-08-01)Fibroblast growth factor-9 (FGF9) is expressed in the CNS and is reported to be a mitogen for glial cells, to promote neuronal survival, and to retard oligodendrocyte differentiation. Here we examined the effects of FGF9 on the differentiation, survival, and proliferation of adult neural progenitor cells derived from the adult mouse subventricular zone. FGF9 by itself induced neurosphere proliferation, but its effects were modest compared with those of epidermal growth factor and FGF2. When neurospheres were dissociated and plated for differentiation, FGF9 increased total cell number over time in a dose-dependent manner. Ki67 immunostaining and bromodeoxyuridine incorporation indicated that this was at least partially due to the continued presence of proliferative nestin-positive neural progenitor cells and betaIII tubulin-positive neuronal precursors. FGF9 also promoted cell survival as indicated by a decreased number of TUNEL-positive cells over time. Assessment of differentiation showed that FGF9 increased neuron generation that reflected the increase in total cell number; however, the percentage of progenitor cells differentiating into neurons was slightly decreased. FGF9 had a modest effect on oligodendrocyte generation, although it appeared to slow the maturation of oligodenrocytes at higher concentrations. The most marked effect on differentiation was an almost total lack of glial fibrillary acidic protein (GFAP)-positive astrocytes up to 7 days following FGF9 addition, indicating that astrocyte differentiation was strongly inhibited. Total inhibition required prolonged treatment, although a 1-hr pulse was sufficient for partial inhibition, and bone morphogenic protein-4 could partially overcome the FGF9 inhibition of astrocyte differentiation. FGF9 therefore has multiple effects on adult neural precursor cell function, enhancing neuronal precursor proliferation and specifically inhibiting GFAP expression.