The centromedian-parafascicular complex represents a nodal point in the neuronal loop comprising striatum--globulus pallidus--thalamus--striatum. Striatal neurone degeneration is a hallmark in Huntington's disease and we were interested in estimating total neurone and glial number in this thalamic nuclear complex. Serial 500-microns-thick gallocyanin-stained frontal sections of the left hemisphere from six cases of Huntington's disease patients (three females, three males) and six age- and sex-matched controls were investigated applying Cavalieri's principle and the optical disector. Mean neurone number in the controls was 646,952 +/- 129,668 cells versus 291,763 +/- 60,122 in Huntington's disease patients (Mann-Whitney U-test, P < 0.001). Total glial cell number (astrocytes, oligodendrocytes, microglia, and unclassifiable glial profiles) was higher in controls with 9,544,191 +/- 3,028,944 versus 6,961,989 +/- 2,241,543 in Huntington's disease patients (Mann-Whitney U-test, P < 0.021). Considerable increase of fibrous astroglia within the centromedian-parafascicular complex could be observed after Gallyas' impregnation. Most probably this cell type enhanced the numerical ratio between glial number and neurone number (glial index: Huntington's disease patients = 24.4 +/- 8.1; controls = 15.0 +/- 5.2; Mann-Whitney U-test, P < 0.013). The neurone number in the centromedian-parafascicular complex correlated negatively, although statistically not significantly, with the striatal neurone number. This lack of correlation between an 80% neuronal loss in the striatum and a 55% neurone loss in the centromedian-parafascicular complex points to viable neuronal circuits connecting the centromedian-parafascicular complex with cortical and subcortical regions that are less affected in Huntington's disease.
BackgroundGlioblastoma multiforme is the most common lethal brain tumor in human adults, with no major therapeutic breakthroughs in recent decades. Research is based mostly on human tumor cell lines deprived of their organotypic environment or inserted into immune-deficient animals required for graft survival. Here, we describe how glioblastoma specimens obtained from surgical biopsy material can be sectioned and transferred into cultures within minutes.MethodsSlices were kept in 6-well plates, allowing direct observation, application of temozolomide, and irradiation. At the end of experiments, slice cultures were processed for histological analysis including hematoxylin-eosin staining, detection of proliferation (Ki67), apoptosis/cell death (cleaved caspase 3, propidium iodide), DNA double-strand breaks (γH2AX), and neural subpopulations. First clinical trials employed irradiation with the heavy ion carbon for the treatment of glioblastoma patients, but the biological effects and most effective dose regimens remain to be established. Therefore, we developed an approach to expose glioblastoma slice cultures to 12C and X-rays.ResultsWe found preservation of the individual histopathology over at least 16 days. Treatments resulted in activation of caspase 3, inhibition of proliferation, and cell loss. Irradiation induced γH2AX. In line with clinical observations, individual tumors differed significantly in their susceptibility to temozolomide (0.4%–2.5% apoptosis and 1%–15% cell loss).ConclusionGlioblastoma multiforme slice cultures provide a unique tool to explore susceptibility of individual tumors for specific therapies including heavy ions, thus potentially allowing more personalized treatments plus exploration of mechanisms of (and strategies to overcome) tumor resistance.
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