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The mean cortical thickness was assessed by measuring the distance between external capsule/corpus callosum and dorsal brain surface. For this purpose, a semi-automated macro was implemented in ImageJ (version 1.46, NIH, Bethesda, MD; USA) measuring the cortex thickness perpendicular to a manually generated outline of the white matter. In this procedure the most medial part of the corpus callosum was excluded, because the assumption of a parallel cortex is not met in this region. In detail, in a first step a ��profile image�� is created: A manually generated outline (��Segmented Line�� tool in ImageJ) is used to fit a curve to the center of the corpus callosum using Gaussian combined with Heaviside step function fits. Straight lines, perpendicular to this HSP90 curve and reaching the cortical surface, form the ��profile image��, i.e. the curve is straightened. In a second step, the cortex thickness is measured in the profile image by determining the length of the straight lines perpendicular to the curve crossing the cortex only. This distinction is achieved by submitting the gray scales in the profile image to a Rodbard fitting function. This procedure of cortex thickness determination was performed for the somatosensory cortex in 5�C6 slices. At 3W, 3M and 6M, animals were sacrificed by transcardial perfusion with phosphate buffered solution (PBS) and 4% paraformaldehyde (PFA). Brains were postfixed overnight in 4% PFA before treatment with 30% sucrose. Tissue sections of 40?��m thickness were cut (Microtome, Leica Microsystems, selleck inhibitor Wetzlar, Germany) and preserved at ??20?��C for histological staining. Sections at six selected levels were stained for both myelin and for cell nuclei, using Black-Gold II (BGII) (Schmued et al., 2008), and cresyl violet (CV), respectively (both: EMD Millipore, Billerica, MA, USA). In order to assess the cell and myelin density in the brain, image acquisition and evaluation was conducted with a Keyence BZ9000 fluorescence Etoposide concentration microscope (Keyence, Neu-Isenburg, Germany) with a cell count analysis tool (Keyence). Quantification was based on contrast and color intensity in full-focus projections of images with 20?�� magnification (focal planes of 3?��m). ROIs were chosen in multiple areas: four cortical ROIs per hemisphere, each, in 6 sections (48 in total) and three striatal ROIs per hemisphere, each, in three sections (18 in total). Relative myelin content was defined as the relative area covered by BGII stained processes; cell density was determined as the number of CV stained cell nuclei per area. Longitudinal MRI data was evaluated using repeated measures ANOVA (SPSS version 18, IBM Corp. Armonk, NY, USA) with a repeated within-subject design. Where Mauchly's test indicated that the assumption of sphericity was violated (p?