rAAV-transduced v-BMP7 decreases ischemic brain damage. A. Efficient, long-lasting v-BMP2 and v-BMP7 expression eight weeks after rAAV injection into the brains of neonatal mice. Fluorescent immunohistological images of sagittal brain sections are in gray scale. CTX, cortex; HPC, hippocampus; OB, olfactory bulb; LV, epithelium of lateral ventricles. Scale bar, 1 mm. Insets: confocal images of cortical neurons expressing v-BMP2 and v-BMP7. Cellular resolutions show neurons expressing v-BMP2 and v-BMP7 and one v-BMP2 positive astrocyte. Scale bar, 30 μm. B. Top: silver-stained coronal brain sections with marked, unstained infarcts 48 h after MCAO. Bottom: quantification of infarct volumes. The brain edema did not differ between groups. Values are means ± SEM. First experiment (i): v-Venus, n = 8; v-BMP7, n = 9; v-BMP2, n = 12; v-Noggin, n = 7); one-way ANOVA, P = 0.0049, *, p < 0.05 (Tukey’s posthoc test). Second experiment (ii): Ctrl., n = 4; v-Venus, n = 8; v-BMP7, n = 8; one-way ANOVA, P = 0.0265, *, p < 0.05 (Tukey’s posthoc test). C. Virally delivered v-BMP7 had no influence on cerebral blood flow measured by Doppler sonography before and after MCAO in (ii). Values were normalized to Ctrl. before MCAO; means ± SEM. D. The rAAV-expressed v-BMP7 reduced apoptosis after MCAO. Top: apoptotic nuclei were quantified 48 h after MCAO on TUNEL-stained coronal sections in indicated areas. Middle: images of TUNEL- and DAPI-stained (total number of nuclei) brain sections after MCAO in gray-scale. Scale bar, 50 μm. Bottom: quantification of apoptotic nuclei after MCAO was determined in relation to the total number of DAPI stained nuclei in all three indicated areas. Values are means ± SEM (n = 3). One-way ANOVA, P = 0.0002, *, p < 0.05 (Tukey’s posthoc test).
Heinonen et al. BMC Neuroscience 2014 15:38 doi:10.1186/1471-2202-15-38