Fig. 1
IGF1 overexpression enhances long-term posttraumatic neurogenesis and rescues trauma-induced reduction of differentiated mature neuron pool. Controlled cortical impact (CCI) enhanced proliferation in both wildtype (WT) and IGF1 overexpressing (IGFtg) mice. Cells dividing within 7 days following surgery were detected at 6 weeks after injury in the granule cell layer (GCL), molecular layer (ML) and hilus (HL) using bromodeoxyuridine (BrdU, red) immunolabelling of (a, b) sham controls, (c, d) injured WT, and (e, f) injured IGFtg mice. DAPI label is shown in blue. A subset of BrdU+ cells in the GCL colabelled with the mature neuron-specific protein, Neuronal Nuclei (NeuN, green) (b, d, f). Examples of colabelled cells are noted by arrows. (g) The phenotype of posttrauma-proliferated cells was confirmed by 3D reconstruction of confocal images, as demonstrated in high-magnification images for the cells in the red box in (f). The scale bar represents 50 μm in A, C and E, 10 μm in B, D and F, and 5 μm in G. (h) The density of BrdU+ cells (cells/mm3) within the GCL was increased in injured WT and injured IGFtg mice relative to their respective sham controls. (i) Following injury, IGF1 overexpression increased the density (cells/mm3) of surviving posttrauma-born neurons (NeuN+BrdU+) in the GCL. (j) Trauma reduced the proportion of proliferated progenitors that matured into end-stage neurons in WT mice but not in IGF1tg mice. Data are presented as mean + SEM; n = 3 sham /genotype, n = 8–9 CCI /genotype. One-way ANOVA, followed by Bonferroni’s selected comparisons post-hoc t-tests: *p < 0.05 and **p < 0.01 compared to respective sham group, and &&p < 0.01 and &&&p < 0.001 compared to injured WT