Fig. 1. Local inhibition of metalloprotease activity in the injured cortex increases the number of neural progenitors and limits their glial differentiation.

a–c Representative confocal (a, b) and fluorescence (c) microscopy images of the area surrounding cortical lesions in mice locally-infused with vehicle or the metalloprotease inhibitor GM6001 (50 μM). Mechanical cortical lesions were unilaterally performed in the primary motor cortex of adult mice, and minipumps were implanted to locally deliver GM6001 or vehicle for 14 or 28 days; at 14 days post-injury (dpi), all mice were intraperitoneally injected with BrdU to label proliferating cells. Mice were sacrificed either at the end of that day (c14 dpi groups) or 14 days later (c14+14 dpi groups). Dotted lines delineate cortical lesion borders. Arrows indicate cells double-labeled for BrdU/GFAP (b) or BrdU/nestin (c). Scale bar = 50 µm. d Quantification of BrdU⁺ cells/mm³ in the perilesional area of the indicated animal groups. e Graph shows the percentage of BrdU⁺ cells that coexpressed GFAP in the perilesional area. f Graph shows the percentage of perilesional area occupied by GFAP⁺ labeling (GFAP burden). g Quantification of nestin⁺ cells/mm³ in the perilesional area of the indicated animal groups. h Percentage of BrdU⁺ cells that coexpressed nestin in the perilesional area. Data shown are the mean ± S.E.M.; n = 3–6 animals per group. Statistical analysis: ANOVA and Bonferroni posttest; *p < 0.05 when compared to vehicle-treated mice; ^†p < 0.05 when compared to the c14 dpi group. L lesion