Figure 2.

Millimeter-scale positioning of NGF-releasing implant. (a) Positioning of NGF-releasing implants. In both sets of experiments (Tx¹ and Tx²), the same anatomical treatment site was stereotactically defined: 1 mm rostral to the bregma and 2–3 mm to the right of the bregma (star). In Tx¹, the site of treatment was undisturbed and contained a native population of cells. In Tx², the site of treatment also contained a donor population of cells. In each case, an NGF-containing polymer was implanted adjacent to (≈1–2 mm) or separate (≈3 mm) from the site of treatment. (b) Concentration of NGF as a function of distance from the implant site: the polymer pellets were identical except for the rate of NGF release, which was moderate (≈0.1 mg/day; circles) or high (≈1,00 mg/day; squares; data replotted from ref. 30). The most likely therapeutic window for NGF is between the minimum effective (0.1 ng) and maximum tolerated (100 ng) tissue concentration. (c) Effect of NGF positioning on a treatment site that contained a native-cell population (circles, n = 4) or native and donor cells (triangles, n = 4). Levels of ChAT activity were significantly elevated above that of controls when NGF-containing polymers were implanted local to the site of treatment. Control animals received blank polymers. Error bars indicate SEM. ChAT activity was elevated significantly at ≈1 mm (P < 0.01) for both experimental conditions.