Theoretical transport models of high-flow microinfusion into brain tissue have been developed, treating the brain as either a rigid or a deformable elastic medium into which macromolecular solutions are infused at flow rates from 0.1 to 6.0 ~l/min. Previous work has shown that this technique allows slowly degraded macromolecules to access treatment volumes in the range of at least 14 to 27 cu cm. These computations have been extended to describe more reactive molecules, such as neuropeptides and growth factors. Penetration depths and associated treatment volumes based on pharmacodynamic effect have been calculated and shown to be strongly dependent on metabolic rate. Treatment volumes are expected, respectively, to be 2.7 cu cm (1.7 cm dia.) and 0.5 cu cm (0.98 cm dia.) for substances of 1-hr (e.g., a chimeric neuropeptide) and 10-min (e.g., a growth factor) reaction times. Such substances achieve infusion steady-state concentration profiles over 0.5-hr to 3-hr infusions and, unlike unreactive macromolecules, possess sigmoidal profiles that lack a precipitous front. Although the greater reactivity of these agents reduces expected tissue penetration, it does not alter the relative advantage that high-flow microinfusion of these agents provides over competing low-flow or polymer-dissolution methods. In other experimental work, we have confirmed the prediction that the slowly clearing macromolecule albumin is transported spherically outward in grey matter with a moving front profile until it encounters a grey-white boundary.
