Activation and differentiation of endogenous neural stem cell progeny in the rat Parkinson animal model.

Abstract

The ability to target biologically active molecules to precise locations in the central nervous system (CNS) is a promising therapeutic treatment. It overcomes many problems encountered by systemic delivery. Among these problems are the inability to penetrate the blood-brain barrier (BBB), global actions, and metabolism by peripheral organs, which may result in undesirable side effects. Although direct administration of biological substances to the brain overcomes these problems, there are certain limitations. These limitations primarily include long-term delivery and limited diffusion. The later may be caused by limited extracellular space, cellular metabolism, substance liability, or“the sink effect,” which results from rapid turnover of the cerebrospinal fluid (CSF). To overcome these problems, scientists have been innovative in coming up with effective delivery systems for both clinical use and basic research. Among delivery systems particularly suited for regenerative medicine are genetically engineered cells, biomaterials, and osmotic pumps. The osmotic pump (Durect, Cupertino, CA, USA) consists of a semipermeable hard outer shell, a compressible inner bag that will contain the biological factor, and a high-osmolarity substance between the two. The diffusion of the interstitial water across the outer shell increases the volume and gradually compresses the inner bag. The result is a continuous infusion of substances prepared at specific concentrations into a localized area of the brain.