Temporal and spatial control of neural effects following intracerebral microinfusion.
Spatial and temporal control of neural drug delivery is critical for many therapeutic applications and analyses of brain patterns and behavior. Specifically, for localized injections that serve to deliver drug or inactivate an isolated tissue region in order to observe changes in neural activity at that site, excess distribution into surrounding regions may confound analysis or adversely affect healthy tissue. Here, we develop a mass transport model that simulates a short period of initial infusion of inactivating drug, followed by a successive convective wash with artificial cerebrospinal fluid (aCSF), while tracking the regions of tissue that are above a certain threshold concentration of inactivating agent. We analyze the effect of parameters such as effective diffusion coefficient, extracellular volume fraction, and injectate concentration upon spatiotemporal distribution profiles. Further, we observe the effects of following the initial injection with a wash-out period with aCSF upon the breadth of the volume affected by the injectate. These simulations indicate that, by injecting small volumes of drug at low concentrations and following them with an aCSF flush, a well-delineated region of tissue can be altered for a controlled duration.
Stukel
Jill M
JM
Harrington Department of Bioengineering, Arizona State University, Tempe, AZ 85287-9709, USA.
Parks
Jason
J
Caplan
Michael R
MR
Tillery
Stephen I Helms
SI
D001921:Brain / Q000187:drug effects*; D004058:Diffusion; D006801:Humans; D008845:Microinjections; D008962:Models, Theoretical; D010599:Pharmacokinetics