TY - JOUR
T1 - Temporal and spatial control of neural effects following intracerebral microinfusion
AU - Stukel, Jill
AU - Parks, Jason
AU - Caplan, Michael
AU - Helms Tillery, Stephen
N1 - Funding Information:
MRC and JMS are funded by NIH R21 NS-051310 and Arizona Biomedical Research Commission 07-07. SIHT is funded by the Fulton School of Engineering and the Arizona Technology Research Initiative Fund.
PY - 2008/4
Y1 - 2008/4
N2 - 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.
AB - 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.
KW - Convection-enhanced delivery
KW - Mass transport
KW - Mathematical model
KW - Neural inactivation
UR - http://www.scopus.com/inward/record.url?scp=41549162900&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=41549162900&partnerID=8YFLogxK
U2 - 10.1080/10611860801886695
DO - 10.1080/10611860801886695
M3 - Article
C2 - 18365881
AN - SCOPUS:41549162900
SN - 1061-186X
VL - 16
SP - 198
EP - 205
JO - Journal of Drug Targeting
JF - Journal of Drug Targeting
IS - 3
ER -