Focal, remote-controlled, chronic chemical modulation of brain microstructures.

Autor:	Ramadi KB; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.; Harvard-Massachusetts Institute of Technology Health Sciences and Technology Division, Massachusetts Institute of Technology, Cambridge, MA 02139., Dagdeviren C; Media Lab, Massachusetts Institute of Technology, Cambridge, MA 02139., Spencer KC; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.; Department of Materials Science, Massachusetts Institute of Technology, Cambridge, MA 02139., Joe P; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139., Cotler M; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.; Harvard-Massachusetts Institute of Technology Health Sciences and Technology Division, Massachusetts Institute of Technology, Cambridge, MA 02139., Rousseau E; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.; Harvard-Massachusetts Institute of Technology Health Sciences and Technology Division, Massachusetts Institute of Technology, Cambridge, MA 02139., Nunez-Lopez C; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.; Media Lab, Massachusetts Institute of Technology, Cambridge, MA 02139., Graybiel AM; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139.; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139., Langer R; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; rlanger@mit.edu mjcima@mit.edu.; Harvard-Massachusetts Institute of Technology Health Sciences and Technology Division, Massachusetts Institute of Technology, Cambridge, MA 02139.; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139., Cima MJ; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; rlanger@mit.edu mjcima@mit.edu.; Harvard-Massachusetts Institute of Technology Health Sciences and Technology Division, Massachusetts Institute of Technology, Cambridge, MA 02139.; Department of Materials Science, Massachusetts Institute of Technology, Cambridge, MA 02139.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Jul 10; Vol. 115 (28), pp. 7254-7259. Date of Electronic Publication: 2018 Jun 25.
DOI:	10.1073/pnas.1804372115
Abstrakt:	Direct delivery of fluid to brain parenchyma is critical in both research and clinical settings. This is usually accomplished through acutely inserted cannulas. This technique, however, results in backflow and significant dispersion away from the infusion site, offering little spatial or temporal control in delivering fluid. We present an implantable, MRI-compatible, remotely controlled drug delivery system for minimally invasive interfacing with brain microstructures in freely moving animals. We show that infusions through acutely inserted needles target a region more than twofold larger than that of identical infusions through chronically implanted probes due to reflux and backflow. We characterize the dynamics of in vivo infusions using positron emission tomography techniques. Volumes as small as 167 nL of copper-64 and fludeoxyglucose labeled agents are quantified. We further demonstrate the importance of precise drug volume dosing to neural structures to elicit behavioral effects reliably. Selective modulation of the substantia nigra, a critical node in basal ganglia circuitry, via muscimol infusion induces behavioral changes in a volume-dependent manner, even when the total dose remains constant. Chronic device viability is confirmed up to 1-y implantation in rats. This technology could potentially enable precise investigation of neurological disease pathology in preclinical models, and more efficacious treatment in human patients. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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