Focal, remote-controlled, chronic chemical modulation of brain microstructures
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7254.full.pdf
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1.36 MB
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Checksum (MD5)
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Author(s)
Ramadi, Khalil
Dagdeviren, Canan
Spencer, Kevin C
Joe, Pauline
Cotler, Max Joseph
Rousseau, Erin Byrne
Nunez Lopez, Carlos
Graybiel, Ann M
Langer, Robert S
Cima, Michael J.
Date Issued
July 2018
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Ramadi, Khalil B. et al. “Focal, Remote-Controlled, Chronic Chemical Modulation of Brain Microstructures.” Proceedings of the National Academy of Sciences 115, 28 (June 2018): 7254–7259 © 2018 National Academy of Sciences
Version
Final published version
Abstract
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. Keywords: brain; drug delivery; substantia nigra; neural implant; PET
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Massachusetts Institute of Technology. Media Laboratory
McGovern Institute for Brain Research at MIT
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/PNAS.1804372115
