Reliable performance of neural recording electrodes continues to be a very significant hurdle in successful clinical application of neuroprosthetics. Although progressive astrocytic encapsulation and neuronal loss/degeneration have been implicated as principal mechanisms of neuroelectrode failure, recent work has found evidence that persistent inflammation and neurovascular (BBB) compromise may have a more significant role than previously understood. Supplementing animal models, we propose to use a novel microfabricated device that recapitulates essential functions of the "neurovascular unit," enabling the study of tissue response in a controlled fashion and the role of neuroinflammation after probe implantation. Our concept features a neural parenchyma (3-D mixture of neurons, astrocytes, and microglia) in communication with microvascular endothelial cells exposed to flow. In preliminary work we have successfully fabricated test devices, characterized barrier properties, and neuroglial-vascular communication within the device.
The first aim will quantitatively assess the tissue reaction to two different probes and validate the model response using known in vivo data. In the second aim, we will provide proof-of-principle and preliminary insights on the dynamic interplay of neuroinflammation and glial encapsulation, using circulating monocytes and anti- inflammatories. Our long term objective is to develop an automated instrument for mechanistic understanding and screening of novel probe designs, with general applicability towards other CNS disorders.

Public Health Relevance

The ultimate goal of this project is to develop a biomimetic model of a brain on a chip to facilitate better understanding of neurological disease processes and for the rational development of therapeutics and interventional devices. A particular focus is to develop a model that can shed light on the problem of unreliable recording from microelectrodes implanted in the brain- a problem that is not well understood but commonly attributed to tissue reaction. Insights emerging from this study can lead to the development of novel probes that are robust and enable successful clinical use of neuroprostheses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS077285-02
Application #
8679017
Study Section
Special Emphasis Panel (BNVT)
Program Officer
Ludwig, Kip A
Project Start
2013-06-15
Project End
2015-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
$218,594
Indirect Cost
$94,844
Name
Charles Stark Draper Laboratory
Department
Type
DUNS #
066587478
City
Cambridge
State
MA
Country
United States
Zip Code
02139