Microdialysis is widely used in animal models and human patients to monitor and assess the extracellular neurochemistry of the living, intact brain. It has made significant contributions to the study of the neurochemistry of behavior, CNS pathology, drug discovery, and clinical care. Despite its many beneficial attributes, microdialysis suffers from an overlooked drawback in that implanting the probes causes a penetration injury to the tissues being analyzed. The penetration injury results in opening of the blood brain barrier, ischemia of the tissue surrounding the probe, and the activation of astrocytes that eventually engulf the probe track in a glial scar. The penetration injury affects the outcome of microdialysis experiments, i.e. the results reflect the neurochemical attributes of the injured, rather than normal, tissues. The goal of the research proposed here is to establish the feasibility of ameliorating the penetration injury and its impact on microdialysis results by the combined use of a powerful anti-inflammatory drug, dexamethasone, and a novel mitochondrially-targeted electron and radical scavenging cytoprotective agent. The outcome of this research will have a lasting and significant impact on the several branches of neuroscience that involve the insertion of devices into brain tissues, including microdialysis, electrochemical sensors, and neuroprosthetic devices such as deep brain stimulators and neuron recordings arrays.

Public Health Relevance

Microdialysis is highly relevant to public health as a tool used to investigate the role of brain chemistry in behavior, CNS disease, drug discovery, and clinical care. Although the technique has many beneficial attributes, it is also true that the probes damage and disturb the brain tissue that is analyzed. Ameliorating this damage and isruption will improve the use of microdialysis by increasing the physiological relevance of the results it provides.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS081744-01A1
Application #
8540509
Study Section
Special Emphasis Panel (ZRG1-ETTN-G (02))
Program Officer
Hicks, Ramona R
Project Start
2013-05-01
Project End
2015-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
1
Fiscal Year
2013
Total Cost
$228,750
Indirect Cost
$78,750
Name
University of Pittsburgh
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213