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Project Title:
Adenosine and Traumatic Brain Injury
Funding Agency:
NIH/Neurological Institute
Total Project Period:
Aug 01, 1999 - Jul 31, 2008
Principal Investigator:
Patrick Kochanek, MD
Co-Investigator(s):
C Edward Dixon, Larry Jenkins, Edwin Jackson, Stephen Wisniewski, Xaiopeng
Zhang
Project Summary:
Adenosine is a purine nucleotide that acts as a powerful endogenous neuroprotectant during ischemia-induced energy failure by decreasing neuronal metabolism and increasing cerebral blood flow (CBF), among other mechanisms. Two strategies to achieve this are particularly relevant to TBI and this application, namely, 1) the inhibition of adenosine metabolism or 2) the local administration of adenosine analogs. Defining four specific aims, we will use an established rat model of TBI and applying cerebral microdialysis, contemporary MRI tools, functional outcome testing, and histology, we will first determine the magnitude of the adenosine response (brain interstitial levels of adenosine and purine degradation products) to experimental TBI.
We will then examine effects of augmenting adenosine effects both on key mechanisms of secondary damage and both functional and histopathological outcome. Finally, we will bridge bench to bedside by using cerebral micro dialysis methods to define the participation of adenosine after severe TBI in
humans. If successful, these studies will set the stage for a clinical trial, and provide important mechanistic information on the role of adenosine after TBI in humans.
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