• Bullock, Ross (PI)
  • Patterson, John (PI)
  • Kontos, Hermes (PI)
  • Jenkins, Lawrence (PI)
  • Choi, Sung (PI)
  • Lutz, Harry A. (PI)
  • Hayes, Ronald L. (PI)
  • Ellis, Earl (PI)
  • Ward, John D. (PI)
  • Sgro, Joseph A. (PI)
  • Becker, Donald (PI)
  • Hamm, Robert J. (PI)
  • Muizelaar, J. Paul (PI)
  • Lyeth, Bruce (PI)
  • Povlishock, John T. (PI)
  • Phillips, Linda L. (PI)
  • Marmarou, Anthony (PI)
  • Young, Harold (PI)

Project: Research project

Project Details


This competitive renewal seeks continued support for a program project
which, over its history, has made a dedicated effort to better understand
the complex pathobiology of human traumatic brain injury (TBI) and, based
upon such understanding, develop more rational therapeutic strategies.
The theme of this application centers on the role of receptor-mediated
neuronal injury and its relation to the release of excessive excitatory
neurotransmitters. In the laboratory, this application moves on the
premise that an initial, excessive release of excitatory
neurotransmitters, elicited by the TBI, causes receptor-mediated injury,
leading to neuronal dysfunction and/or death. In this vane, one
laboratory effort assesses the damaging consequences of increased
neurotransmitter release in TBI to determine if transmitter-related
neurotoxicity can be amplified by synergetic mechanisms. Another
laboratory project examines the consequences of this excessive
transmitter release in terms of excessive receptor activation to elicit
the altered coupling of the neurotransmitter receptors to their effector
molecules. Another laboratory component examines the role of these
abnormal receptor-mediated interactions by examining their long-term
consequences in terms of cognitive dysfunction. Lastly, in the lab, the
concept of receptor-mediated change will be considered not only in the
context of generalized neuroexcitation but also in the context of diffuse
injury, complicated by focal insult/deafferentation. In the clinical
setting, efforts will be made to better document the role of excitatory
neurotransmitters in the pathobiology of TBI. Intracerebral
microdialysis will be employed in patients to measure local excitatory
amino acid levels as well as ionic flux and lactate/pyruvate ratios in
varied brain regions. These microdialysis studies will be conducted in
concert with studies of CBF and ICP changes. These CBF changes will be
provided as an extension of another project which will examine the
genesis of the altered early ischemia seen after TBI. Lastly, in this
same patient population, studies will be performed to better elucidate
the mechanisms responsible for the brain swelling and subsequent ICP rise
seen after brain injury. Efforts will be made to determine if brain
edema is derived primarily from cellular swelling due to either ischemic
or neurotoxic processes. Collectively, we believe that all of the above
projects are logical outgrowths of our previous research efforts. They
explore important issues directly relevant to the pathobiology of human
TBI and most likely will suggest new therapeutic approaches for the more
rational treatment of human TBI.
Effective start/end date4/1/798/31/06


  • National Institutes of Health: $1,291,587.00
  • National Institutes of Health: $1,448,020.00
  • National Institutes of Health: $154,935.00
  • National Institutes of Health: $1,522,222.00
  • National Institutes of Health: $1,492,018.00
  • National Institutes of Health: $6,660.00
  • National Institutes of Health: $1,260,320.00


  • Medicine(all)
  • Neuroscience(all)


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