This application is based on preliminary findings that pial arterioles in newborn pigs constrict and cerebral blood flow and metabolism are decreased after fluid percussion injury in brain. The overall hypothesis is that opioids contribute to this reduction in cerebral blood flow and possibly to secondary cerebral ischemia in this model. To examine this hypothesis, three specific aims are planned using newborn and juvenile piglets: 1) to characterize the relationship between local periarachnoid concentrations of opioids, cerebral hemodynamics, and oxygenation following fluid injury, 2) to determine the functional significance of the relationship between brain opioids, brain oxygenation and the cerebral circulation following fluid injury, and 3) to investigate the mechanisms by which endogenous opioids affect cerebral vascular responses subsequent to fluid percussion injury. Vascular responses in these experiments will be measured using radioactive microspheres and a closed cranial window preparation. Local levels of opioids and prostanoids in cerebrospinal fluid will be measured using radioimmunoassay. An index of cerebral oxygenation will be obtained using near infrared spectroscopy. These studies will explore mechanisms involved in regulation of cerebral blood flow in a brain injury model in newborn pigs and should provide new information in an area where few data are available. The investigators suggest that experimental findings may have clinical relevance for mechanisms of head injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034932-03
Application #
2460637
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Program Officer
Cheung, Mary Ellen
Project Start
1995-08-15
Project End
2000-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Armstead, William M; Kreipke, Christian W (2011) Endothelin-1 is upregulated after traumatic brain injury: a cross-species, cross-model analysis. Neurol Res 33:133-6