The overall goal of this Program Project is to investigate the pathophysiological changes that occur during injury and treatment in human subjects with acute brain damage. We will investigate three types of acute brain injury: intracerebral hemorrhage, ischemic stroke and head trauma. In Project 1, Dr. Allyson Zazutia will investigate the mechanism, extent and clinical importance of edema following intracerebral hemorrhage. In Project 2, Drs. William Powers and Venkatesh Aiyagari will use PET to determine the effect of pharmacologic reduction of systemic arterial pressure on regional cerebral blood flow in acute ischemic stroke. In Project 3, Drs. Michael Diringer and Robert Grubb will investigate the pathophysiological effects of mannitol and hypertonic saline on brain edema due to ischemic stroke and head trauma. The Imaging Core will perform acquisition, reconstruction, processing and archiving of the PET, MR and CT data for Projects 1,2 and 3 as well as validate recently developed MR methods of CBF and OEF estimation against gold-standard techniques. The Radiochemistry Core will provide radiopharmaceuticals for Projects 1,2 and 3 as well as construct a steady state oxygen-15 gas inhalation system to permit PET studies in subjects who are not endotracheally intubated or who cannot actively inhale. This Program Project draws on a combination of facilities and expertise at Washington University that is unique. It combines state-of-the art quantitative neuroimaging, expertise in the care of critically ill neurological patients and many years experience in studying cerebral blood flow and metabolism. This research will provide fundamentally important pathophysiological information to guide future research toward the most fruitful approaches for ameliorating the devastating impact of acute brain injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS035966-10
Application #
7273714
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Jacobs, Tom P
Project Start
1997-09-01
Project End
2011-05-31
Budget Start
2007-06-01
Budget End
2011-05-31
Support Year
10
Fiscal Year
2007
Total Cost
$1,009,110
Indirect Cost
Name
Washington University
Department
Neurology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Dhar, Rajat; Zazulia, Allyson R; Derdeyn, Colin P et al. (2017) RBC Transfusion Improves Cerebral Oxygen Delivery in Subarachnoid Hemorrhage. Crit Care Med 45:653-659
Dhar, Rajat; Diringer, Michael N (2015) Relationship between angiographic vasospasm, cerebral blood flow, and cerebral infarction after subarachnoid hemorrhage. Acta Neurochir Suppl 120:161-5
Diringer, Michael N (2013) New trends in hyperosmolar therapy? Curr Opin Crit Care 19:77-82
Delgado Almandoz, Josser E; Jagadeesan, Bharathi D; Refai, Daniel et al. (2012) Diagnostic yield of computed tomography angiography and magnetic resonance angiography in patients with catheter angiography-negative subarachnoid hemorrhage. J Neurosurg 117:309-15
Dhar, Rajat; Scalfani, Michael T; Blackburn, Spiros et al. (2012) Relationship between angiographic vasospasm and regional hypoperfusion in aneurysmal subarachnoid hemorrhage. Stroke 43:1788-94
Dhar, Rajat; Scalfani, Michael T; Zazulia, Allyson R et al. (2012) Comparison of induced hypertension, fluid bolus, and blood transfusion to augment cerebral oxygen delivery after subarachnoid hemorrhage. J Neurosurg 116:648-56
Diringer, Michael N; Scalfani, Michael T; Zazulia, Allyson R et al. (2012) Effect of mannitol on cerebral blood volume in patients with head injury. Neurosurgery 70:1215-8; discussion 1219
Dhar, Rajat; Diringer, Michael (2012) Statins and anti-inflammatory therapies for subarachnoid hemorrhage. Curr Treat Options Neurol 14:164-74
Shah, Manish N; Botros, James A; Pilgram, Thomas K et al. (2012) Borden-Shucart Type I dural arteriovenous fistulas: clinical course including risk of conversion to higher-grade fistulas. J Neurosurg 117:539-45
Scalfani, Michael T; Dhar, Rajat; Zazulia, Allyson R et al. (2012) Effect of osmotic agents on regional cerebral blood flow in traumatic brain injury. J Crit Care 27:526.e7-12

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