The foundation of an acute stroke research program is an acute stroke clinical service that will assure maximum patient referral and allow rapid identification, screening and recruitment of potential research subjects in the timely fashion needed to study the early events in cerebral ischemia and enroll patients in acute stroke research protocols. Absence of an emergency department and the time constraints on screening and recruitment of acute stroke patients as research subjects has precluded the NIH Clinical Center as the main site of our research projects. Thus, we have needed to establish and maintain the clinical, imaging and research infrastructure required to support such a program at local hospitals, Suburban Hospital (SH) in Bethesda, Maryland, and Washington Hospital Center (WHC) in DC. The major elements of this infrastructure include the NIH Stroke Service, a combination of NIH and contractor clinicians stroke neurologists, nurses, clinical fellows, on-site research/nurse coordinators, MRI scanners NIH 3T MRI at WHC, shared 1,5 T scanner at SH and MRI technologists, NIH computer network placed and maintained at each hospital, hospital office space for program needs. In addition, we maintain our own PACS for images obtained on the WHC and SH MRI scanners, and developed and maintain a database for clinical and research patient data. In FY2007 we screened approximately 1200 patients and enrolled 248 in one of our research protocols at our two clinical research sites.? ? On the NIH campus, we provide experimental stroke models at the NMR center to support our clinical research efforts. For example, in the past year we developed an experimental model of symptomatic intracranial hemorrhage in ischemic reperfusion using multimodal MRI. Symptomatic hemorrhagic transformation is the most important complicating factor following treatment of ischemic stroke with thrombolytics. Space occupying hemorrhage with mass effect (Type 2 parenchymal hematoma) is the hemorrhage type associated with the most severe adverse clinical effects. After 30 minutes of suture occlusion followed by reperfusion 46% of experimental animals developed parenchymal hematoma (15% Type 2). This model will be used to test novel therapeutics targeting blood-brain barrier integrity and the reduction of intracerebral hemorrhages and the leading candidates will be brought to clinical trial.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS003044-01
Application #
7594735
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2007
Total Cost
$4,114,867
Indirect Cost
City
State
Country
United States
Zip Code
Barr, Taura L; Latour, Lawrence L; Lee, Kyung-Yul et al. (2010) Blood-brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9. Stroke 41:e123-8
Batra, Ayush; Latour, Lawrence L; Ruetzler, Christl A et al. (2010) Increased plasma and tissue MMP levels are associated with BCSFB and BBB disruption evident on post-contrast FLAIR after experimental stroke. J Cereb Blood Flow Metab 30:1188-99
An, Li; Zhang, Yan; Thomasson, David M et al. (2009) Measurement of glutathione in normal volunteers and stroke patients at 3T using J-difference spectroscopy with minimized subtraction errors. J Magn Reson Imaging 30:263-70
Henning, Erica C; Latour, Lawrence L; Warach, Steven (2008) Verification of enhancement of the CSF space, not parenchyma, in acute stroke patients with early blood-brain barrier disruption. J Cereb Blood Flow Metab 28:882-6
Henning, Erica C; Latour, Lawrence L; Hallenbeck, John M et al. (2008) Reperfusion-Associated Hemorrhagic Transformation in SHR Rats. Evidence of Symptomatic Parenchymal Hematoma. Stroke :
Gaudinski, Martin R; Henning, Erica C; Miracle, Aaron et al. (2008) Establishing final infarct volume: stroke lesion evolution past 30 days is insignificant. Stroke 39:2765-8
Kidwell, Chelsea S; Latour, Larry; Saver, Jeffrey L et al. (2008) Thrombolytic toxicity: blood brain barrier disruption in human ischemic stroke. Cerebrovasc Dis 25:338-43
Burgess, Richard E; Warach, Steven; Schaewe, Timothy J et al. (2008) Development and validation of a simple conversion model for comparison of intracerebral hemorrhage volumes measured on CT and gradient recalled echo MRI. Stroke 39:2017-20
Merino, Jose G; Latour, Lawrence L; An, Li et al. (2008) Reperfusion half-life: a novel pharmacodynamic measure of thrombolytic activity. Stroke 39:2148-50
Luby, M; Warach, S (2007) Reliability of MR perfusion-weighted and diffusion-weighted imaging mismatch measurement methods. AJNR Am J Neuroradiol 28:1674-8

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