The wide availability, low cost, and multiple biochemical, molecular and hemodynamic effects of? hyperoxia make it ideally suited as a neuroprotective strategy. In animal studies, and in a recent pilot human? study, we have documented that breathing high-flow oxygen (normobaric hyperoxia therapy or NBO) during? brain ischemia confers potent neuroprotection. The benefit of NBO appears to be transient, similar to that? observed in prior hyperbaric oxygen studies. However, sustained benefit does occur if NBO-treated tissue is? reperfused. We believe that today, with enhanced reperfusion rates from newer therapies such as tPA, and? advances in MRI that allow serial assessment of tissue ischemia-reperfusion, there exists an exciting? opportunity to assess whether NBO's transient tissue-salvaging effects can be converted (via induced or? spontaneous reperfusion) into sustained benefit. By preventing early ischemic cell death, NBO may be a? feasible strategy to extend the narrow time window for IV tissue plasminogen activator (tPA) therapy.? In this proposal we aim to extend our preliminary work in a double-blind study enrolling 150 acute (<12? hours) ischemic stroke patients over 5 years. Patients will receive NBO or Room Air for 8 hours and will? undergo serial clinical examinations and diffusion-perfusion MRI (DWI/PWI). Safety and efficacy of NBO will? be determined in an 'intention to treat' statistical analysis of change in NIH stroke scale scores during and? after therapy. The potential synergistic benefit of NBO with reperfusion will be assessed. We will also? compare MRI ischemic lesion growth and hemorrhage rates, and perform novel voxel-based analyses of? DWI and PWI parameters. In year 1 we will exclude tPA-treated patients and investigate the safety of NBO? with tPA in an embolic (clot-based) rodent stroke model. If the combination appears safe in rodents, and if? the year 1 human data raises no safety concerns, we will expand to include tPA-treated patients. Finally, we? will conduct pathological and in-vivo MRI studies in rodent stroke models to investigate whether NBO can? extend the tPA time window, and to investigate NBO's effects on cerebral hemodynamics.? These studies are significant because they will comprehensively test the effects of oxygen in the ischemic? brain. Breathing high-flow oxygen may prove to be a simple, practical, portable, and potentially cost-effective? therapy that improves stroke outcomes, either independently or by extending the time window for IV tPA.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS051412-03
Application #
7490647
Study Section
Clinical Neuroscience and Disease Study Section (CND)
Program Officer
Jacobs, Tom P
Project Start
2006-09-07
Project End
2011-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
3
Fiscal Year
2008
Total Cost
$543,284
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Matsouaka, Roland A; Singhal, Aneesh B; Betensky, Rebecca A (2018) An optimal Wilcoxon-Mann-Whitney test of mortality and a continuous outcome. Stat Methods Med Res 27:2384-2400
Hirai, Kelsi K; Groisser, Benjamin N; Copen, William A et al. (2016) Comparing prognostic strength of acute corticospinal tract injury measured by a new diffusion tensor imaging based template approach versus common approaches. J Neurosci Methods 257:204-13
Lima, Fabricio O; Silva, Gisele S; Furie, Karen L et al. (2016) Field Assessment Stroke Triage for Emergency Destination: A Simple and Accurate Prehospital Scale to Detect Large Vessel Occlusion Strokes. Stroke 47:1997-2002
Battey, Thomas W K; Karki, Mahima; Singhal, Aneesh B et al. (2014) Brain edema predicts outcome after nonlacunar ischemic stroke. Stroke 45:3643-8
Singhal, Aneesh B; Lo, Warren (2014) Life after stroke: Beyond medications. Neurology 83:1128-9
Kimberly, W Taylor; Battey, Thomas W K; Pham, Ly et al. (2014) Glyburide is associated with attenuated vasogenic edema in stroke patients. Neurocrit Care 20:193-201
Groisser, Benjamin N; Copen, William A; Singhal, Aneesh B et al. (2014) Corticospinal tract diffusion abnormalities early after stroke predict motor outcome. Neurorehabil Neural Repair 28:751-60
Ji, Ruijun; Schwamm, Lee H; Pervez, Muhammad A et al. (2013) Ischemic stroke and transient ischemic attack in young adults: risk factors, diagnostic yield, neuroimaging, and thrombolysis. JAMA Neurol 70:51-7
Maas, Matthew B; Singhal, Aneesh B (2013) Unwitnessed stroke: impact of different onset times on eligibility into stroke trials. J Stroke Cerebrovasc Dis 22:241-3
Esposito, Elga; Mandeville, Emiri T; Hayakawa, Kazuhide et al. (2013) Effects of normobaric oxygen on the progression of focal cerebral ischemia in rats. Exp Neurol 249:33-8

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