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ARRA Investments in Stroke


Public Health Burden
Stroke is the third leading cause of death and a leading cause of severe long-term disability in the United States. It especially affects the elderly—nearly three-quarters of all strokes occur in people over the age of 65 and the risk of having a stroke more than doubles each decade after the age of 55.

Treatment
NIH clinical trials identified the clot-busting drug “tPA” as an effective treatment for stroke, significantly reducing the likelihood of disability when given within three hours of stroke onset. However, tPA only works for ischemic and not hemorrhagic stroke, it is not recommended for everyone, and its effectiveness has not been clearly established for patients who arrive to the hospital beyond the three hour time window. A variety of ARRA funded grants are exploring new treatments for acute stroke and ways to extend the stroke treatment window for tPA.
  • Scientists are validating whether rapid automated brain imaging analysis can be used to identify patients who may benefit from tPA treatment 3 to 6 hours after stroke onset. 1,2
  • Used in combination with tPA, the anticoagulant Argatroban may improve outcomes after a stroke. A Phase II trial will evaluate the safety of the combination treatment. If the results are positive, this study will provide preliminary evidence for a final Phase III trial.3
  • Researchers are identifying compounds that reduce damage to the blood brain barrier during a stroke and that may expand the therapeutic window for acute stroke treatment. 4
  • A family of small molecule drugs has been shown to protect nerve cells from a variety of insults associated with stroke. An ARRA award is optimizing the potency and specificity of the compounds and testing them in animal models of the disease.5
  • A research group is determining whether an inhaled gas, ethyl nitrite, improves blood flow during experimental stroke in rats and whether it reduces the amount of tissue damage and neurologic impairment caused by a stroke. This could be an adjunct therapy during or after tPA treatment.6
  • There are few treatment options for hemorrhagic stroke. Scientists are developing a minimally invasive tool for evacuation of intracerebral blood or blood clots that is easy to use and suitable for the ICU. 7
Stroke Risk Factors and Prevention
Hypertension, diabetes, and smoking have been identified as risk factors for stroke. Stroke survivors have an increased risk of a recurring stroke. Economic studies have estimated that if strokes could be prevented it would have great cost saving effects. ARRA awards are using genetic analysis techniques to identify additional risk factors for stroke and exploring ways to prevent first-ever and recurring stroke.
  • Brain imaging and clinical data are being used in a Challenge Grant to define risk factors of aneurysm rupture and the effectiveness of surgical procedures in preventing hemorrhage. 8
  • One study has recruited members of Dominican families with a predisposition for stroke to identify genes associated with markers of stroke risk such as plaque in the artery that supplies the brain. Identifying these genes may help us understand and prevent the development of stroke.9
  • Vascular malformations or aneurysms can rupture causing hemorrhagic stroke, the deadliest form of stroke. Prevention of hemorrhagic stroke will be advanced through an ARRA award identifying genes variants that are associated with the formation and rupture of aneurysms.10
  • A Phase III clinical trial is examining whether clopidogrel, a drug that prevents platelet aggregation and clot formation, is effective in reducing the risk of stroke after an initial transient ischemic attack or mini-stroke.11
Rehabilitation
Stroke survivors are often left with residual motor or cognitive impairment. Physical and behavioral rehabilitation can be used to improve function after a stroke. A number of ARRA awards are illuminating the mechanisms that underlie functional recovery and are helping to optimize rehabilitation protocols, thereby reducing the social and economic burden of stroke.
  • A Challenge Grant is studying how the brain translates movement intentions to commands for muscle activation and how these brain programs change after a stroke. This research may help improve rehabilitation strategies and improve the design of brain-controlled prosthetic devices.12
  • After leaving the hospital, patients may receive post-acute stroke care in a wide-range of settings with varying results. A Challenge Grant will use electronic medical records and a computer assessment of rehabilitation to compare patient outcomes across post-acute care sites.13
  • NIH funds helped develop the AMES device for motor rehabilitation. AMES couples robotic-assisted movement with muscle vibration to enhance movement sensation. An ARRA grant will study the mechanisms of movement sensation to optimize the AMES device.14
  • Cortical brain stimulation has been shown to improve the effects of motor training after a stroke. One grant is using an animal model to understand the cellular changes that promote functional recovery through cortical stimulation, which may lead to optimized therapies.15
  • Another grant is optimizing the parameters of non-invasive brain stimulation to enhance the effects of motor training following a stroke.16



  1. 2R01NS039325-04A2 -- Diffusion weighted imaging Evaluation For Understanding Stroke Evolution 2: DEFUSE -- Albers, Gregory W (CA)
  2. 3K23NS051372-04S1 -- Who Benefits from tPA 3-6 hours after Stroke -- Lansberg, Maarten G (CA)
  3. 3P50NS044227-07S3 -- A pilot Study To Determine the Safety of Argatroban Injection in Combination with rt-PA In Patients With Acute Ischemic Stroke -- Grotta, James C (TX)
  4. 1R21NS066418-01 -- Matrix Metalloproteinase Inhibitors in Stroke -- Rosenberg, Gary Allen (NM)
  5. 1R01NS060864-01A2 -- A Novel Family of Neuroprotective Compounds for Stroke -- Schubert, David R (CA)
  6. 1R21NS063108-01A1 -- S-Nitrosylated Hemoglobin and Ischemic Brain Injury -- Warner, David
  7. 1R21EB008228-01A1 -- Minimally Invasive Navigated Brain Hematoma Evacuation with Ultrasound Monitoring -- Nikou, Constantinos (contact); Oh, Michael Y (PA)
  8. 1RC1NS068092-01 -- Predictors of Long-Term Outcome of Unruptured Intracranial Aneurysms -- Torner, James C (IA)
  9. 2R01NS040807-07 -- Family Study of Stroke Risk and Carotid Atherosclerosis -- Sacco, Ralph L (FL)
  10. 2R01NS039512-06A1 -- Familiar Intracranial Aneurysm Study II -- Broderick, Joseph P (OH)
  11. 1U01NS062835-01A1 -- Platelet-Oriented Inhibition in New TIA -- Johnston, S. Claiborne (Contact), Palesch, Yuko Y (CA)
  12. 1RC1NS068103-01 -- Applying a Multidimensional Algorithm for Motor Control -- Bizzi, Emilio (MA)
  13. 1RC1NS068397-01 -- Kaiser Permanente Functional Outcomes System -- Sandel, M. Elizabeth (CA)
  14. 2R01NS061304-21A2 -- Spatial and temporal control of targeted limb movement -- Cordo, Paul J. (OH)
  15. 1R21NS063332-01A1 -- Cortical Stimulation to Enhance Experience-Dependent Plasticity After Stroke -- Jones, Theresa A
  16. 1R21HD060999-01 -- Transcranial Direct Current Stimulation and Motor Training in Chronic Stroke -- Edwards, Dylan J (NY)


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