There is evidence that low-energy infrared laser irradiation (LELI) can modify a number of disease states,and in preclinical and clinical studies we have developed preliminary data showing that stroke is among them.Since intravenous tissue plasminogen activator (tPA) is currently the only FDA-approved treatment for acutestroke, but increases the absolute rates of resolution of symptoms only from 25% to 38%, there is need foradditional therapeutic modalities to further contain or eliminate brain damage. We have developed a series ofanimal cerebral ischemia and hemorrhage models that, when used in a coordinated fashion, should helpidentify many of the important variables in LELI that pertain to its viability, safety, and efficacy as an adjunctivetherapy to thrombolysis. Toward this end, this project is designed to achieve the following specific aims: (1)Examine the interaction of LELI with tPA therapy using a rabbit small clot brain embolism model (SCEM),which allows monitoring of a behavioral endpoint. This approach should yield information that helps to predictthe clinical outcome of LELI combined with tPA in humans. The study also examines whether there is anyeffect of LELI on tPA-induced intracerebral hemorrhaging in the large clot embolism model (LCEM), which willserve to warn or reassure clinical investigators about the potential of LELI side effects in stroke victims. (2)Conduct a phase II clinical trial to test safety and preliminarily assess efficacy of LELI in combination with tPAwith acute stroke patients.One approach to stroke therapy, in addition to thrombolysis, is to provide some form of neuroprotectionimmediately after stroke onset to reduce the damage caused by lack of blood flow and increase the window ofopportunity for thrombolytic therapy. A second strategy is to administer neuroprotection after initiation ofthrombolysis to reduce damage while thrombolysis is occurring. A third is to induce neuroprotection afterthrombolysis is complete to salvage tissue that would otherwise die even though blood flow has been restored.Finally, it would be useful to develop strategies to produce recovery of function that may restore at least someneurological function. LELI is potentially capable of producing all of these effects. The potential impact of thestudy results on acute stroke therapeutics is thus far-reaching.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
2P50NS044148-06
Application #
7505981
Study Section
Special Emphasis Panel (ZNS1-SRB-G (21))
Project Start
2008-07-01
Project End
2013-04-30
Budget Start
2008-07-01
Budget End
2009-04-30
Support Year
6
Fiscal Year
2008
Total Cost
$114,800
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Spokoyny, Ilana; Raman, Rema; Ernstrom, Karin et al. (2015) Defining mild stroke: outcomes analysis of treated and untreated mild stroke patients. J Stroke Cerebrovasc Dis 24:1276-81
Spokoyny, Ilana; Raman, Rema; Ernstrom, Karin et al. (2015) Accuracy of First Recorded ""Last Known Normal"" Times of Stroke Code Patients. J Stroke Cerebrovasc Dis 24:2467-73
Coffman, Clarity R; Raman, Rema; Ernstrom, Karin et al. (2015) The ""DeyeCOM Sign"": Predictive Value in Acute Stroke Code Evaluations. J Stroke Cerebrovasc Dis 24:1299-304
Lyden, Patrick D; Hemmen, Thomas M; Grotta, James et al. (2014) Endovascular therapeutic hypothermia for acute ischemic stroke: ICTuS 2/3 protocol. Int J Stroke 9:117-25
Spokoyny, Ilana; Raman, Rema; Ernstrom, Karin et al. (2014) Imaging negative stroke: diagnoses and outcomes in intravenous tissue plasminogen activator-treated patients. J Stroke Cerebrovasc Dis 23:1046-50

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