In the United States, stroke is the third leading cause of death and the leading cause of disability. Despite the success of recent clinical trials of antithrombotic drugs for the secondary prevention of stroke, annually about 10% of patients with recent cerebrovascular accidents have recurrent strokes. The development of new treatment strategies for the secondary prevention of stroke is an important issue for modern medicine. There is increasing evidence that inflammation at the sites of endothelial activation plays an important role in the pathogenesis of stroke. Control of molecular inflammation at the sites of endothelial activation can be achieved by induction of mucosal tolerance. The induction of mucosal tolerance with repeated, low-dose, intranasal administration of antigen causes a shift of immune response from proinflammatory T(H)1 type to anti-inflammatory T(H)2 type at the sites of inflammation. E-selectin is an adhesion molecule expressed only on activated endothelium in response to proinflammatory cytokines. The major goal of proposed study is to test whether repeated administration of low-dose, intranasal E-selectin can induce mucosal tolerance to this compound causing a shift of immune response from T(H)1 to T(H)2 type in patients with recent stroke or TIA, and secondly to evaluate the safety and tolerability of this strategy for the secondary prevention of stroke.
INCLUSION CRITERIA: Patients with recent (greater than 30 and less than 120 days) stroke or TIA over the age of 45 years are eligible for the current study. Patients must be on at least one antithrombotic medication (coumadin, aspirin, ticlopidine, clopidogrel, aspirin+dypyridamole). Patients are allowed to be on cholesterol lowering (simvastatin, pravastatin, atrovastatin), antihypertensive (beta blockers, ACE inhibitors, Ca+ channel blockers, diuretics), antidiabetic, and non-steroidal anti-inflammatory medication. Patients treated with t-PA in an acute phase of stroke are eligible for the trial. Males and females of childbearing potential must be on an adequate form of birth control. All patients will have (or have recently had) brain (CT or MRI), neurovascular (ultrasound or MRA), and cardiac (transthoracic echocardiography) imaging, as well as EKG, fasting blood surgar, lipid profile, serum homocysteine and coagulogram. EXCLUSION CRITERIA: Age less than 45 years. Intracranial or extracranial dissection, Moya Moya disease, vasculitis, radiation-induced vasculopathy, fibromuscular displasia, venous thrombosis. Immunosuppressive medication including: prednisone, cyclophosphmide, cyclosporine, methotrexate, azathioprine, mycophenolate mofetil, anti-CD3 moab (Othoclone OKT3), takrolimus (FK506), sirolimus, anti-IL2r moab (simulect, zenapax), thymoglobulin, thalidomide. Known autoimmune diseases (RA, LE, MS, Myasthenia Gravis, etc,). Cancer and lymphoproliferative diseases. Thrombocytopenia (platelets less than 100,000). HIV and other known immunodeficiencies. Recent major surgery (within one month). Systemic infections, or severe focal infections. Alcohol or substance abuse. Dementia or psychiatric problems (determined by examination, mini-mental status test and consent interview) that prevent the patient from providing informed consent or following an outpatient program reliably. A severe neurological deficit that renders the patient incapable of living independently. Pregnancy. Chronic rhinopathy. Chronic sinusitis.