Potential Role of Neuroprotective Agents in the Treatment of Patients with Acute Ischemic Stroke.

Abstract

Currently, intravenous recombinant tissue plasminogen activator is the only US Food and Drug Administration-approved therapy for acute ischemic stroke. Although efficacious, its usefulness is limited, mainly because of the very limited time window for its administration. Neuroprotective treatments are therapies that block the cellular, biochemical, and metabolic elaboration of injury during or after exposure to ischemia, and have a potential role in ameliorating brain injury in patients with acute ischemic stroke. More than 50 neuroprotective agents have reached randomized human clinical trials in focal ischemic stroke, but none has been unequivocally proven efficacious, despite successful preceding animal studies. The failed neuroprotective trials of the past have greatly increased understanding of the fundamental biology of ischemic brain injury and have laid a strong foundation for future advance. Moreover, the recent favorable results of human clinical trials of hypothermia in human cardiac arrest and global brain ischemia have validated the general concept of neuroprotection for ischemic brain injury. Recent innovations in strategies of preclinical drug development and clinical trial design that rectify past defects hold great promise for neuroprotective investigation, including novel approaches to accelerating time to initiation of experimental treatment, use of outcome measures sensitive to treatment effects, and trial testing of combination therapies rather than single agents alone. Although no neuroprotective agent is of proven benefit for focal ischemic stroke, several currently available interventions have shown promising results in preliminary trials and may be considered for cautious, off-label use in acute stroke, including hypothermia, magnesium sulfate, citicoline, albumin, and erythropoietin. Overall, the prospects for safe and effective neuroprotective therapies to improve stroke outcome remain promising.