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Numerous clinical trials of thrombolytic and neuroprotective drugs for stroke have been conducted over the last 2 decades. The NINDS trial of intravenous tissue plasminogen activator remains the most notable success. Intra-arterial thrombolysis appears promising, but in the absence of phase III clinical trial data, this approach remains investigational. Numerous pharmaceutical drugs targeting 1 or more cell death pathways have failed to show efficacy. Despite failure, these prior attempts have provided insights regarding critical issues such as proper clinical trial design and the need for more rigorous preclinical drug testing in order to improve the translational leap from bench to bedside.More recently, accumulating data suggest that “non-drug” approaches toward stroke therapy might also provide new opportunities in addition to more traditional pharmaceutical therapies. As testimony to the growing importance of these alternate and sometimes complementary methods, there has been a proliferation of device trials, and the NINDS, through its key ‘Specialized Program of Translational Research in Acute Stroke’ [SPOTRIAS] initiative,1 has funded trials of therapeutic hypothermia, caffeinol, and normobaric hyperoxia, among others. Although this brief survey focuses on emerging gas and device therapies for ischemic stroke, it should be noted that several other ‘non-drug’ approaches, including physiological strategies (eg, hypothermia, glucose regulation), and natural agents (eg, albumin, magnesium), continue to be tested in ongoing trials.Increasing brain tissue oxygenation has long been considered a logical stroke treatment strategy. Although initial efforts using hyperbaric oxygen (HBO) chambers were unsuccessful, the realization that early trials had numerous methodological shortcomings has led to a resurgence of interest in hyperoxia.2 As a potential treatment, oxygen has distinct advantages over pharmaceutical drugs: it easily diffuses across the blood-brain barrier to reach target tissues, may act via multiple pathways, and high concentrations of oxygen in brain might be well tolerated.In the past …

Advances in Emerging Nondrug Therapies for Acute Stroke 2007