Editorial [Hot Topic: Therapeutic Approaches in the Treatment of Stroke (Guest Editor: Kevin Pong)]

Stroke is the third leading cause of death and the leading cause of long-term disability in the United States: 25 % of sufferers die from a stroke or its complications and 50 % have health problems and long-term disabilities following a stroke. Additionally, stroke is one of the most costly diseases, with estimated annual healthcare expenditures exceeding $40 billion in the United States alone. Approximately 80 % of strokes are ischemic in nature, caused by a transient or permanent reduction in cerebral blood flow. This reduction in blood flow is typically caused by either an embolic or thrombotic blockade of a blood vessel. A narrowing of a blood vessel can also cause an ischemic stroke. The remaining 20 % of strokes are hemorrhagic in nature, caused by rupture of a blood vessel and resulting plasma leakage into the brain. Despite decades of research and the large number of compounds that have been shown to reduce ischemic damage in preclinical animals models, clinical trials with many of these compounds have yielded disappointing results. To date, the only FDAapproved treatment for acute ischemic stroke is tissue plasminogen activator (tPA), which restores blood flow by dissolving clots. However, its efficacy and utility are limited by its short therapeutic window and potentially devastating side effects, in particular the possibility of inducing intracerebral hemorrhage. The review articles in this hot topic issue of Current Drug Targets-CNS and Neurological Disorders highlight a gamut of neuroprotective therapeutic agents and strategies that are in various stages of development for stroke. Green and Ashwood review free radical trapping as a therapeutic approach to neuroprotection in stroke, concentrating on experimental and clinical studies with Cerovive (NXY-059) and other free radical scavengers. Next, Lutsep summarizes the neuroprotective effects of serotonin agonists in pre-clinical models of stroke and early clinical data for Repinotan (BAY x 3702). Ren and Finklestein discuss the potential utility of select growth factors as treatments for stroke and clinical data for two of these factors, bFGF and EPO. Asano and colleagues focus on the calcium binding protein S100B and the effects of arundic acid (ONO-2506) in preclinical stroke studies. Wang and Shuaib discuss the utility of NR2B selective NMDA receptor antagonists while Weiser discusses AMPA receptor antagonists for the treatment of stroke, since glutamate toxicity remains a hallmark of stroke. The pro-inflammatory agent tumor necrosis factor-α (TNF- α) has been shown to be involved in the neuropathology following stroke. Lovering and Zhang review the therapeutic potential of tumor necrosis factor-alpha-converting enzyme (TACE, which generates soluble, mature TNF- α) inhibitors in stroke. Yang and colleagues summarize the evidence supporting estrogens as protective agents against stroke. Finally, Komjati and colleagues focus on poly (ADP-ribose) polymerase inhibitors as potential therapeutic agents in treating stroke and neurotrauma. Taken together, these reviews provide an overview of the diverse approaches being employed to tackle acute ischemic stroke: they are a testament to the unmet medical needs of stroke patients, and also to the complexity of the major pathogenic mechanisms believed to be important in this disease.