Secondary prevention of stroke: Pleiotropic effects of optimal oral pharmacotherapy.

Stroke is a major cause of mortality and disability worldwide. During the past three decades, major advances have occurred in secondary prevention, which have demonstrated the broader potential for the prevention of stroke. Risk factors for stroke include previous stroke or transient ischemic attack, hypertension, high blood cholesterol and diabetes. Proven secondary prevention strategies are anti-platelet agents, antihypertensive drugs, statins and glycemic control. In the present review, we evaluated the secondary prevention of stroke in light of clinical studies and discuss new pleiotropic effects beyond the original effects and emerging clinical evidence, with a focus on the effect of optimal oral pharmacotherapy.

Beyond free radical scavenging: Beneficial effects of edaravone (Radicut) in various diseases (Review).

Free radicals play an important role in the pathogenesis of a variety of diseases; thus, they are an attractive target for therapeutic intervention in these diseases. Compounds capable of scavenging free radicals have been developed for this purpose and some, developed for the treatment of cerebral ischemic stroke, have progressed to clinical trials. One such scavenger, edaravone, is used to treat patients within 24 h of stroke. Edaravone, which can diffuse into many disease-affected organs, also shows protective effects in the heart, lung, intestine, liver, pancreas, kidney, bladder and testis. As well as scavenging free radicals, edaravone has anti-apoptotic, anti-necrotic and anti-cytokine effects in various diseases. Here, we critically review the literature on its clinical efficacy and examine whether edaravone should be considered a candidate for worldwide development, focusing on its effects on diseases other than cerebral infarction. Edaravone has been safely used as a free radical scavenger for more than 10 years; we propose that edaravone may offer a novel treatment option for several diseases.

Beyond neurological disease: new targets for edaravone (Review).

Free radicals play major roles in the pathogenesis of tissue damage in many diseases and clinical conditions, and the removal of free radicals may offer a treatment option. Several modulators of free radical scavenger pathways have been developed and some have progressed to clinical trials. One such agent, edaravone, was approved in 2001 in Japan for the treatment of cerebral infarction. It has since been shown that edaravone can diffuse into many organs and, in addition to its effects on hydroxyl radical removal, edaravone modulates inflammatory processes, matrix metalloproteinase levels, nitric oxide production, apoptotic cell death, and necrotic cell death. Edaravone also exerts protective effects in a number of animal models of disease and tissue damage, including models of myocardial, lung, intestinal, liver, pancreatic and renal injury. Together with the proven safety of edaravone following 9 years of use as a modulator of free radical scavenging pathways in neurological disease, these additional effects of edaravone suggest that it may offer a novel treatment for several non-neurological diseases and clinical conditions in humans.

HMGB1 as a therapeutic target in spinal cord injury: A hypothesis for novel therapy development.

Historically, clinical outcomes following spinal cord injury (SCI) have been dismal. Severe SCI leads to devastating neurological deficits, and there is no treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. To address all the issues associated with SCI, a multidisciplinary approach is required, as it is unlikely that a single approach, such as surgical intervention, pharmacotherapy or cellular transplantation, will suffice. High mobility group box 1 (HMGB1) is an inflammatory cytokine. Various studies have shown that HMGB1 plays a critical role in SCI and that inhibition of HMGB1 release may be a novel therapeutic target for SCI and may support spinal cord repair. In addition, HMGB1 has been associated with graft rejection in the early phase. Therefore, HMGB1 may be a promising therapeutic target for SCI transplant patients. We hypothesize that inhibition of HMGB1 release rescues patients with SCI. Taken together, our findings suggest that anti-HMGB1 monoclonal antibodies or short hairpin RNA-mediated HMGB1 could be administered for spinal cord repair in SCI patients.