Stroke is a devastating medical condition, killing millions of people each year and causing serious injury to many more. Despite advances in treatment, there is still little that can be done to prevent stroke-related brain damage. The concept of neuroprotection is a source of considerable interest in the search for novel therapies that have the potential to preserve brain tissue and improve overall outcome. Key points of intervention have been identified in many of the processes that are the source of damage to the brain after stroke, and numerous treatment strategies designed to exploit them have been developed. In this review, potential targets of neuroprotection in stroke are discussed, as well as the various treatments that have been targeted against them. In addition, a summary of recent progress in clinical trials of neuroprotective agents in stroke is provided. 1. Introduction Stroke is one of the leading causes of death and disability worldwide. Despite decades of research, however, treatment options remain limited. In ischemic stroke, the primary focus of treatment is reperfusion. Currently, the only drug approved for the treatment of ischemic stroke is recombinant tissue plasminogen activator (rtPA, alteplase), which has a limited time window for administration and increases the risk for subsequent hemorrhage. Consequently, only a small percentage of patients receive rtPA treatment [1]. While this treatment is effective in opening up occluded cerebral vessels in some patients and can lead to improved outcomes after ischemic stroke, there are currently no approved treatments for the myriad of damaging pathological processes that persist in the brain long after the acute stage. These include the processes of inflammation, excitotoxicity, oxidative stress, apoptosis, and edema resulting from disruption of the blood-brain barrier [2]. In hemorrhagic stroke, additional processes include physical damage from the mass of accumulated blood itself, cytotoxicity of blood components, and vasospasm in subarachnoid hemorrhage [3, 4]. A considerable amount of research has been invested into the development of novel treatments capable of protecting the brain from damage following stroke, with limited success. Numerous neuroprotective treatments have been identified that show great promise in animal models of stroke. Unfortunately, nearly all have failed to provide protection in human trials. The purpose of this review is to provide an overview of targets for neuroprotection in stroke and examples of current research on potential neuroprotective treatments.
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