Current and future pharmacological interventions for the acute treatment of ischaemic stroke

Currently there are few effective therapeutic interventions for the acute treatment of ischaemic stroke. The few that do exist are primarily thrombolytics such as recombinant tissue plasminogen activator, which reperfuse the ischaemic brain region but do not otherwise aid in neuroprotection. One of the principal explanations as to why the vast majority of neuroprotective drug trials have failed is that the drugs' therapeutic windows were too narrow to be clinically effective. The inflammatory reaction post-stroke makes a significant contribution to the neurological deterioration witnessed in patients. Since inflammatory mediators have been shown to be upregulated from 1 h to 3 months post-stroke, they represent an ideal target to exploit for therapeutic interventions as their 'actions' can potentially be halted within a clinically relevant therapeutic window. There is also mounting evidence that ischaemic stroke can be exacerbated by a predisposition to chronic inflammation and autoimmunity. This review details the role of inflammation and autoimmunity in stroke and how mediators of these pathways can be developed for therapeutic interventions. Recommendations are also made for an ideal therapy regime for acute ischaemic stroke, utilizing currently available, clinically proven treatments. Lastly, novel strategies for future experimental and clinical stroke research are discussed.