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Thrombolysis with tissue plasminogen activator (alteplase, Activase trade mark, rtPA; Genentech Inc) has proven beneficial for acute stroke management, even though only 1 - 2% of stroke patients in the US are treated with the drug [1]. Part of the reason for the under utilisation of alteplase may be the narrow therapeutic window and frequent occurrence of serious side effects, such as increased haemorrhage incidence [2,3]. It is because of these shortcomings, that recent efforts have attempted to identify new thrombolytics that might improve the benefit/risk ratio in treating stroke. Second generation derivatives of alteplase have attempted to counteract the side effects of the drug by increasing fibrin specificity (tenecteplase, TNK-tPA; Genentech Inc) or half-life (lanoteplase, SUN-9216; Genetics Institute Inc.). New recombinant DNA methodology has led to the revival of plasmin or a truncated form of plasmin (microplasmin; ThromboGenics Ltd), a direct-acting thrombolytic with non-thrombolytic related neuroprotective activities, as a therapeutic. Other promising approaches for the treatment of stroke include the development of novel plasminogen activators, such as recombinant desmodus rotundus salivary plasminogen activator (rDSPA) alpha-1 (Schering/Teijin Pharmaceuticals) and a mutant fibrin-activated human plasminogen (BB10153; British Biotech Inc.). These important areas of drug discovery and development will be reviewed.

Curcumin has been investigated in preclinical and translational stroke models because of its pleiotropic 'neuroprotective' activities. Since curcumin has poor blood-brain barrier (BBB) penetration following acute administration, creative medicinal chemistry has been used to modify the parent curcumin molecule, resulting in second generation curcuminoids, which have enhanced BBB penetration, improved pharmacokinetics and interact with multiple viable targets to treat stroke.This review covers epidemiological, preclinical and translational data published between 2002 and 2010.There are two main goals: First, epidemiological data comparing the incidence of stroke in North America to that of India, a country where curcumin is a main-stay of the diet is presented. Second, the pharmacological characteristics of curcuminoids are detailed to determine if they should be further studied in translational stroke models for safety and efficacy prior to initiating clinical trials.Curcumin and curcuminoids are neuroprotective in a variety of preclinical stroke models. The novel multi-target curcuminoid, CNB-001, has a superior safety and pharmacokinetic profile and should be further developed as an acute monotherapy or to be used in conjunction with thrombolytics for acute ischemic stroke.

Since the realization that erythropoietin (EPO) molecules have 'neuroprotective' properties, they have been investigated as treatments for acute ischemic stroke (AIS), but not systematically. The results of the 2009 clinical trial showed that EPO was ineffective as a stroke treatment, and moreover, increased mortality when combined with tissue plasminogen activator. Currently, CEPO, an EPO analog, is entering into a safety, tolerability and pharmacokinetic clinical trial for the treatment of AIS.This review covers translational and clinical studies carried out over the period 1998 - 2010.The primary aim of this article is to review the information available regarding the pharmacological and biological characteristics of EPO molecules. Second, based upon the translational research with EPO molecules in preclinical stroke models, a recommendation is made regarding the continued development of EPO molecules as an option to treat AIS.EPO, CEPO and helix B peptide EPO analogs have significant neuroprotective activity is preclinical stroke models. However, given the detrimental effect of EPO in a recent clinical trial, preclinical safety studies of EPO molecules in embolic stroke models that parallel acute ischemic stroke in humans are warrented.