Proportion of single-chain recombinant tissue plasminogen activator and outcome after stroke.

OBJECTIVE: To determine whether the ratio single chain (sc)/(sc + 2 chain [tc]) recombinant tissue plasminogen activator (rtPA) influences outcomes in patients with cerebral ischemia. METHODS: We prospectively included consecutive patients treated with IV rtPA for cerebral ischemia in 13 stroke centers and determined the sc/(sc + tc) ratio in the treatment administered to each patient. We evaluated the outcome with the modified Rankin Scale (mRS) at 3 months (prespecified analysis) and occurrence of epileptic seizures (post hoc analysis). We registered Outcome of Patients Treated by IV Rt-PA for Cerebral Ischaemia According to the Ratio Sc-tPA/Tc-tPA (OPHELIE) under ClinicalTrials.gov identifier no. NCT01614080. RESULTS: We recruited 1,004 patients (515 men, median age 75 years, median onset-to-needle time 170 minutes, median NIH Stroke Scale score 10). We found no statistical association between sc/(sc + tc) ratios and handicap (mRS > 1), dependency (mRS > 2), or death at 3 months. Patients with symptomatic intracerebral hemorrhages had lower ratios (median 69% vs 72%, adjusted p = 0.003). The sc/(sc + tc) rtPA ratio did not differ between patients with and without seizures, but patients with early seizures were more likely to have received a sc/(sc + tc) rtPA ratio >80.5% (odds ratio 3.61; 95% confidence interval 1.26-10.34). CONCLUSIONS: The sc/(sc + tc) rtPA ratio does not influence outcomes in patients with cerebral ischemia. The capacity of rtPA to modulate NMDA receptor signaling might be associated with early seizures, but we observed this effect only in patients with a ratio of sc/(sc + tc) rtPA >80.5% in a post hoc analysis.

Biomaterial Applications in Cell-Based Therapy in Experimental Stroke.

Stroke is an important health issue corresponding to the second cause of mortality and first cause of severe disability with no effective treatments after the first hours of onset. Regenerative approaches such as cell therapy provide an increase in endogenous brain structural plasticity but they are not enough to promote a complete recovery. Tissue engineering has recently aroused a major interesting development of biomaterials for use into the central nervous system. Many biomaterials have been engineered based on natural compounds, synthetic compounds, or a mix of both with the aim of providing polymers with specific properties. The mechanical properties of biomaterials can be exquisitely regulated forming polymers with different stiffness, modifiable physical state that polymerizes in situ, or small particles encapsulating cells or growth factors. The choice of biomaterial compounds should be adapted for the different applications, structure target, and delay of administration. Biocompatibilities with embedded cells and with the host tissue and biodegradation rate must be considerate. In this paper, we review the different applications of biomaterials combined with cell therapy in ischemic stroke and we explore specific features such as choice of biomaterial compounds and physical and mechanical properties concerning the recent studies in experimental stroke.