Background and Purpose-Some studies report that women are less likely to receive IV rt-PA treatment for stroke than men. We undertook a meta-analysis to determine whether a sex disparity existed. Methods-We identified studies that reported sex-specific IV rt-PA treatment rates for acute stroke. Eligible studies included acute stroke admissions from single or multiple hospitals, registries, or administrative databases. Random effects odds ratios (OR) and 95% confidence intervals (CI) were generated to quantify sex differences (females versus males) among all ischemic stroke admissions and among the eligible subgroup who arrived within 3 hours without contraindications. Study design and geographic location were explored as sources of heterogeneity. Results-Eighteen studies were included. Study designs included single hospitals (nϭ5), multiple hospitals (nϭ6), registries (nϭ4), and administrative databases (nϭ3). The summary OR was 0.70 (95% CIϭ0.55 to 0.88) indicating that women had a 30% lower odds of receiving rt-PA treatment than men. However, substantial between-study variability existed. Among 13 hospital-based studies, the summary OR was 0.78 (95% CIϭ0.71 to 0.86) with no significant heterogeneity. Among the 3 administrative studies, the OR was 0.55 (95% CIϭ0.34 to 0.90) but with significant heterogeneity. Among 4 studies that included data on the eligible subgroup, women had a nonsignificant lower odds of treatment (ORϭ0.81, 95% CIϭ0.58 to 1.13). Conclusions-Despite the presence of significant between-study variation, women with acute stroke were consistently less likely to receive thrombolysis treatment compared with men. Further studies to explore the origins of this sex disparity are warranted.

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Background and Purpose An urgent need exists to develop therapies for stroke which have high efficacy, long therapeutic time windows and acceptable toxicity. We undertook preclinical investigations of a novel therapeutic approach involving supplementation with carnosine, an endogenous pleiotropic dipeptide. Methods Efficacy and safety of carnosine treatment was evaluated in rat models of permanent or transient middle cerebral artery occlusion. Mechanistic studies used primary neuronal/astrocytic cultures and ex vivo brain homogenates. Results Intravenous treatment with carnosine exhibited robust cerebroprotection in a dose-dependent manner, with long clinically-relevant therapeutic time windows of 6 h and 9 h in transient and permanent models, respectively. Histological outcomes and functional improvements including motor and sensory deficits were sustained at 14 d post-stroke onset. In safety and tolerability assessments, carnosine did not exhibit any evidence of adverse effects or toxicity. Moreover, histological evaluation of organs, complete blood count, coagulation tests and the serum chemistry did not reveal any abnormalities. In primary neuronal cell cultures and ex vivo brain homogenates, carnosine exhibited robust anti-excitotoxic, antioxidant, and mitochondria protecting activity. Conclusion In both permanent and transient ischemic models, carnosine treatment exhibited significant cerebroprotection against histological and functional damage, with wide therapeutic and clinically relevant time windows. Carnosine was well tolerated and exhibited no toxicity. Mechanistic data show that it influences multiple deleterious processes. Taken together, our data suggest that this endogenous pleiotropic dipeptide is a strong candidate for further development as a stroke treatment.