While we have only included in this review the preclinical studies which specified delayed tPA treatment as >4.5 h post stroke onset, it is noteworthy that some other drugs also attenuated HT and other complications associated with tPA treatment initiated at <4.5 h after stroke (e.g., annexin A2, fingolimod, progesterone, progranulin, uric acid, etc.)in animal models [12,13,14]. This evidence concerns the gene ANXA2 and Stroke.