Efficacy and Safety Profile of the Carotenoid Trans Sodium Crocetinate Administered to Rabbits Following Multiple Infarct Ischemic Strokes: A Combination Therapy Study With Tissue Plasminogen Activator. Brain research [Brain Res] Journal article

Trans sodium crocetinate (TSC) is a synthetic small-molecule antioxidant that has the ability to enhance oxygen diffusion to hypoxic tissue. Because TSC is a promising drug candidate to treat acute ischemic stroke (AIS), we tested the hypothesis that TSC may be neuroprotective following cerebral ischemia using a rabbit small clot embolic stroke model (RSCEM) using clinical rating scores as the endpoint. TSC or saline were administered IV following the injection of small blood clots into the brain vasculature. Behavior was measured 24 hours following embolization in order to calculate the effective stroke dose (P(50)) that produces neurological deficits in 50% of the rabbits. A treatment is considered beneficial if it significantly increases the P(50) compared to control. TSC (0.25 mg/kg) given 5 or 60 minutes following embolization significantly (p<0.05) increased P(50) values by 104 and 181%; but not when given 3 hours post-embolization (48% increase, p>0.05). tPA (3.3 mg/kg) produced a significant increase in P(50) when given 1, but not 3 hours following embolization. In combination studies, when TSC was administered 1 hour and tPA was given either 1 or 3 hours following embolization, the group P(50) values were increased by 291% and 140%, respectively. In addition, TSC plus tPA administered 3 hours following embolization significantly (p<0.05) increased the group P(50) value by 90%. There were no significant effects (p>0.05) of either TSC alone or TSC administered in combination with tPA on intracerebral hemorrhage incidence. This study suggests that TSC may be used for the treatment of AIS either alone or when administered before or concomitant with tPA to improve clinical rating scores with a therapeutic window for TSC therapy up to 3 hours in rabbits. Moreover, it appears that TSC can be administered with tPA, since the combination did not result in any significant change in intracerebral hemorrhage incidence.

Brain research [Brain Res]