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 was administered IV following the injection of small
blood clots into the brain vasculature. Behavior was measured 24 h 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 min following embolization significantly (p<0.05) increased P(50) values by 104% and 181%; but not when given 3 h 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 h following embolization. In combination studies, when
TSC was administered 1 h and tPA was given either 1 or 3 h following embolization, the group P(50) values were increased by 291% and 140%, respectively. In addition,
TSC plus tPA administered 3 h 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 h 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.