A Combined Treatment with Taurine and Intra-arterial Thrombolysis in an Embolic Model of Stroke in Rats: Increased Neuroprotective Efficacy and Extended Therapeutic Time Window

Combination treatment may target different pathophysiological events following cerebral ischemia thus enhancing the efficacy of treatment in thromboembolic stroke. Taurine confers a neuroprotective effect in the mechanical stroke model. This effect has not been assessed in an embolic stroke model. Here, we sought to evaluate the neuroprotective effect of taurine alone and in combination with thrombolytic therapy to investigate whether combined administration would extend the therapeutic time window without increasing the hemorrhagic transformation in a rat embolic stroke model. Rats were subjected to right embolic middle cerebral artery occlusion and then randomly assigned to the following groups: saline treatment alone at 4 h, urokinase, taurine treatment alone at 4, 6, or 8 h, and the combination of taurine and urokinase at 4, 6, or 8 h after the insult. Brain infarct volume, neurobehavioral outcome, regional cerebral blood flow, intracranial hemorrhage incidence were observed and evaluated. Posttreatment with taurine at 4 or 6 h, urokinase at 4 h or in combination at 4, 6, or 8 h significantly reduced infarct volume and improved neurobehavioral outcome. The combination treatment had better neurobehavioral outcome and smaller infarction volume than urokinase or taurine treatment alone. The clinical outcome correlated well with infarct volume. Together, the present study suggests that administration of taurine after stroke is neuroprotective, seemingly because it reduces the reperfusion damage of urokinase, leading to widen the therapeutic window for the thrombolytic effect of urokinase to 8 h. Thrombolysis can also enhance the neuroprotective effect of taurine. The reduction of inflammatory response, neuron death and inhibition of blood brain barrier (BBB) disruption may underlie the beneficial effects of combination of taurine and urokinase in the treatment of embolic stroke.