An easily administrable drug treatment to increase the recanalization rate associated with intravenously t-Pa would represent a major advance in the acute ischemic stroke (AIS) management. The inventors demonstrate that thrombi are encapsulated by Neutrophil extracellular traps (NETS) network, which confer tPA resistance. In fact, in presence of DNAse I, tPA-induced fibrinolysis is accelerated, whereas DNAse alone is inefficient. These results suggest that a co-therapy associating tPA and DNAse I may potentialize tPA efficacy. Accordingly, the present invention relates to a method of treating an acute ischemic stroke (AIS) in a patient in need thereof comprising administering to the patient a therapeutically effective combination of t-PA and recombinant DNAse, wherein administration of the combination results in enhanced therapeutic efficacy relative to the administration of t-PA alone.