Abstract: 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 the presence of NETs network in intracranial thrombus extracted during AIS reperfusion procedures. Thrombi are encapsulated by these NETs network, which confer t-PA resistance. In fact, in presence of DNAse 1, t-PA-induced thrombolysisis accelerated, whereas DNAse alone is inefficient. These results suggest that a co-therapy associating t-PA and DNAse 1 may potentialize t-PA 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 DNAse, wherein administration of the combination results in enhanced therapeutic efficacy relative to the administration of t-PA alone.