Combination of thrombolytic therapy and neuroprotective therapy in acute ischemic stroke: is it important?

Tissue plasminogen activator (tPA) is the only treatment approved by the USA FDA for acute ischemic stroke. There are many obstacles, however, when it is widely used in clinical setting, such as narrow therapeutic window, cytotoxicity and neurotoxicity. In recent years, many neuroprotective agents aiming to different molecular targets in ischemic cascade have been rapidly developed. Although these agents showed remarkable effects in experimental stroke, they failed to be translated to clinical use for many reasons. As the concept of "neurovascular unit" (NVU) is mentioned, combination of thrombolytic agents such as tPA with neuroprotectants gets more and more attention. Evidences supporting the combination therapy have been obtained from a variety of studies in many kinds of animal models, even though clinical evidences are inadequate. Combination of thrombolysis and neuroprotection has been considered as a promising approach for treatment of acute ischemic stroke. There are many advantages for the combination therapy. In this context, we review the sound rationales and researching achievements to support the therapy.