Intra-arterial neuroprotective therapy as an adjunct to endovascular intervention in acute ischemic stroke: A review of the literature and future directions

Mechanical thrombectomy for acute ischemic stroke due to large vessel occlusion has been shown to significantly improve outcomes. However, despite efficient rates of recanalization (60-90%), the rates of functional independence remain suboptimal (14-58%), most likely due to pathways of cell death in the brain that have already committed despite successful reperfusion. Pharmacologic neuroprotection provides a potential means of preventing this inevitable damage through targeting excitotoxicity, reactive oxygen species, cellular apoptosis, and inflammation. Numerous clinical trials using various neuroprotective agents have failed, but the majority of these trials did not include endovascular reperfusion, and thus the drugs were not reaching the therapeutic target. Intra-arterial delivery of neuroprotective agents via the guide catheter already in place for mechanical thrombectomy could provide a way to deliver high doses directly to the affected territory while limiting systemic exposure. Agents that have shown promise via the intra-arterial route in preclinical as well as some clinical models include magnesium sulfate, verapamil, cold saline, stem cells, and various combined approaches. Targeted hypothermia, achieved with intra-carotid infusion of cold saline, may provide an effective means of achieving hypothermia of the ischemic tissue while avoiding the systemic effects that have limited its use previously. Combination therapy of targeted hypothermia and a cocktail of drugs that provide anti-excitotoxic, anti-oxidant, anti-apopototic, and anti-inflammatory effects may provide an ideal approach that deserves further study in clinical trials.