Critical Early Thrombolytic and Endovascular Reperfusion Therapy for Acute Ischemic Stroke Victims: a Call for Adjunct Neuroprotection

Abstract

Today, there is an enormous amount of excitement in the field of stroke victim care due to the recent success of MR. CLEAN, SWIFT PRIME, ESCAPE, EXTEND-IA, and REVASCAT endovascular trials. Successful intravenous (IV) recombinant tissue plasminogen activation (rt-PA) clinical trials [i.e.: National Institutes of Neurodegenerative Disease and Stroke (NINDS) stroke trial; Third European Cooperative Acute Stroke Study (ECASSIII) and Third International Stroke study (IST-3)] also need to be emphasized. In the recent endovascular and thrombolytic trials, there is statistically significant improvement using both the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Score (mRS) scale, but neither approach promotes complete recovery in patients enrolled within any particular NIHSS or mRS score tier. Absolute improvement (mRS 0–2 at 90 days) with endovascular therapy is 13.5–31%, whereas thrombolytics alone also significantly improve patient functional independence, but to a lesser degree (NINDS rt-PA trial 13%). This article has 3 main goals: (1) first to emphasize the utility and cost-effectiveness of rt-PA to treat stroke; (2) second to review the recent endovascular trials with respect to efficacy, safety and cost-effectiveness as a stroke treatment; and (3) to further consider and evaluate strategies to develop novel neuroprotective drugs. A thesis will be put forth so that future stroke trials and therapy development can optimally promote recovery so that stroke victims can return to “normal” life.

NADPH oxidase inhibitor improves outcome of mechanical reperfusion by suppressing hemorrhagic transformation

“…Various neuroprotective agents have failed to show benefits without reperfusion. It has not been determined whether neuroprotection can reduce reperfusion injury in the setting of mechanical thrombectomy 8 9. There is a need to develop an animal model of severe HT following reperfusion to evaluate neuroprotection in combination with mechanical thrombectomy.…”

Protecting Oligodendrocytes by Targeting Non-Glutamate Receptors as a New Therapeutic Strategy for Ischemic Stroke

“…Though reperfusion therapeutic strategies such as thrombolysis and mechanical clot removal are statistically and clinically effective in ischemic stroke patients [36], neither approach promotes complete recovery. This is largely due to the delayed presentation and secondary cell injury initiated by recanalization.…”

Translational Stroke Research Opportunities and a Strategy to Develop Effective Cytoprotection

“…And (MR. CLEAN) [7], Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) [8], Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours (REVASCAT) [9], Solitaire With the Intention For Thrombectomy as PRIMary Endovascular Treatment (SWIFT PRIME) Trial [10] and Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA) [11]). The immediate goal of the stroke community is to continue to develop novel forms of cytoprotective therapy to further enhance the benefit of embolectomy and thrombolysis [12][13][14]. By demonstrating additional clinical benefit with a cytoprotective compound in standardized translational stroke models, we may be able to initiate clinical trials in patients undergoing thrombolytic/endovascular procedures [12,15].…”

“…The immediate goal of the stroke community is to continue to develop novel forms of cytoprotective therapy to further enhance the benefit of embolectomy and thrombolysis [12][13][14]. By demonstrating additional clinical benefit with a cytoprotective compound in standardized translational stroke models, we may be able to initiate clinical trials in patients undergoing thrombolytic/endovascular procedures [12,15]. However, the development of neuroprotective compounds has been fraught with problems, in particular, the lack of efficacy in many stroke clinical trials.…”

“…However, the development of neuroprotective compounds has been fraught with problems, in particular, the lack of efficacy in many stroke clinical trials. There are many reasons for this failure, and they have been reviewed in detail elsewhere [12,[16][17][18].…”