Stroke Therapy Development Successes: Research Guidelines and Embolic Stroke Models for Monotherapy and Adjuvant Therapy Development

Acute ischemic stroke patients now have the benefit of receiving either thrombolytic therapy or endovascular procedure therapy, alone or with an approved thrombolytic to significantly improve clinical outcome measured using the modified Rankin scale. Most recent data indicate that large vessel occlusion stroke victims can achieve a modified Rankin scale score of 0–2, clinically normal, 3–12 months after treatment. Like tissue plasminogen activator (rt-PA), endovascular procedures will be of benefit to a small well-defined patient population, because it appears that a small ischemic core and large penumbral substrate are a prerequisite for neuroprotection and functional recovery. Endovascular procedures and thrombolysis both effectively target reperfusion of the penumbra to promote cell survival, but neither therapy actually targets a specific mechanism directly involved in the ischemic cascade, a complex series of temporally regulated events that result in differential death of cellular populations in the brain. With our constantly evolving understanding of cell death mechanisms, we now have the opportunity to develop neuroprotective or cytoprotective strategies to use as adjuvant therapy with endovascular procedures and rt-PA to further promote function and potentially repair ischemia-damaged cellular pathways. The benefit of testing novel neuroprotective and cytoprotective therapies as an adjuvant in the patient population defined above will take advantage of both large penumbra and reperfusion of the penumbra. Progress to develop new therapies will be inextricably linked to standardization of translational research practices, complete transparency of data, and adherence to STAIR, RIGOR, ARRIVE, and VOW guidelines. Moreover, because the target population will be undergoing reperfusion therapies, the recommendation is for translational research to be conducted in standardized and validated embolic stroke models.