While the proven success and corresponding uptake of mechanical thrombectomy for the treatment of acute ischaemic stroke has undoubtedly changed the face of stroke care forever, attention is now being placed on the implications these treatments could have on blood vessels in the brain. Hence the increasing research that is currently ongoing into methods of neuroprotection.
NeuroNews speaks to William Mack (Keck School of Medicine, University of Southern California, Los Angeles, USA), one of the foremost researchers into neuroprotective therapies, about current research, how neuroprotectants work and the potential for the future.
Why is there a need for neuroprotectants? What evidence has brought about this need?
We, as a field, have become very good at opening blood vessels in the brain in the setting of stroke. This gives patients the best chance at a good functional outcome following large vessel stroke. This is done by administering “clot-busting medication” called tPA and through mechanical thrombectomy procedures. However, there are still many patients who present too late to receive these treatments or who have clinical characteristics that exclude them from treatment. Brain tissue may be further preserved before, during, and after the blood vessel opening by administration of neuroprotective therapies. Further, neuroprotective strategies may be applicable to patients who are not eligible for pharmacological or mechanical revascularisation.
How do neuroprotectants work? What is the aim of using them?
Different neuroprotective agents work through different mechanisms. They work, at the molecular level, to preserve brain tissue in the setting of cerebral ischaemia. The aim of using them is to save brain tissue that has a decreased supply of oxygen. The use of neuroprotective agents may ultimately allow for a longer time window, or safer administration, of the medications and procedures that we currently use to open blood vessels in the setting of stroke.
What are the different types of neuroprotectants and how do they work?
Neuroprotective agents work through a wide range of mechanisms on a host of targets. They act on the neurons and supporting cells of the brain, in addition to the blood-brain barrier that protects the cells of the brain. Some examples include targeted hypothermia, anti-inflammatory agents, and vasodilators. It is believed that the neuroprotective agents that will be most successful will likely act through multiple mechanisms on a variety of targets (cell types).
When is the ideal time that neuroprotectants should be used?
As time is critical in the setting of stroke, the sooner the better. Currently, neuroprotective agents are being administered by paramedics in the ambulance on the way to the hospital (by a large research team in Los Angeles, USA). These agents can be administered through intravenous access in the hospital or through catheters directly into the arteries during mechanical thrombectomy procedures.
What is your research with neuroprotectants currently focused on?
My research on neuroprotection currently examines anti-inflammatory strategies with a particular focus on the complement cascade.
What do you think the future holds in terms of the treatment of stroke patients?
I think the future is bright for stroke treatment. The combination of neuroprotection and revascularisation is especially promising. Harnessing neuroprotective agents (such as 3K3A-APC) that affect multiple targets (cell types) through varying mechanisms will likely have the highest chance of success in treating patients with acute large vessel stroke.
What are the STAIR criteria, and why are they useful?
The STAIR (Stroke Treatment Academic Industry Roundtable) recommendations are a set of criteria for basic science research that are believed to help in translating successful findings in animal research to human stroke therapies. Despite success in animal studies, no neuroprotective strategies have proven beneficial in the setting of focal stroke in humans. The idea behind the STAIR recommendations is to increase the chance of success in translating therapies to clinical medicine. These criteria highlight the importance of performing preclinical stroke research in animals of varying age and gender along with those with pertinent medical comorbidities (among other suggestions). This type of variability helps to better approximate the situations encountered in treating acute stroke patients.