Promoting Self-Healing After Stroke

When an ischemic stroke occurs, blood flow is cut off to parts of the brain. Self-healing mechanisms, such as reorganization of the brain exist and are initiated immediately. The researchers behind the UZH Clinical Research Priority Program (CRPP) Stroke want to find out how these plastic processes can be enhanced. ZNZ News talked to Prof. Susanne Wegener, co-head of the CRPP, about the importance of this research and the unique opportunities she sees in the collaborative network of the CRPP.

What are the main goals of the CRPP stroke?
Many stroke survivors show a poor functional recovery, despite significant progress that has been made in acute recanalization therapies, e.g. dissolving or removing of blood clots. Part of the problem is that the circulation of blood in the smallest blood vessels, the so-called microcirculation is failing. This results in only partial reperfusion of the brain. At the same time, surviving tissue surrounding the infarct is able to adapt and compensate for the loss of neurons – a process referred to as neuroplasticity. Our hypothesis is that neuroplasticity depends on effective microcirculation, and that the interaction of vascular and neuronal repair processes is crucial for recovery. In our CRPP, we are using an experimental as well as a clinical approach. In the clinical trial, we exploit novel imaging methods to find out if augmenting large artery flow improves microcirculation and readouts of plasticity. We are using imaging predictors of microcirculatory failure to compose a new decision algorithm for flow-augmentation bypass surgery. Furthermore, we apply state-of-the-art neurorehabilitation and transcranial magnetic stimulation technologies to enhance and measure plasticity and functional recovery.

What was the reason for the initiative to start the CRPP stroke?
Stroke is a frequent and devastating disease. Treatment decisions have to be fast and individualized, since they are associated with side effects. This interdisciplinary CRPP, headed by Prof. Andreas Luft and myself, is possible through a close collaboration within the Clinical Neuroscience Center Zurich between the departments of neurology, neuroradiology, neurosurgery and neuropathology. Within our collaborative network, imaging and electrophysiological modalities to study microcirculation, cerebrovascular reactivity (CVR) and plasticity after stroke have already been established in joint projects. This is a very exciting opportunity and unique in Switzerland.

What does the timeline of the CRPP look like on a high level?
The clinical observational trial started in 2019, and the recruitment process is ongoing. A novel decision algorithm for bypass surgery was recently developed based on advanced imaging technologies. First interim analyses are expected soon. The mid-term goal is to test these new algorithms in a prospective randomized trial for their potential to improve post-stroke recovery. In an in vivo rodent model of clot occlusion and thrombolysis-induced reperfusion, we found considerable no-reflow due to obstruction of capillaries by neutrophils. We are now testing different approaches to remove capillary stalls in these models, along with the visualization of neuronal tracts using tissue clearing and immunofluorescence methods. Furthermore, we apply electrophysiology to observe changes in peri-infarct plasticity in our models.

What do you hope to achieve within the scope of the CRPP?
Our vision is to improve recovery and quality of life for stroke patients by developing novel treatments targeting both, neuroplasticity and microvascular function.

Find out more about the CRPP Stroke.