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- WSC TV - Live Session - Pre-Recorded Session with Live Q&A - On Demand Session (watch anytime) - Session with Voting
Intra-arterial therapy Development in Stroke Pig Models
We are witnessing an enormous impact of endovascular clot removal on outcomes of eligible patients with stroke. This procedure restores blood flow and provides an opportunity for drug delivery to the infarcted area to improve outcomes further. It is particularly compelling to merge mechanical thrombectomy (MT) with intra-arterial drug infusion as a one-stop-shop procedure. Additionally, there is a rapid growth of thrombectomy-capable centers, which may allow to readily use of an intra-arterial route to deliver drugs at a large scale also to MT-ineligible patients, which suffer from a scarcity of therapeutic options. Therefore, there is an urgent need for a highly clinically relevant model capable of restoring blood flow to the infarcted brain to study the therapeutic effect of a variety of potential therapeutic agents. Lisencephalic rodent brains with a low white to gray matter ratio are relatively poor predictors of clinical translations. On the other side, primate and canine stroke models are poorly accessible, prohibitively expensive, and ethically questionable. The pig is the most extensively used large animal in biomedical research. Still, it was not possible to create a porcine model of stroke permitting restoration of blood blow – an condicio sine qua non to recapitulate the current clinical setting due to the rete between extracerebral and intracerebral circulation. We have demonstrated that intra-arterial infusion of thrombin produces a stroke through clot formation, which can be readily dissolved to restore blood flow. Then, we have shown the utility of this model in testing the therapeutic effects of glycolic acid.
Future Applications of Molecular Imaging
The Potential Therapeutic Applications of Microvessicles
Emerging Concepts from Basic Science
The study of the pathophysiological processes of stroke has shed light on numerous mechanisms that could potentially be targeted in order to protect and cure the damaged brain after stroke. However, all the promising neuroprotective drugs from such experimental studies have failed when translated to clinical trials. In this presentation, we will discuss immune mechanisms that may contribute to the translational failure for neuroprotection, specifically related to the function of neutrophils.
Neutrophil infiltration is one of the earliest processes in the stroke ischaemic cascade. After vessel occlusion, neutrophils recruited to the stroke area will worsen cerebral damage via increasing inflammation and oxidative stress, blood-brain damage, and immunothrombosis. But neutrophil function can also be important to ensure appropriate healing, scar formation, and repair. In particular, novel cellular beneficial functions have been ascribed to an unexpected heterogeneity of these cells.
In this context, it has been described that neutrophils released from the bone marrow undergo a natural phenotypic shift in the circulation called “neutrophil aging” that critically affects their immune function, by affecting their capacities of migration, integrin activation, ROS production, and NET formation. Aging may be driven by external cues such as TLR agonists derived from the microbiota, but also by circadian signals dictated by an internal clock.
In the talk, we will discuss how the circadian biology of neutrophils may affect stroke outcome and how a better knowledge of neutrophil heterogeneity may contribute to overcoming the translational roadblock in stroke research.