Abstract Body

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.