Acute ischemic stroke (AIS) is a public health issue because of its poor functional outcome and its increasing incidence in the population. Current treatments are focused on the reperfusion of the occluded artery with IV thrombolysis and endovascular therapy (EVT). However, despite 90% of successful reperfusion, more than 50% of large vessel occlusion (LVO) AIS patients treated with EVT are still severely disabled at 3 months.
Preclinical studies in AIS models have highlighted that an acute inflammation response seems to be highly associated with the overall prognosis. New neuroprotective therapeutic strategies able to reduce the innate immune response after an AIS and prevent brain injuries would represent a promising way to improve patient’s outcomes. Neutrophil extracellular trap (NET) formation (NETosis) and NLRP-3 inflammasome assembly are increasingly considered as two of the most powerful mechanisms triggering inflammation especially in hypoxic setting, and seem to be strongly associated with poor outcomes in AIS preclinical studies. In a previous experimental study, we showed the major role of downstream microvascular thromboinflammation in the pathophysiology of AIS and its deleterious impact on outcomes. Remarkably, however, it remains unknown whether LVO in AIS patients triggers a neutrophil-mediated deleterious response beyond the occlusion site, as was described in animal models of ischemic stroke. The INFLAME study aims to describe and understand with a deep and innovative translational approach, the innate immune response and in particular that of NETosis and NLRP-3 inflammasome assembly after an AIS and its impact on disability. Our hypothesis is that these two inter-related mechanisms exert a dire contribution to acute brain damage and could represent new targets for future neuroprotective therapies. The results of the present project are critical and warranted to support future clinical interventional studies.
Monsieur Jean-Philippe DESILLES (Rothschild Medical Development)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
Rothschild Medical Development Rothschild Medical Development
Help of the ANR 283,743 euros
Beginning and duration of the scientific project: March 2023 - 36 Months