Blood and Brain Caen Normandie Institute

Junior Professor Chair, ANR 2023-2026

Project coordinator:

Dr. Igor Khalin, INSERM U1237, Blood and Brain Caen Normandie Institute, Caen, France.

After ischemic stroke the cerebral microcirculation may not re-perfuse even when large vessels have been recanalized leading to a poor recovery of the stroke patients. In was shown in clinic, that low cerebral blood flow (CBF) immediately after re-canalization highly correlates with poor outcome and higher lesion volume a day after (Zhou et al., Stroke, 2022). One of the possible causes of low CBF is microthrombosis, which mechanism and consequences, however, are not well understood. We recently developed super-bright nanoparticles, which are non-toxic and superior in brightness compared to conventional quantum dots (Reisch et al., 2014). We optimized several biocompatible nano-compounds to in vivo and ex vivo imaging modalities in normal and diseased mouse brain distinguishing single particles in several brain compartments as well as extravasation into the brain (Khalin et al., 2020, 2022a, 2022b).
Using super-bright lipid-nanodroplets (LNDs) after brain injury in mice we showed that nanoparticles have the ability to efficiently accumulate inside microthrombi within the cerebral microcirculation which opened possibility for new approaches in imaging as well as potentially in drug-delivery (Khalin et al., 2022). First of all, this enabled us to discover an intricate link between microthrombi and blood-brain barrier (BBB) leakage, and to track it through fluorescent microscopy both ex vivo and in vivo (Khalin et al., 2020, 2022, 2024).
Since LNDs can not only be loaded with fluorescent molecules but also with pharmacologically active substances, next to a novel labelling technique in fact it was also developed novel drug carriers which can be used to target blood clots. Provided it will be possible to uncover the mechanisms underlying the pathogenesis of spontaneous microthrombosis after stroke, these LNDs could be used to prevent clot formation or to dissolve already formed MT.