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Séminaire - Louis-Philippe BernierA role for brain pericytes in cerebrovascular regeneration after stroke

Abstract :

Brain pericytes of the neurovascular unit (NVU) are critical for the developmental maturation of cerebral blood vessels and for the integrity of the blood-brain barrier (BBB). Pericytes are perivascular mural cells that share similarities with mesenchymal progenitors (MP), a cellular pool critical in supporting peripheral tissue regeneration.
Therefore we examined what role brain pericytes play in repairing and restoring the cerebral microvasculature following stroke using a new transgenic MP reporter mouse that specifically identifies brain pericytes. Here we show that after stroke, pericytes enter the cell cycle to support cerebrovascular regeneration in a manner similar to their role during development. Following stroke, pericytes proliferate and migrate into the infarct region where they accumulate inside a border of reactive astrocytes.
 The pericyte-astrocyte interface forms an angiogenic zone that progressively migrates into the ischemic core, thereby supporting a wave of tissue revascularization.  Within a few weeks normal vessels with an intact BBB are found perfusing the previously ischemic cortical area. Using single-cell and population RNA sequencing, we identify transcriptional signatures of naïve pericyte subpopulations as well as a functional and transcriptional profile of activated pericytes following trauma.
Brain pericytes in the adult brain represent a ¬major progenitor population that can modify their phenotype to contribute to the regeneration of cerebral blood vessels following injury in a process that recapitulates their role in developmental vasculogenesis.

Selected publications

Microglial modulation of neuronal activity in the healthy brain. York EM, Bernier LP, MacVicar BA.
Dev Neurobiol. 2017 Dec 22. doi: 10.1002/dneu.22571. [Epub ahead of print] Review. PMID: 29271125

P2X receptor channels in chronic pain pathways. Bernier LP, Ase AR, Séguéla P. Br J Pharmacol. 2017 Jul 20. doi: 10.1111/bph.13957. [Epub ahead of print] Review.

The cost of communication in the brain.MacVicar BA, Wicki-Stordeur L, Bernier LP. Elife. 2017 May 22;6. pii: e27894. doi: 10.7554/eLife.27894.PMID: 28534473

Inhibition of P2X4 function by P2Y6 UDP receptors in microglia. Bernier LP, Ase AR, Boué-Grabot É, Séguéla P. Glia. 2013 Dec;61(12):2038-49. doi: 10.1002/glia.22574. Epub 2013 Oct 7.

Scientific focus :

I investigate multiple aspects of stroke pathophysiology, with a focus on the involvement of two different cell types, pericytes and microglia. Pericytes are part of the neurovascular unit, and we demonstrate that they represent a major pool of mesenchymal progenitor cells in the brain that are critically involved in repair processes. Using in vivo and ex vivo two-photon imaging, optical coherence tomography and single cell RNA sequencing approaches, we show that after stroke, pericytes proliferate, migrate and modify their functional profile to promote angiogenesis and regeneration of the cerebrovascular unit. This work describing a novel and critical role for pericytes is currently under review and would form the major part of my talk.

Studying microglia, the immune cells of the brain, we have shown that upon decreases in oxygen levels, microglia rapidly adapt their morphology and functional phenotype and do so by sensing environmental acidosis that accompanies anoxia. Another project describes how microglia use actin-rich filopodia to contact neighboring cells and allow them to sense or survey the brain parenchyma. A third aspect of my microglia work shows that microglia have a remarkably plastic cellular metabolic signature, in that they can rapidly alter their intracellular metabolic use depending on the availability of energy sources