Neuronal, glial, immune and vascular cells work in concert to enable critical neurovascular interactions that include cerebral blood flow (CBF) regulation, blood-brain barrier (BBB) maintenance, angiogenesis, vascular stabilization, neurogenesis, neuronal plasticity, and immune modulation. Deregulation of the neurovascular interactions in cerebrovascular diseases and vascular dementia (VaD) affects tissue damage and repair. Unfortunately, there is still a major gap in the therapeutic options for these neurological conditions. Most research efforts in the field during the last decades emphasized on rescuing neuronal survival per se. Unfortunately, such a simplistic approach does not translate complexity of the pathophysiological processes. We are convinced that in order to achieve major breakthroughs in the field, it is primordial to adopt a holistic approach integrating the continuum of events that profoundly shape neurovascular interactions under pathological conditions.
The research program integrates cutting-edge molecular, cellular and imaging approaches to investigate how endothelial cells, pericytes, glial cells, monocytes crosstalk affect neuronal function in vascular-mediated brain pathologies. These goals are achieved using transgenic mice that allow tracking cells of interest or modulating their function in vivo, while modelling brain pathologies, including stroke, cerebral small vascular disease (cSVD), and Alzheimer’s disease (AD). Our research strategy consists on identifying and targeting specialized mechanisms that could restore overall neurovascular functions as a gateway for brain repair and regeneration.
In order to efficiently develop the research program, a wide array of experimental techniques are regularly used, including microsurgery in mice, inducible Cre-Lox recombination in mice, Tet-on gene expression system in mice, perivascular reporter mice, chimeric mice generation, fluorescent microscope combined to optical sectioning via structured illumination (Apotome.2), laser scan confocal microscope, laser Doppler flow measurements, laser Speckle contrast imaging, primary cell cultures, ischemic-like condition in vitro, cell reprogramming (viral and non-viral), non-invasive brain cell transplantation, and live cell imaging. These techniques are applied in conjunction with immunohistological analysis, biochemical and molecular techniques (WB, ELISA, RT-QPCR, siRNA, shRNA), and multiplex fluorescent in situ hybridization (FISH). Furthermore, the lab benefits from additional specialized technical approaches available through either strategic national and international collaborations or specialized platforms at our institution, such as 2-photon intravital microscope, super-resolution microscopes (2P-STED, SPT-PALM, SLAM), cytometry platform equipped with conventional systems and a cutting-edge CyTOF system, as well as genomic (RNAseq, single cell RNAseq), proteomic and bioinformatic platforms.