Understanding the role of the perivascular space in cerebral small vessel disease

European Coordinator:
  • Joanna WARDLAW, University of Edinburgh (UK)
North American Coordinator:
  • Berislav ZLOKOVIC, University of Southern California, Los Angeles (USA)
  • Hélène BENVENISTE, Stony Brook University, NY (USA)
  • Sandra BLACK, SunnyBrook Health Sciences Centre, Toronto, ON (Canada)
  • Serge CHARPAK, Université Paris Descartes, Paris (France)
  • Anne JOUTEL, Institute of Psychiatry and Neurosciences of Paris, Paris (France)
  • Maiken NEDERGAARD, University of Copenhagen (Denmark)
  • Kenneth SMITH, University College London (UK)

Cerebral small vessel disease (SVD) is increasingly acknowledged to contribute to almost half of dementias. There is currently no effective treatment. MRIs done on patients with SVD show specific anatomical structural changes involving the perivascular space, the significance of which is not yet understood. This consortium will pursue the novel hypothesis that cognitive impairment from SVD–associated brain injury is related to these structural changes in the perivascular space. The model of perivascular space based pathology involves thickening of the vessel wall, the presence of inflammatory infiltrates, stagnation of perivascular glymphatic fluid, compromise of the blood-brain barrier, and silent infarction. Exploiting several advanced laboratory and imaging techniques to quantify and characterise changes in perivascular morphology, network members will study short term effects of vascular challenges on the perivascular space in humans, and longer term effects in both well-phenotype humans populations and animal models. Ultimately the project aims to produce insights into non-Mendelian SVD, and eventually therapeutic targets, that would allow for a rational approach to therapy for what is not an intractable condition.