Post-docs and students

Details: Emilie Chamma, M.Sc. Student

Co-advisors : Daniel Côté and Yves DeKoninck
Research : In vivo imaging of the blood-brain barrier disruption in a multiple sclerosis animal model.

Multiple sclerosis (MS) is a chronic disease that causes inflammation and demyelination of the central nervous system. The lesions are the result of a high number of immune cells (leukocytes) that crossed the blood-brain barrier to get into the central nervous system (CNS). To develop better therapies, it is essential to understand the early stages of the infiltration, in particular the proteins and molecular events involved. Researchers are now looking at the mechanisms behind the infiltration of leukocytes in the CNS.

The main focus nowadays is towards endothelial cells of the blood-brain barrier (BBB-ECs). The BBB-ECs are responsible for the cytokines and chemokines that regulate immune cell recruitment and infiltration within the CNS in case of inflammation or infection. Inflammatory cytokines and chemokines appear to play a great role in the pathogenesis of MS and its experimental autoimmune encephalomyelitis (EAE) animal model. For instance, they regulate cell adhesion molecules that play an important part in leukocyte transmigration from the blood to the CNS, thus increasing the permeability of the blood-brain barrier (disruption). Demyelination of the axons is seen in mice with EAE and is caused by leukocyte infiltration.

We will use optical and CARS microscopy to image in vivo the blood-brain barrier breakdown and demyelination. To do so, five steps will be taken : i) Use a spinal window for longitudinal imaging of the spinal cord ii) Use markers of blood-brain barrier disruption iii) Use non- specific permeability measurements iv) Use CARS microscopy to quantify demylination iv) Establish a temporal correlation between the blood-brain barrier permeability and demyelination. Our hypothesis is that mice that eventually develop EAE will show increased levels of specific cytokines/chemokines and this will correlate with increased endothelial cell activation, increased blood-brain barrier permeability and increased demyelination. In vivo imaging will enable us to follow the sequence of events over time.