Grant: Project Grant

We have discovered that many people with MS have low oxygen levels in the brain (hypoxia). We have also found brain hypoxia in the mouse EAE model, the most commonly used animal model of central nervous system inflammation. This supports the idea that both inflammation and hypoxia responses are linked in a cycle, where inflammation causes hypoxia and hypoxia stimulates inflammation. This grant proposal will use the EAE model and novel imaging tools that are only available in my lab to determine if inflammation can cause hypoxia, and whether that hypoxia can make MS worse. We can quantify hypoxia using unique implantable oxygen probes, which we helped design, MRI and NIRS. Hypoxia could be caused by inflammation, resulting in blockage of small vessels and reduction in local oxygen delivery. We will look for this with histology. The inflammation and the loss of myelin covering the axons could cause an increase in metabolic rate. With MRI, we can measure blood flow and assess myelin loss, and with a unique light based system (near-infrared spectroscopy or NIRS) we can quantify metabolic rate. Since the imaging methods have potential for translation to patients, this aspect of the proposal will demonstrate how MRI and NIRS might be used to monitor hypoxia in humans. After determining whether there is a correlation between hypoxia, brain damage and loss of function, we will further study the link by blocking either inflammation or increasing oxygen in parallel studies. We already know that there is inflammation in MS, but only recently did we discover that there is hypoxia. This project will be the only one in Canada to have our unique mouse NIRS system and the ability to combine this with MRI to study the link between hypoxia and inflammation. We will create new knowledge on how inflammation and hypoxia interrelate, and provide new evidence on how oxygen therapy can be helpful in a condition of inflammation induced hypoxia.