Cell surface glycocalyx control of immune cell recruitment and pathology in the inflamed brain

There is exquisite control of immune cell recruitment to all bodily tissues. In injury and disease, such control is important to appropriately resolve the insult or infection whilst limiting inflammation that can drive pathology. In the brain, this takes on critical significance, as central nervous system neurons do not regenerate, therefore limiting damage by infiltrating inflammatory immune cells is crucial to retain function. Chemokines are molecules that mediate immune cell recruitment, and are heavily implicated in pathological brain inflammation, but have not been successfully therapeutically targeted during inflammation due to limited understanding of their basic biology. My lab has produced published and preliminary data demonstrating that an under-appreciated structure, the glycocalyx, on endothelial- and immune- cells regulates chemokine mediated immune cell recruitment by: 1\. Physically regulating the interaction between endothelial and immune cells, that is required for recruitment into the inflamed brain. 2\. Containing proteoglycans that can directly act as chemokine receptors to drive immune cell recruitment during pathological neuroinflammation. This proposal will transform our understanding of how the glycocalyx regulates cell trafficking to the inflamed brain, using stroke as a model condition, which is the second leading cause of disability and death worldwide, but lacks treatment options.