Meningeal fibroblasts and brain wound healing

Stroke and trauma are the leading causes of brain damage in Australia. Although many people survive the initial event, they are left with devastating neurological impairment that impacts their quality of life. Wound healing is critical to functional recovery from brain damage. In recent years a novel participant in brain damage has come to light, brain fibroblasts. The presence of fibroblasts in the brain was only discovered in 2018, but recent work shows that they vigorously expand after brain damage to form a fibrotic scar. Little is known about the triggers of scar formation, nor how it impacts immunological processes that are critical to tissue repair. We will identify unique wound healing states in meningeal fibroblasts, using novel genetic tools to capture fibroblasts during wound healing after stroke and traumatic brain injury, and comparing these to fibroblasts during wound healing in other organs. We will leverage these data to perform spatial transcriptomics to examine how they interact with immune cells and what drives their proliferation and activation. Finally, we will perform targeted genetic manipulation to specifically disrupt fibroblast immune interactions during wound healing and examine their functional consequences during recovery.