Dr Zaben has previously undertaken pre-clinical observations in animal models which highlighted positive steps forward in the development of pharmacological strategies to enhance brain repair after injury. However, key neuroinflammatory processes after injury remain poorly understood, particularly in the human brain. Although animal models have been useful in understanding many processes in TBI, the extent to which TBI animal models replicate the human brain’s response to injury has been questioned rendering them less useful for exploring pharmacological approaches. This fellowship award will facilitate focused research on the use of adult human cortical cells. It will specifically examine if and how the damage-associated molecule, High-Mobility Group Box 1 (HMGB1), impacts stem cells' fate. HMGB1 works via toll receptor subtype 4 (TLR4) and the receptor for advanced glycation end-products (RAGE) to initiate neuroinflammation in many brain pathologies. Dr Zaben will examine the HMGB1-TLR4-RAGE pathway in human cortical inflammation and neuronal regeneration after injury, examining internal nervous system stem cell capacity to repair the injured human brain. This is relevant to the treatment of many neurobehavioral sequelae that survivors of brain injury often suffer including cognitive/memory impairments, psychiatric disorders (depression/psychosis) and neurodegenerative diseases (Chronic Traumatic Encephalopathy & Alzheimer's Disease).