Biography

Biography: Audrey Lafrenaye

Abstract

Mild traumatic brain injury (mTBI) is a highly prevalent disease with devastating costs. While one of the major pathological hallmarks of TBI is diffuse axonal injury (DAI), neuroinflammation occurring chronically, weeks to months following injury, has also been implicated in a variety of detrimental as well as regenerative functions. Currently, little is known regarding acute neuroinflammation occurring within the first day following mTBI, particularly within the gyrencephalic brain. Therefore, we assessed acute neuroinflammation at 6h and 1d in a unique model of diffuse mTBI in the micro pig. Mild TBI did not precipitate systemic physiological abnormalities or overt histopathological damage; however, this micropig model generated substantial DAI in the thalamus, an area commonly affected in human mTBI, at both 6h and 1d following injury. Extensive acute neuroinflammation was also observed following mTBI within the thalamic domain. Importantly, the processes of activated microglia converged on axons sustaining DAI at both time points following mTBI. Contacts between activated microglia processes and swellings of injured axons increased two fold at 6h and nearly fourfold at 1d following mTBI compared to associations with uninjured myelinated axons in sham animals. While active phagocytosis was observed in association with wallerian degeneration following mTBI, the microglia that contacted swellings from diffusely injured axons were not ultra-structurally phagocytic. This study shows direct physical correlation between injured axonal swellings and non-phagocytic acute neuroinflammation in a higher order animal, finding that could lead to novel diagnostics based on a more complete understanding of acute neuroinflammation following mTBI.