Inflammation in Traumatic Brain Injury: Roles for Toxic A1 Astrocytes and Microglial–Astrocytic Crosstalk

Traumatic brain injurytriggers neuroinflammationthat may contribute to progressive neurodegeneration. We investigated patterns of recruitment of astrocytesand microglia to inflammation after brain trauma by firstly characterising expression profiles over time of marker genesfollowing TBI, and secondly by monitoring glial morphologies reflecting inflammatory responses in a rat model of traumatic brain injury(i.e. the lateral fluid percussioninjury). Gene expression profiles revealed early elevation of expression of astrocyticmarker glial fibrillary acidic proteinrelative to microglial marker allograft inflammatory factor 1(also known as ionized calcium-binding adapter molecule 1). Adult rat brains collected at day 7 after injury were processed for immunohistochemistry with allograft inflammatory factor 1, glial fibrillary acidic proteinand complement C3 (marker of bad/disruptive astrocyticA1 phenotype). Astrocytespositive for glial fibrillary acidic proteinand complement C3 were significant increased in the injured cortex and displayed more complex patterns of arbourisation with significantly increased bifurcations. Our observations suggested that traumatic brain injurychanged the phenotype of microglia from a ramified appearance with long, thin, highly branched processesto a swollen amoeboid shape in the injured cortex. These findings suggest differential glial activation with astrocyteslikely undergoing strategic changes in morphology and function. Whilst a detailed analysis is needed of temporal patterns of glial activation, ours is the first evidence of a role for the bad/disruptive astrocyticA1 phenotype in an open head model of traumatic brain injury.