Abstract
Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in children, especially toddlers (~2-3 years old). Despite pediatric TBI’s prevalence, its underlying progression of cellular outcomes are largely extrapolated from adult studies. Notably, axonal injury and acute microglial activation following pediatric TBI remains under-characterized. We addressed this gap by utilizing a central fluid percussion injury (cFPI) model in postnatal day 16-18 male and female rats to investigate axonal injury burden, microglia morphological and Iba-1 fluorescence intensity changes acutely following sham or cFPI in the lateral cortex (CTX), subcortical white matter (SCWM) and thalamus (THAL). Microscopic assessment revealed diffuse axonal injury within the CTX, SCWM, and THAL with different temporal progressions that largely resolved within 1d post-injury. Microglial morphology changed significantly 1h post-injury in the CTX and THAL and 3h post-cFPI in the SCWM. Interestingly, microglial changes generally preceded peak axonal injury burden. These findings demonstrate rapid, region-specific, and temporally distinct microglia activation following diffuse TBI. Additionally, utilizing high-dimensional morphological profiling can define microglia responses in the developing brain, potentially revealing novel therapeutic windows for pediatric TBI intervention.