Development and characterization of a murine moderate controlled cortical impact model of traumatic brain injury

Abstract

Traumatic brain injury (TBI) is a leading cause of long-term disability, with complex region-specific consequences that demand precise modeling. This study characterizes the structural, cellular, and functional impact of moderate anterior TBI in mice using a controlled cortical impact (CCI) model. Lesion volumes, quantified using 3D ultrasound, were consistent (2.4-2.7mm3). Histology revealed robust gliosis in perilesional regions with widespread microglial (Iba1) and astrocytic (GFAP) activation, extending bilaterally into the cortex and hippocampus while sparing the amygdala. Behaviorally, mice exhibited significant motor and spatial memory deficits, aligning with sensorimotor and hippocampal injury, while fear-conditioned learning remained intact, consistent with preserved amygdalar function. Together, these findings demonstrate that anterior CCI produces reproducible, regionally selective lesions that drive motor and hippocampal-dependent memory impairments while sparing fear-associated circuitry. Integration of 3D ultrasound with behavioral and histological analyses links lesion topography and neuroinflammation to functional outcomes, enhancing the translational relevance of this model.