Traumatic brain injury (TBI) leads to significant public health concerns due to cognitive decline and increased risks of neurological conditions like Alzheimer’s disease and chronic traumatic encephalopathy. Preclinical models are essential for exploring how mild TBI leads to neuronal dysfunction and neurodegeneration. Using a mouse model, we applied repetitive, mild, side-alternating impacts to induce rapid head rotational acceleration–deceleration. A novel odor-based learning and memory task was developed to address TBI-related vision impairments. Our findings revealed that this side-impact model specifically affects the hippocampus, evidenced by activated CD68+ microglia appearing in the dentate gyrus, stratum lacunosum-moleculare, and corpus callosum. Importantly, no olfactory dysfunction was observed. However, injured mice exhibited learning and memory deficits in an olfaction-based task. These results suggest that repetitive mild TBI damages hippocampal regions, leading to cognitive dysfunction characterized by impaired learning and memory, as demonstrated by this novel behavioral method.
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