2062 A Rat Model of Second Impact Syndrome: Evidence of Facial Pain, Neurological Changes, and Tissue Alterations

INTRODUCTION: Traumatic brain injury (TBI) can lead to various clinical manifestations and long-term consequences. Second impact syndrome (SIS) has gained attention due to its acute and chronic symptoms. Post-traumatic headache (PTH) is a common symptom of SIS, and inflammatory mediators have been implicated in secondary brain damage. However, limited information is available regarding behavioral, immunological, and histopathological changes in TBI/SIS. METHODS: Female Wistar rats received one (mild TBI), two (SIS), or no (control) cranial impacts at different time intervals. Facial mechanical sensitivity, neurological, and behavioral assessments were performed at different time points. Inflammatory mediators were measured in plasma samples. Histopathological evaluations in the brain tissue were conducted by H&E stained analysis. Mann-Whitney-U and Kruskal-Wallis tests were employed to compare data. RESULTS: Animal groups receiving one or two impacts exhibited decreased facial mechanical sensitivity compared to control groups. Neurological and behavioral assessments revealed significant impairments in the impact groups compared to the control groups. No differences in the concentrations of IL-6 and TNFα were found between any of the impact groups and the naÏve control group. Groups receiving 2-impacts separated by 14-days experienced a decreased concentration of TNFα (p=0.0221) compared to the sham control group. Also compared to the sham control group, concentrations of IL-6 increased in the groups receiving 2-impacts separated by 24-hours (p=0.0463), 3 days (p=0.0065), and 7-days (p=0.0318). Compared to the naÏve control group, a histopathological inflammatory response was found in the following impact groups: 1-impact (p=0.03165), and 2-impacts separated by 24-hours (p=0.002276), 3-days (p=0.00276), 7-days (p=0.001183) and 14-days (p=0.001183). CONCLUSIONS: The studied analysis contribute to a better understanding of the consequences of TBI/SIS and provide a foundation for further investigations on the mechanisms underlying SIS and potential therapeutic interventions.