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bioRxiv · 10.1101/2024.12.13.628278

Chronic Behavioral and Seizure Outcomes following Experimental Traumatic Brain Injury and Comorbid Klebsiella pneumoniae Lung Infection in Mice

Rewell, S. S.·Shad, A.·Chen, L.·Chu, E.·Wang, J.·Chen, K.·O'Brien, T. J.·Li, J.·Casillas-Espinosa, P. M.·Semple, B. D.
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Abstract

Traumatic brain injury (TBI) is a leading cause of long-term disability, and infections such as pneumonia represent a common and serious complication for TBI patients in the acute and subacute post-injury period. While the acute effects of infections have been documented, their long-term consequences on neurological and behavioral recovery as well as the potential precipitation of seizures after TBI remain unclear. This study aimed to investigate the chronic effects of Klebsiella pneumoniae infection following TBI, focusing on post-traumatic seizure development and neurobehavioral changes. Using a mouse model, we assessed the long-term effects of TBI and K. pneumoniae infection both in isolation and in combination. We found that, while infection with K. pneumoniae resulted in loss of body weight and increased mortality compared to vehicle-inoculated mice, there was no additional mortality in TBI animals. Further, although TBI alone induced chronic hyperactivity and reduced anxiety-like behaviors, K. pneumoniae lung infection had no lasting effect on these long-term outcomes. Thirdly, while TBI resulted in both spontaneous and evoked seizures long-term post-injury, early post-injury K. pneumoniae infection did not affect late onset seizure susceptibility. Together with recent findings on acute outcomes in this combined insult model of TBI and K. pneumoniae infection, this study suggests that K. pneumoniae does not significantly alter long-term neurobehavioral outcomes or the development of post-traumatic epilepsy. This research highlights the need to further explore the interplay between additional immune insults such as infection that may influence long-term recovery.

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Rewell, S. S., Shad, A., Chen, L., Chu, E., Wang, J., Chen, K., O'Brien, T. J., Li, J., Casillas-Espinosa, P. M., Semple, B. D.. 2024-12-17. Chronic Behavioral and Seizure Outcomes following Experimental Traumatic Brain Injury and Comorbid Klebsiella pneumoniae Lung Infection in Mice. https://doi.org/10.1101/2024.12.13.628278

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