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Updated: Jan 23, 2026
Inducing Post-Traumatic Epilepsy in a Mouse Model of Repetitive Diffuse Traumatic Brain Injury
Published on: February 10, 2020
An inflammatory pulmonary insult post-traumatic brain injury worsens subsequent spatial learning and neurological
Christina L Jacovides1, Syed Ahmed, Yujin Suto
1From the Division of Traumatology, Surgical Critical Care and Emergency Surgery (C.L.J., S.A., R.L., J.M., L.J.K., D.N.H., C.W.S., J.L.P.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Emergency and Critical Care Medicine (Y.S.), Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan; Department of Medicine (A.J.P.), University of Pennsylvania, Philadelphia, PA; Department of Medicine, Pulmonary, Allergy and Critical Care Division (M.C-S.), University of Pennsylvania, Philadelphia, Pennsylvania; and Center for Brain Injury and Repair, Department of Neurosurgery (D.H.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Background:
Severe traumatic brain injury (TBI) patients are at high risk for early aspiration and pneumonia. How pneumonia impacts neurological recovery after TBI is not well characterized. We hypothesized that, independent of the cerebral injury, pneumonia after TBI delays and worsens neurological recovery and cognitive outcomes.
Methods:
Fifteen CD1 male mice were randomized to sham craniotomy or severe TBI (controlled cortical impact [CCI] - velocity 6 m/s, depth 1.0 mm) ± intratracheal lipopolysaccharide (LPS-2 mg/kg in 0.1 mL saline) as a pneumonia bioeffector. Neurological functional recovery by Garcia Neurologic Testing (GNT) and body weight loss were recorded daily for 14 days. On Days 6-14, animals underwent Morris Water Maze learning and memory testing with cued trials (platform visible), spatial learning trials (platform invisible, spatial cues present), and probe (memory) trials (platform removed, spatial clues present). Intergroup differences were assessed by the Kruskal-Wallis test with Bonferroni correction (p < 0.05).
Results:
Weight loss was greatest in the CCI + LPS group (maximum 24% on Day 3 vs. 8% [Sham], 7% [CCI], both on Day 1). GNT was lowest in CCI + LPS during the first week. Morris Water Maze testing demonstrated greater spatial learning impairment in the CCI + LPS group vs. Sham or CCI counterparts. Cued learning and long-term memory were worse in CCI + LPS and CCI as compared to Sham.
Conclusion:
A pneumonia bioeffector insult after TBI worsens weight loss and mortality in a rodent model. Not only is spatial learning impaired, but animals are more debilitated and have worse neurologic performance. Understanding the adverse effects of pneumonia on TBI recovery is the first step d patients.
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