An Inflammatory Pulmonary Insult Post-TBI Worsens Subsequent Spatial Learning and Neurological Outcomes.

Jacovides, Christina L; Ahmed, Syed; Suto, Yujin; Paris, Andrew J; Leone, Ryan; McCarry, Jordan; Christofidou-Solomidou, Melpo; Kaplan, Lewis J; Smith, Douglas H; Holena, Daniel N; Schwab, C William; Pascual, Jose L

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 6m/s, depth 1.0mm) ± intratracheal lipopolysaccharide (LPS-2mg/kg in 0.1ml 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 (MWM) 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. MWM 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 in optimizing pulmonary care for brain-injured patients. STUDY TYPE This is a basic science Original Article and does not require a Level of Evidence.