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An inflammatory pulmonary insult post-traumatic brain injury worsens subsequent spatial learning and neurological outcomes

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

Journal of Trauma and Acute Care Surgery: September 2019 - Volume 87 - Issue 3 - p 552–558
doi: 10.1097/TA.0000000000002403

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.

From 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.

Submitted: December 1, 2018, Revised: May 2, 2019, Accepted: May 22, 2019, Published online: June 13, 2019.

This work was a podium presentation at 32nd Annual Meeting of the Eastern Association for the Surgery of Trauma, Jan 15–19, 2019 in Austin, TX.

Address for reprints: Jose L. Pascual, MD, PhD, Division of Traumatology, Surgical Clinical Care and Emergency Surgery, University of Pennsylvania Perelman School of Medicine, Rm 108, 1st Floor Suite, 51 N 39th Street, Medical Office Building, 120, Philadelphia, PA 19104; email:

Online date: June 13, 2019

© 2019 Lippincott Williams & Wilkins, Inc.