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

Abstract

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.

Pulmonary infection in traumatic brain injury patients undergoing tracheostomy: predicators and nursing care

“…In clinical practice, tracheostomy may reduce the risk of VAP, avoid the complications of prolonged ventilation, and it helps in weaning patients from the ventilator if they are on the ventilator for a prolonged period. However, tracheostomy is one of the high-risk factors for pulmonary infection [ 17 , 18 ]. However, if patients with TBI are complicated with pulmonary infections, it may further affect their recovery effect and prognosis, and even lead to an increase in their mortality [ 19 ].…”

Beta blockade in TBI: Dose-dependent reductions in BBB leukocyte mobilization and permeability in vivo

“…Intravital microscopy (IVM) for in vivo assessment of the cerebral pial microcirculation was performed 48 hours post-CCI as described previously 17 . Under KXA anesthesia, the right jugular vein was cannulated, and a second 2.5-mm craniotomy was created anterior to the first and covered with a 5-mm coverslip (Fisher Scientific, Waltham, MA).…”

“…Intravital microscopy (IVM) for in vivo assessment of the cerebral pial microcirculation was performed 48 hours post-CCI as described previously. 17 Under KXA anesthesia, the right jugular vein was cannulated, and a second 2.5-mm craniotomy was created anterior to the first and covered with a 5-mm coverslip (Fisher Scientific, Waltham, MA). Secured in the stereotactic device, mice were transferred to an intravital microscope (ECLIPSE FN1; Nikon Instruments, Melville, NY) and received a 50-μL intrajugular injection of 0.3% rhodamine 6G (Sigma-Aldrich, St. Louis, MO) to fluorescently label circulating leukocytes (LEU) and enable visualization at a 590-nm λ epi-illumination emission exposure.…”

Aminophylline targets miR-128-3p/Slc7a11 axis to attenuate neuronal ferroptosis after traumatic brain injury

“…Sham-AMP (Sham-A) group received sham operation and AMP administration. The effects of AMP on cognitive and motor function of mice were assessed using neurological severity score (NSS) [30], Rotarod test [31], and morris water maze (MWM) [32], respectively (Fig. 1A).…”