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Investigating Alterations in Caecum Microbiota After Traumatic Brain Injury in Mice
Published on: September 19, 2019
Granulocyte-macrophage colony-stimulating factor reduces lung bacterial load following traumatic brain injury and
Ghaith A Bahader1, Timothy Warner1, Mark W Hall1,2
1Center for Clinical and Translation Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH.
Insights
Granulocyte-macrophage colony-stimulating factor (GM-CSF) can improve immune function and reduce lung infections in juvenile rats after traumatic brain injury (TBI) and hemorrhage. This therapy shows promise for managing post-injury infections in polytrauma patients.
Area of Science:
- Neuroscience
- Immunology
- Critical Care Medicine
Background:
- Severe traumatic brain injury (TBI), particularly polytrauma, increases children's risk of mortality and nosocomial respiratory infections.
- Post-injury immunosuppression is implicated in these infections, but mechanisms and treatments remain unclear.
Purpose of the Study:
- To investigate the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) in mitigating nosocomial infections following a polytrauma TBI model in prepubescent rats.
- To assess GM-CSF's impact on immune response and bacterial clearance without exacerbating brain injury.
Main Methods:
- A polytrauma model was created in rats using controlled cortical impact TBI, hemorrhage, and Streptococcus pneumoniae inoculation.
- Animals received daily intraperitoneal injections of saline or GM-CSF for two days post-injury.
- Immune responses were analyzed in blood, spleen, and brain; bacterial load was quantified in lung tissue.
Main Results:
- GM-CSF treatment enhanced innate immunity by increasing blood monocyte expression of MHC II molecules.
- Significant increases in splenic CD3+ T-cells were observed in GM-CSF treated rats compared to controls.
- GM-CSF significantly reduced bacterial load in the lungs without increasing glial activation, neuronal loss, or cognitive deficits.
Conclusions:
- GM-CSF effectively bolsters immune function and combats bacterial infections in a preclinical model of polytrauma TBI.
- GM-CSF demonstrates potential as a therapeutic agent to reduce the incidence of nosocomial infections in pediatric patients with severe TBI and polytrauma.
Abstract:
Traumatic brain injury (TBI) in children is associated with high rates of morbidity and mortality. Nosocomial respiratory infections are common following severe TBI, especially with polytraumatic TBI. Although post-injury immunosuppression has been identified as a potential contributor to nosocomial infection, the underlying mechanism and optimal therapy are poorly understood. In this study, we used a combined model of TBI plus extra-cranial hemorrhage followed by intranasal inoculation with Streptococcus pneumoniae to model the clinical scenario of polytrauma TBI and post-injury infection. Briefly, 28-day (prepubescent) rats received either sham injury or prefrontal controlled cortical impact injury plus removal of 25% of blood volume through femoral cannulation. Saline or 50µg/kg granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered intraperitoneally daily for 2 days. Post-injury immune response was assessed in the blood, spleen, and brain using different immunologic techniques, while bacterial clearance was examined by plating lung tissue. Our results show that GM-CSF enhanced innate immune function by increasing the percentage of blood monocytes expressing elevated levels of MHC II molecules. GM-CSF also significantly increased splenic CD3 + T-cells, compared to the saline-treated injury group. Moreover, increased lung bacterial load (colony-forming units) was significantly reduced with GM-CSF treatment. Treatment with GM-CSF was not associated with an increase in brain glial activation, neuronal loss, or memory dysfunction. This study highlights the potential role of GM-CSF as a therapy to address the increased risk of nosocomial infections following polytraumatic TBI.
