• Eric Anthony Sribnick, Timothy Warner, and Mark Hall.
• Nationwide Children's Hospital, 2650, 700 Children's Drive, Columbus, Ohio, United States, 43205-2664; eric.sribnick@nationwidechildrens.org.
• J. Neurotrauma. 2024 Apr 16.

AbstractTraumatic brain injury (TBI) is a common cause of morbidity and mortality in children. We have previously shown that TBI with a concurrent extra-cranial injury reliably leads to post-injury suppression of the innate and adaptive immune systems. In patients with post-injury immune suppression, if immune function could be preserved, this might represent a therapeutic opportunity. As such, we examined, in an animal injury model, whether systemic administration of GM-CSF could reverse post-injury immune suppression and whether treatment was associated with neuroinflammation or functional deficit. Prepubescent male rats were injured using a controlled cortical impact model and then removal of 25% blood volume (TBI/H). Sham animals underwent surgery without injury induction, and the treatment groups were: sham and injured animals treated with either saline vehicle or 50 μg/kg GM-CSF. GM-CSF was given following injury and then daily until sacrifice at post-injury day 7. Immune function was measured by assessing TNF-α levels in whole blood and spleen following ex-vivo stimulation with poke weed mitogen (PWM). Brain samples were assessed by multiplex ELISA for cytokine levels and by immunohistochemistry for microglia and astrocyte proliferation. Neuronal cell count was examined using cresyl violet staining. Motor coordination was evaluated using the Rotarod performance test. Treatment with GM-CSF was associated with a significantly increased response to PWM in both whole blood and spleen. GM-CSF in injured animals did not lead to increases in levels of pro-inflammatory cytokines in brain samples but was associated with significant increases in counted astrocytes. Finally, while injured animals treated with saline showed a significant impairment on behavioral testing, injured animals treated with GM-CSF performed similar to uninjured animals. GM-CSF treatment in animals with combined injury led to increased systemic immune cell response in whole blood and spleen in the acute phase following injury. Improved immune response was not associated with elevated pro-inflammatory cytokine levels in brain or functional impairment.

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