Traumatic brain injury (TBI) is an international health concern with a complex pathogenesis resulting in major long-term neurological, neurocognitive, and neuropsychiatric outcomes. Although
neuroinflammation has been identified as an important pathophysiological process resulting from TBI, the function of specific inflammatory mediators in the aftermath of TBI remains poorly understood.
Granulocyte-macrophage colony-stimulating factor (
GM-CSF) is an inflammatory
cytokine that has been reported to have
neuroprotective effects in various animal models of
neurodegenerative disease that share pathological similarities with TBI. The importance of
GM-CSF in TBI has yet to be studied, however. We examined the role of
GM-CSF in TBI by comparing the effects of a lateral fluid percussion (LFP) injury or
sham injury in
GM-CSF gene deficient (
GM-CSF(-/-)) versus wild-type (WT) mice. After a 3-month recovery interval, mice were assessed using neuroimaging and behavioral outcomes. All mice given a LFP injury displayed significant brain
atrophy and behavioral impairments compared with those given
sham-
injuries; however, this was significantly worse in the
GM-CSF(-/-) mice compared with the WT mice.
GM-CSF(-/-) mice given LFP injury also had reduced
astrogliosis compared with their WT counterparts. These novel findings indicate that the inflammatory mediator,
GM-CSF, may have significant protective properties in the chronic sequelae of experimental TBI and suggest that further research investigating
GM-CSF and its potential benefits in the injured brain is warranted.