Granulocyte-Macrophage Colony-Stimulating Factor Is Neuroprotective in Experimental Traumatic Brain Injury

Abstract

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.

Neurodegeneration and Sensorimotor Deficits in the Mouse Model of Traumatic Brain Injury

“…Our result agrees with previous studies that demonstrates progressive brain atrophy and sensorimotor deficits in rodent model of traumatic brain injury [38][39][40][41]. The parietal lobes and their related circuitry are particularly more vulnerable to traumatic damage; hence executive dysfunction is prevalent [42,43].…”

“…Taken together, our data support that secondary injury exacerbates sensorimotor deficits after TBI and directly compliment previously reported in experimental brain-injury studies [38,39]. We interpret these findings to indicate that neurodegeneration following FPI exacerbates sensorimotor deficits and thus provides direct evidence that incidence of neurodegeneration after FPI may potentially result in increased neurological deficits and thereby, warrant strict monitoring of these events.…”

Tibial Fracture Exacerbates Traumatic Brain Injury Outcomes and Neuroinflammation in a Novel Mouse Model of Multitrauma

“…Apnea time, loss of consciousness, and self-righting reflex time were all recorded immediately after the injury as indicators of injury outcome (Table 1). 14 If apnea persisted for longer than 10 seconds, then mice were resuscitated with pure oxygen. 14,15 Both the MULTI and TBI groups had increased apnea, hindlimb withdrawal, and selfrighting reflex times compared with SHAM and FX groups. All mice received 0.05 mg/kg of buprenorphine analgesic subcutaneously.…”

“…14,15 The mouse was placed in a clear plastic box and put under isoflurane anesthesia with 3% isoflurane. Once sedated, mice were fixated supinely with a stereotactic frame.…”

Glioblastoma-synthesized G-CSF and GM-CSF contribute to growth and immunosuppression: Potential therapeutic benefit from dapsone, fenofibrate, and ribavirin

“…10 GM-CSF is neuroprotective after a wide range of neurotrauma, exerting neuroprotective effects by diminishing expression of apoptosis-related genes. [11][12][13][14][15] …”