There is a significant need for novel treatments that will improve traumatic 
brain injury (TBI) outcomes. One potential neuroprotective mechanism is to 
increase oxygen binding proteins such as neuroglobin. Neuroglobin has a high 
affinity for oxygen, is an effective free radical scavenger, and is 
neuroprotective within the brain following hypoxia and ischemia. The purpose of 
this study was to determine whether neuroglobin overexpression improves 
sensorimotor outcomes following TBI in transgenic neuroglobin overexpressing 
(NGB) mice. Additional study aims were to determine if and when an endogenous 
neuroglobin response occurred following TBI in wild-type (WT) mice, and in what 
brain regions and cell types the response occurred. Controlled cortical impact 
(CCI) was performed in adult (5 month) C57/BL6 WT mice, and NGB mice 
constitutively overexpressing neuroglobin via the chicken beta actin promoter 
coupled with the cytomegalovirus distal enhancer. The gridwalk task was used for 
sensorimotor testing of both WT and NGB mice, prior to injury, and at 2, 3, and 
7 days post-TBI. NGB mice displayed significant reductions in the average number 
of foot faults per minute walking at 2, 3, and 7 days post-TBI when compared to 
WT mice at each time point. Neuroglobin mRNA expression was assessed in the 
injured cortex of WT mice prior to injury, and at 1, 3, 7, and 14 days post-TBI 
using quantitative real time polymerase chain reaction (qRT-PCR). Neuroglobin 
mRNA was significantly increased at 7 days post-TBI. Immunostaining showed 
neuroglobin primarily localized to neurons and glial cells in the injured cortex 
and ipsilateral hippocampus of WT mice, while neuroglobin was present in all 
brain regions of NGB mice at 7 days post-TBI. These results showed that 
overexpression of neuroglobin reduced sensorimotor deficits following TBI, and 
that an endogenous increase in neuroglobin expression occurs during the subacute 
period. Increasing neuroglobin expression through novel therapeutic 
interventions during the acute period after TBI may improve recovery.