Neuroglobin-overexpression reduces traumatic brain lesion size in mice

Abstract

Background: Accumulating evidence has demonstrated that over-expression of Neuroglobin (Ngb) is neuroprotective against hypoxic/ischemic brain injuries. In this study we tested the neuroprotective effects of Ngb over-expression against traumatic brain injury (TBI) in mice.

Results: Both Ngb over-expression transgenic (Ngb-Tg) and wild-type (WT) control mice were subjected to TBI induced by a controlled cortical impact (CCI) device. TBI significantly increased Ngb expression in the brains of both WT and Ngb-Tg mice, but Ngb-Tg mice had significantly higher Ngb protein levels at the pre-injury baseline and post-TBI. Production of oxidative tissue damage biomarker 3NT in the brain was significantly reduced in Ngb-Tg mice compared to WT controls at 6 hours after TBI. The traumatic brain lesion volume was significantly reduced in Ngb Tg mice compared to WT mice at 3 weeks after TBI; however, there were no significant differences in the recovery of sensorimotor and spatial memory functional deficits between Ngb-Tg and WT control mice for up to 3 weeks after TBI.

Conclusion: Ngb over-expression reduced traumatic lesion volume, which might partially be achieved by decreasing oxidative stress.

Figure 1

Ngb expression levels in mouse brains after TBI.A. Representative immunohistochemistry of Ngb protein expression in WT and Ngb-Tg mice cortex of peri-lesion area at sham animals and at 6 h after TBI. Original magnification × 200 in all photomicrographs. B. Representative western blot of Ngb protein expression in WT and Ngb-Tg mice cortex of peri-lesion area at sham animals and at 6 h after TBI, β-actin served as equal protein loading controls. C. Quantitation of Ngb protein levels. Data were expressed as mean ± SD. *P < 0.05, n = 5 per group.

Figure 2

Relative 3NT protein levels. Brian samples were collected at 6 h postinjury in sham and TBI-injured WT and Ngb-Tg mice. Slot-immunoblotting analysis was used to determine relative 3NT protein levels. Data were expressed as mean ± SD. *P < 0.05, n = 5 per group.

Figure 3

Spatial memory acquisitions in WT and Ngb-Tg mice after TBI.A. Morris water maze latencies were measured on days 15-21 for hidden and visible platform trials after TBI. B. Morris water maze latencies were measured on days 15-21 for probe trials after TBI. Data were expressed as mean ± SD. n = 15 for WT and 11 for Ngb-Tg per group, respectively.

Figure 4

Measurements of cortical lesion volume in WT and Ngb-Tg mice.A. Representative photomicrographs of the traumatic lesions in H&E stained WT and Ngb-Tg mouse brain sections at 21 days after TBI. B. Traumatic brain lesion size. Data were expressed as mean ± SD. *P < 0.05, n = 15 for WT and 11 for Ngb-Tg per group, respectively.