Regional and temporal characterization of neuronal, glial, and axonal response after traumatic brain injury in the mouse

Fluid percussion injury (FPI) is a commonly used and clinically relevant mo del of traumatic brain injury (TBI) in the rat. Recently, our lab successfu lly adapted FPI to mice. To account for differences in response to injury b etween mice and rats and provide a foundation for further use of FPI in gen e-targeting studies, we sought to characterize the temporal and regional re sponse to FPI in male C57BL/6 mice. Animals were killed at 10 min, 24 h, an d 4, 7, 14, and 35 days (n = 3 for each group) after a very severe parasagi ttal FPI (> 4.0 atm) or sham injury (n = 3). Extensive numbers of damaged n eurons were consistently found in the ipsilateral cortex, thalamus, and hip pocampus by 10 min. This damage was nearly identical at 24 h, but quickly d eclined at subsequent time points. Activated microglia were found only in r egions of neuronal injury at the earliest time points. Glial fibrillary aci dic protein immunoreactivity reached significantly higher levels compared w ith controls at 7 days (P < 0.05) in the cortex, thalamus, and hippocampus and remained elevated for 35 days. White matter degeneration was present in all regions examined. This damage did not appear until at least day 4, but progressed up to day 35. The spatial pattern of damage we observed in mice after FPI is similar to that seen in rats. However, the temporal progressi on of neuronal injury in mice is comparatively abbreviated in the hippocamp us and thalamus. In conclusion, these results suggest that FPI in mice may be a particularly useful tool for studying mechanisms of TBI in gene-target ing studies.