P11 – Serum Amyloid A Factor-1 Increases Inflammation in the Brain of Mice after Mild TBI

Author(s):
Joshua Gatson, Ming-Mei Liu, Joseph Minei, Steven Wolf, UT Southwestern Medical Center

Background: Following a mild traumatic brain injury (TBI) event, the secondary brain injury that persists after the initial blow to the head consists of excitotoxicity, decreased cerebral glucose levels, oxidant injury, mitochondrial dysfunction, inflammation, and neuronal cell death. With respect to inflammation, increased activation of the transcription, factor serum amyloid A factor-1 (SAF-1), results in increased levels of inflammation and degradation of the extracellular matrix in various tissue types.

Hypothesis: Here, we hypothesized that activation of SAF-1 increases in the brain after mild TBI and results in heightened neuro-inflammation during both acute and chronic time points.

Methods: In the current study, male mice were injured using the controlled cortical impact device. Using a closed-head mild TBI model, a midline incision was made to access the skull and the impactor tip was aligned directly on the skull on the sagittal suture midway between the bregma (-2.12 mm) and lambda sutures. The mice were injured at a depth of 1.5 mm, velocity of 3.5 m/sec, and a delay time of 100 msec. At 1, 3, 7, 14, and 30 days after injury, the animals were intra-cardially perfused with 0.9% saline followed by 10% phosphate-buffered formalin. The whole brain was removed, sliced, and stained for total and phosphorylated serum amyloid A factor-1 (SAF-1), microglial activation, and astrocyte activation/infiltration in the brain.

Results: In this study we found that following mild TBI an increase in the levels of phosphorylated SAF-1 was increased in the cortex and hippocampus at day 7 (p= 0.05) and 30 (p= 0.03) after injury. No increase was observed in the brain on day 1 and 3 after injury. The levels of SAF-1 correlated with an increase in the levels of activated microglia (p= 0.05) and astrocytes (p= 0.04) in the injured animals.

Conclusions: : An increase in phosphorylated SAF-1 levels in the brain may result in chronic inflammation and cognitive decline after mild TBI. SAF-1 may be target to reduce chronic inflammation and improve neurological outcomes after TBI.