Serum Amyloid A is Expressed in the Brain After Traumatic Brain Injury in a Sex-Dependent Manner.

Abstract

Serum amyloid A (SAA) is an acute phase protein upregulated in the liver after traumatic brain injury (TBI). So far, it has not been investigated whether SAA expression also occurs in the brain in response to TBI. For this, we performed a moderate controlled cortical impact injury in adult male and female mice and analyzed brain, blood, and liver samples at 6h, 1, 3, and 10days post-injury (dpi). We measured the levels of SAA in serum, brain and liver by western blot. Wealso used immunohistochemical techniques combined with in situ hybridization to determine SAA mRNA and proteinexpression in the brain. Our results revealed higher levels of SAA in the bloodstream in males compared to females at 6 h post-TBI. Liver and serum SAA protein showed a peak of expression at 1 dpi followed by a decrease at 3 to 10 dpi in both sexes. Both SAA mRNA and protein expression colocalize with astrocytes and macrophages/microglia in the cortex, corpus callosum, thalamus, and hippocampus afterTBI. For the first time, here we show that SAA isexpressed in the brain in response toTBI. Collectively, SAA expression was higherin males compared to females, and in association with the sex-dependent neuroinflammatory response after brain injury. We suggest that SAAcould be a crucial protein associated tothe acute neuroinflammationfollowing TBI, not only for its hepatic upregulationbut also for its expression in the injured brain.