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 6 h, 1, 3, and 10 days post-injury (dpi). We measured the levels of SAA in serum, brain and liver by western blot. We also used immunohistochemical techniques combined with in situ hybridization to determine SAA mRNA and protein expression 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 after TBI. For the first time, here we show that SAA is expressed in the brain in response to TBI. Collectively, SAA expression was higher in males compared to females, and in association with the sex-dependent neuroinflammatory response after brain injury. We suggest that SAA could be a crucial protein associated to the acute neuroinflammation following TBI, not only for its hepatic upregulation but also for its expression in the injured brain.

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Acknowledgements

We thank the master’s degree in Biochemistry and Molecular Biology Program at Georgetown University for the support.

Funding

This work was supported by R03NS095038 (SV) grant from the National Institute for Neurological Disorders and Stroke (NINDS), and funds from Houston Methodist Research Institute.

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SS, BM, EW, and SV performed the experiments, and contributed to the generation of all Figures and Table. S.V. performed the surgeries on mice and designed the study. E.W., S.S and S.V analyzed the data. The manuscript was written through the contributions of all authors. All authors approved the final version of the manuscript.

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Correspondence to Sonia Villapol.

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All animal procedures were in line with institutional guidelines and were approved by Institutional Animal Care and Use Committee (IACUC) of the core animal facility (Georgetown University and Houston Methodist Research Institute), and were conducted following the NRC guide to the Care and Use of Laboratory Animals.

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Soriano, S., Moffet, B., Wicker, E. et al. Serum Amyloid A is Expressed in the Brain After Traumatic Brain Injury in a Sex-Dependent Manner. Cell Mol Neurobiol 40, 1199–1211 (2020). https://doi.org/10.1007/s10571-020-00808-3

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Keywords

  • Neuroinflammation
  • Brain trauma
  • Acute phase response
  • Microglia
  • Neutrophil accumulation