Serum amyloid A is increased in children with abusive head trauma: a gel-based proteomic analysis

Abstract

Background: Abusive head trauma (AHT) is the leading cause of death from traumatic brain injury in infants and young children. Identification of mild AHT (Glasgow Coma Scale score: 13-15) is difficult because children can present with nonspecific symptoms and with no history of trauma. Methods: Two-dimensional difference gel electrophoresis combined with mass spectrometry was used to compare the serum protein profile of children with mild AHT and agematched controls. Protein changes were confirmed by western blots. Western blots were performed using serum from children with mild, moderate, and severe AHT to assess the effect of injury severity on protein intensity. The protein identifiedserum amyloid A (SAA)-was then measured by enzymelinked immunosorbent assay. results: Using serum from 18 mild AHT cases and 20 controls, there were ~1,000 protein spots; 2 were significantly different between groups. Both spots were identified as SAA. There was no relationship between protein levels and injury severity. SAA concentrations measured by enzyme-linked immunosorbent assay were increased in cases vs. controls. conclusion: SAA may be a potential biomarker to identify children with mild AHT who present for medical care without a history of trauma and who might otherwise not be recognized as needing a head computed tomography.

Biomarkers of Vascular Integrity in Traumatic Brain Injury and Correlation with Cerebrovascular Reactivity

“…Increased ratio of Ang-1/ Ang-2 may contribute to breakdown of blood-brain barrier after brain injury, and angiopoietins are thus considered hallmarks of vascular injury and promising therapeutic targets in brain injury [3]. Our results are also consistent with other study reports that SAA may be a potential biomarker for mild TBI and a biomarker in response to inflammation and TBI [4]; Ang-1 and tyrosine kinase-2 (Tie-2) expressed on actively growing endothelium receptor for angiopoietin ligands may be protective factors for vascular integrity, and exercise improves recovery after ischemic brain injury by inducing the expression of Ang-1 and Tie-2 [6]; six biomarkers in CSF (IL-15, MCP-1, VEGFR-1, sICAM1, sVCAM-1, and VEGF-D) correlated with the tau levels in CSF, inflammation, vascular injury, and angiogenesis [10].…”

“…TVI is a common finding in TBI. For example, angiopoietins (Ang) are hallmarks of vascular injury [3]; serum SAA, which has been found to increase after abusive head trauma not evident from neuroimaging, is a potential biomarker for mild TBI [4]; levels of TNF and sICAM-1 in the cerebrospinal fluid (CSF) are increased after severe TBI [5]. Exercise improves recovery after ischemic brain injury by inducing the expression of Ang-1 and Tie-2, indicating their protective potentials for vascular integrity [6].…”

Hepatic alterations are accompanied by changes to bile acid transporter-expressing neurons in the hypothalamus after traumatic brain injury

“…A major role for the liver in initiating the APR and mediating the inflammatory response has been well-described17181920. Triggers for the APR include elevations of the cytokines IL-1β, IL-6 and TNF-α, which can bind directly to hepatocytes and induce the synthesis and subsequent release of acute phase response proteins.…”

“…The APR is coordinated primarily by the liver17 via the release of regulatory acute-phase proteins9. The positive acute-phase proteins include, C-reactive protein (CRP), haptoglobin, serum amyloid A (SAA), and serum amyloid P (SAP)181920. Once released, these proteins modulate the inflammatory response, stimulate the complement system, scavenge free radicals and neutralize enzymatic activity16.…”

Current status of fluid biomarkers in mild traumatic brain injury

“…In a human study, Gao et al (2014) evaluated serum (~12 h) from infants that had sustained a mild abusive head injury (AHI) with an acute extra-axial hemorrhage. Beginning with 2D-DIGE combined with LC-MS, the two spots with the highest spot change between control and injury were identified as serum amyloid A (SAA).…”