title: Hepatic expression of serum amyloid A1 is induced by traumatic brain injury and modulated by telmisartan.
abstract: Traumatic brain injury affects the whole body in addition to the direct impact on the brain. The systemic response to trauma is associated with the hepatic acute-phase response. To further characterize this response, we performed controlled cortical impact injury on male mice and determined the expression of serum amyloid A1 (SAA1), an apolipoprotein, induced at the early stages of the acute-phase response in liver and plasma. After cortical impact injury, induction of SAA1 was detectable in plasma at 6 hours post-injury and in liver at 1 day post-injury, followed by gradual diminution over time. In the liver, cortical impact injury increased neutrophil and macrophage infiltration, apoptosis, and expression of mRNA encoding the chemokines CXCL1 and CXCL10. An increase in angiotensin II AT1 receptor mRNA at 3 days post-injury was also observed. Administration of the AT1 receptor antagonist telmisartan 1 hour post-injury significantly decreased liver SAA1 levels and CXCL10 mRNA expression, but did not affect CXCL1 expression or the number of apoptotic cells or infiltrating leukocytes. To our knowledge, this is the first study to demonstrate that SAA1 is induced in the liver after traumatic brain injury and that telmisartan prevents this response. Elucidating the molecular pathogenesis of the liver after brain injury will assist in understanding the efficacy of therapeutic approaches to brain injury.
authors.affiliation: Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia. Electronic address: sonia.villapol@georgetown.edu.
authors.forename: Sonia
authors.initials: S
authors.lastname: Villapol
authors.affiliation: Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Kryndushkin
authors.affiliation: Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Balarezo
authors.affiliation: Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Campbell
authors.affiliation: Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, District of Columbia.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Saavedra
authors.affiliation: Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Frank P
authors.initials: FP
authors.lastname: Shewmaker
authors.affiliation: Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland; Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland. Electronic address: aviva.symes@usuhs.edu.
authors.forename: Aviva J
authors.initials: AJ
authors.lastname: Symes
mesh_terms: D000210:Acute-Phase Reaction / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D054360:Chemokine CXCL1 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; C114753:CXCL10 protein, human; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; C475895:Cxcl1 protein, mouse; C485433:Cxcl10 protein, mouse; D000685:Serum Amyloid A Protein; D000077333:Telmisartan