title: Endothelin-1 is upregulated after traumatic brain injury: a cross-species, cross-model analysis.
abstract: OBJECTIVE
  This work was designed to compare levels of endothelin-1 following brain injury in both rat and porcine models of head injury. In a broader sense, this work also determines the feasibility of testing traumatic brain injury-related phenomenology across species and models.
  
  
  METHODS
  Male Sprague-Dawley rats (400-450 g) were subjected to traumatic brain injury using a weight acceleration impact injury device (n = 5 per group). Following impact, cerebrospinal fluid was collected for enzyme-linked immunosorbent assay analysis of endothelin-1 concentration using a standard endothelin-1 detection kit at 4 hours, 24 hours, 48 hours, and 7 days post-traumatic brain injury. Sham operated animals (n = 5) were used as controls. In another set of experiments, traumatic brain injury was induced in newborn and juvenile pigs (n = 6 per group) using a lateral fluid percussion model of brain injury. Cerebrospinal fluid was collected at 4 hours, 8 hours, 72 hours, and 7 days post-injury and endothelin-1 levels were measured using a radiolabeled kit.
  
  
  RESULTS
  Endothelin-1 levels rapidly increased from ∼35 in sham operated animals to over 200 pg/g tissue 4 hours post-impact in both rat cortex and hippocampus. This elevation was sustained through 48 hours post-impact. By 7 days post-injury, endothelin-1 levels returned to normal, control concentrations. This trend was consistent with the porcine model, being more pronounced in newborn versus juvenile pigs.
  
  
  CONCLUSIONS
  These results show that endothelin-1 peptide concentration elevation is a consistent finding between rat and pig and between weight acceleration and fluid percussion models of traumatic brain injury. This suggests that endothelin-1 elevation is not only a conserved phenomenon in different models of traumatic brain injury, but that it is a likely target for understanding the observed enhanced vascular response to traumatic brain injury and ultimately developing strategies to improve outcome following traumatic brain injury.
authors.affiliation: Department of Anesthesiology, University of Pennsylvania, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Armstead
authors.forename: Christian W
authors.initials: CW
authors.lastname: Kreipke
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply* / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D006624:Hippocampus / Q000098:blood supply* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D034421:Sus scrofa; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D019332:Endothelin-1