title: Fresh-frozen plasma resuscitation after traumatic brain injury and shock attenuates extracellular nucleosome levels and deoxyribonuclease 1 depletion.
abstract: BACKGROUND
  Traumatic brain injury and shock are among the leading causes of trauma-related mortality. We have previously shown that fresh-frozen plasma (FFP) resuscitation reduces the size of brain lesion and associated swelling compared with crystalloids. We hypothesized that this effect would be associated with an attenuation of circulating nucleosome levels, a biomarker of injury with cytotoxic potential, through reconstitution of circulating deoxyribonuclease-1 (DNAse1), an enzyme identified as critical in nucleosome clearance from the circulation.
  
  
  METHODS
  Twelve swine underwent a protocol of traumatic brain injury followed by 40% volume-controlled hemorrhage. Animals were left in shock (mean arterial pressure of 35 mmHg) for 2 hours before they were resuscitated with normal saline (NS) or FFP. Circulating levels of nucleosomes and DNAse1 were measured whereas extracellular nucleosomes were quantified on brain histology. Lesion size and brain swelling were also quantified.
  
  
  RESULTS
  Nucleosome levels were significantly greater in the NS group 6 hours after resuscitation (0.32 mU vs 0.15 mU, P = .030) whereas DNAse1 levels were substantially greater in the FFP group (9.82 ng/mL vs 4.54 ng/mL, P = .010). Circulating nucleosomes levels correlated with lesion size (rho = 0.79, P = .002) as well as brain swelling (rho = 0.89, P < .001) whereas DNAse1 levels correlated with brain swelling (rho = -0.61, P = .036) but not lesion size (rho = -0.47, P = .124). Brain staining revealed nucleosome extracellularization in both groups, but this appeared more frequent in the NS-resuscitated animals.
  
  
  CONCLUSIONS
  Our results show that resuscitation with FFP attenuates circulating nucleosome levels and prevents DNAse1 depletion. These factors may play a role in the neuroprotective effects observed during early resuscitation with FFP.
authors.affiliation: Department of Surgery, Division of Trauma, Emergency Surgery and Surgical Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Sillesen
authors.forename: Guang
authors.initials: G
authors.lastname: Jin
authors.forename: Rahmi
authors.initials: R
authors.lastname: Oklu
authors.forename: Hassan
authors.initials: H
authors.lastname: Albadawi
authors.forename: Ayesha M
authors.initials: AM
authors.lastname: Imam
authors.forename: Cecilie H
authors.initials: CH
authors.lastname: Jepsen
authors.forename: John O
authors.initials: JO
authors.lastname: Hwabejire
authors.forename: Sisse R
authors.initials: SR
authors.lastname: Ostrowski
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
authors.forename: Lars S
authors.initials: LS
authors.lastname: Rasmussen
authors.forename: Hasan B
authors.initials: HB
authors.lastname: Alam
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000628:therapy*; D003850:Deoxyribonuclease I / Q000097:blood*; D005260:Female; D009707:Nucleosomes / Q000473:pathology*; D010949:Plasma; D012151:Resuscitation; D012769:Shock / Q000628:therapy*; D013552:Swine
chemical_list: D009707:Nucleosomes; D003850:Deoxyribonuclease I