Ubiquitin reduces fluid shifts after traumatic brain injury.
BACKGROUND
Ubiquitin has well-described intracellular properties. Recent data also suggest pleiotropic effects of extracellular ubiquitin, including induction of apoptosis, regulation of immune functions, and therapeutic potential during fluid resuscitation from severe trauma. However, the actions of exogenous ubiquitin after traumatic brain injury (TBI) are unknown.


METHODS
Series 1: Thirty-five minutes after TBI and hemorrhage, 1.5 mg ubiquitin/kg (n = 5) or albumin (n = 5) intravenous was followed by fluid resuscitation to maintain mean arterial and cerebral perfusion pressure. Series 2: Ubiquitin (n = 5) or vehicle (n = 6) was administered after TBI only. Ubiquitin was measured with enzyme-linked immunosorbent assay in serum, urine (series 1), and cerebrospinal fluid (series 2) for 300 minutes.


RESULTS
Series 1: After intravenous bolus, serum ubiquitin peaked at t = 45 minutes with a half-life of 54 minutes. Recovery in urine was 10%. With albumin versus ubiquitin, 85% more resuscitation fluid was required to stabilize systemic and cerebral hemodynamics (P < .05 for t = 150 to 300 minutes), but hematocrit was similar. With albumin there were progressive increases in intracranial pressure, peak inspiratory pressure, and decreases in oxygenation. All were significantly attenuated by ubiquitin (all P < .05 vs albumin). Series 2: Intravenous ubiquitin altered cerebrospinal fluid ubiquitin with an increased time to peak (t = 88 +/- 13 min vs 45 +/- 7 min, P < .05) and area under the concentration-time curve (82 +/- 22 vs 23 +/- 11 microg/min(1)/mL(-1), P < .05).


CONCLUSIONS
After TBI, intravenous ubiquitin crossed the blood-brain barrier and significantly reduced third spacing of fluid into the brain and lung during resuscitation.
Earle
Steven A
SA
Division of Trauma and Surgical Critical Care, Ryder Trauma Center, Dewitt Daughtry Family Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Proctor
Kenneth G
KG
Patel
Mayur B
MB
Majetschak
Matthias
M
D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology* / Q000628:therapy; D002543:Cerebral Hemorrhage / Q000503:physiopathology / Q000628:therapy*; D004195:Disease Models, Animal; D005440:Fluid Therapy; D010952:Plasma Substitutes / Q000627:therapeutic use*; D012151:Resuscitation / Q000379:methods; D012709:Serum Albumin / Q000008:administration & dosage / Q000627:therapeutic use; D025801:Ubiquitin / Q000008:administration & dosage / Q000627:therapeutic use*
D010952:Plasma Substitutes; D012709:Serum Albumin; D025801:Ubiquitin