Ubiquitin reduces fluid shifts after traumatic brain injury

Steven A. Earle, Kenneth G Proctor, Mayur B. Patel, Matthias Majetschak

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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 μg/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.

Original languageEnglish
Pages (from-to)431-438
Number of pages8
JournalSurgery
Volume138
Issue number3
DOIs
StatePublished - Sep 1 2005

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Fluid Shifts
Ubiquitin
Resuscitation
Albumins
Traumatic Brain Hemorrhage
Cerebrospinal Fluid
Traumatic Brain Injury
Cerebrovascular Circulation
Urine
Intracranial Hypertension
Blood-Brain Barrier
Serum
Hematocrit
Half-Life

ASJC Scopus subject areas

  • Surgery

Cite this

Ubiquitin reduces fluid shifts after traumatic brain injury. / Earle, Steven A.; Proctor, Kenneth G; Patel, Mayur B.; Majetschak, Matthias.

In: Surgery, Vol. 138, No. 3, 01.09.2005, p. 431-438.

Research output: Contribution to journalArticle

Earle, Steven A. ; Proctor, Kenneth G ; Patel, Mayur B. ; Majetschak, Matthias. / Ubiquitin reduces fluid shifts after traumatic brain injury. In: Surgery. 2005 ; Vol. 138, No. 3. pp. 431-438.
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