Document Detail

Ubiquitin reduces contusion volume after controlled cortical impact injury in rats.
MedLine Citation:
PMID:  17892413     Owner:  NLM     Status:  MEDLINE    
Recent data suggest that ubiquitin has anti-inflammatory properties and therapeutic potential after severe trauma and brain injuries. However, direct evidence for its neuroprotective effects has not yet been provided. We hypothesized that ubiquitin treatment is neuroprotective, and thus reduces brain edema formation and cortical contusion volume after closed traumatic brain injuries. To test this hypothesis, a focal cortical contusion was induced using a controlled cortical impact (CCI) model in Sprague-Dawley rats. Animals (n = 27) were randomized to either 1.5 mg/kg ubiquitin or vehicle (placebo) intravenously within 5 min after CCI. Blood pressure, arterial blood gases (ABG) and intracranial pressure (ICP) were monitored. Ubiquitin serum and cerebrospinal fluid levels were measured by ELISA. Brain water content was quantified gravimetrically after 24 h and cerebral contusion volume was determined in triphenyltetrazolium-chloride stained brains after 7 days. All animals recovered to normal activity. ICP and cerebral perfusion pressures were normal at the end of the observation period. Ubiquitin serum and CSF levels at 24 h and 7 days after CCI were similar in both groups. With ubiquitin brain water content of the injured hemisphere was slightly lower (n = 6/group; 79.97 +/- 0.29% vs. 81.11 +/- 0.52%; p = 0.08). Cortical contusion volume was significantly lower with ubiquitin (n = 7-8/group; 32.88 +/- 2.1 mm(3) vs. 43.96 +/- 4.56 mm(3); p = 0.025). This study shows that ubiquitin treatment after brain injury has direct neuroprotective effects, as demonstrated by improved brain morphology 7 days after brain injury. In connection with its beneficial effects in our previous studies, these data suggest ubiquitin as a promising candidate protein therapeutic for the treatment of brain injuries.
Martin Griebenow; Pablo Casalis; Christian Woiciechowsky; Matthias Majetschak; Ulrich-Wilhelm Thomale
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neurotrauma     Volume:  24     ISSN:  0897-7151     ISO Abbreviation:  J. Neurotrauma     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-09-25     Completed Date:  2007-11-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8811626     Medline TA:  J Neurotrauma     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1529-35     Citation Subset:  IM    
Department of Neurosurgery, Charité, Virchow Medical Center, Humboldt University, Berlin, Germany.
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MeSH Terms
Blood Pressure / drug effects
Brain Edema / drug therapy,  etiology,  pathology
Brain Injuries / drug therapy*,  etiology,  pathology*
Enzyme-Linked Immunosorbent Assay
Head Injuries, Closed / complications,  drug therapy*,  pathology
Intracranial Pressure / drug effects
Neuroprotective Agents / blood,  therapeutic use*
Rats, Sprague-Dawley
Ubiquitin / analysis,  therapeutic use*
Reg. No./Substance:
0/Neuroprotective Agents; 0/Ubiquitin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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