Linked Life Data

16545803

Source:http://linkedlifedata.com/resource/pubmed/id/16545803

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-7-3
pubmed:abstractText
The complement system represents an important mediator of neuroinflammation in traumatic brain injury. We have previously shown that transgenic mice with central nervous system-targeted overexpression of Crry, a potent murine complement inhibitor at the level of C3 convertases, are protected from complement-mediated neuropathological sequelae in brain-injured mice. This knowledge was expanded in the present study to a pharmacological approach by the use of a recombinant Crry molecule (termed Crry-Ig) which was recently made available in a chimeric form fused to the non-complement fixing mouse IgG1 Fc region. In a standardized model of closed head injury in mice, the systemic injection of 1 mg Crry-Ig at 1 h and 24 h after trauma resulted in a significant neurological improvement for up to 7 days, as compared to vehicle-injected control mice (P < 0.05, repeated measures ANOVA). Furthermore, the extensive neuronal destruction seen in the hippocampal CA3/CA4 sublayers in head-injured mice with vehicle injection only was shown to be preserved - to a similar extent as in "sham"-operated mice - by the posttraumatic injection of Crry-Ig. Real-time RT-PCR analysis revealed that the post-treatment with Crry-Ig resulted in a significant up-regulation of candidate neuroprotective genes in the injured hemisphere (Bcl-2, C1-Inh, CD55, CD59), as compared to the vehicle control group (P < 0.01, unpaired Student's t test). Increased intracerebral Bcl-2 expression by Crry-Ig treatment was furthermore confirmed at the protein level by Western blot analysis. These data suggest that pharmacological complement inhibition represents a promising approach for attenuation of neuroinflammation and secondary neurodegeneration after head injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0014-4886
pubmed:author
pubmed:issnType
Print
pubmed:volume
199
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
454-64
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16545803-Animals, pubmed-meshheading:16545803-Behavior, Animal, pubmed-meshheading:16545803-Blotting, Western, pubmed-meshheading:16545803-Brain, pubmed-meshheading:16545803-Brain Injuries, pubmed-meshheading:16545803-Cell Survival, pubmed-meshheading:16545803-Complement System Proteins, pubmed-meshheading:16545803-Disease Models, Animal, pubmed-meshheading:16545803-Gene Expression, pubmed-meshheading:16545803-Immunohistochemistry, pubmed-meshheading:16545803-Male, pubmed-meshheading:16545803-Mice, pubmed-meshheading:16545803-Mice, Inbred C57BL, pubmed-meshheading:16545803-Neurons, pubmed-meshheading:16545803-Neuroprotective Agents, pubmed-meshheading:16545803-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:16545803-Psychomotor Performance, pubmed-meshheading:16545803-RNA, Messenger, pubmed-meshheading:16545803-Receptors, Complement, pubmed-meshheading:16545803-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16545803-Time Factors, pubmed-meshheading:16545803-Trauma Severity Indices
pubmed:year
2006
pubmed:articleTitle
Pharmacological complement inhibition at the C3 convertase level promotes neuronal survival, neuroprotective intracerebral gene expression, and neurological outcome after traumatic brain injury.
pubmed:affiliation
Department of Trauma and Reconstructive Surgery, Charité-University Medical School, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural