| First Author | Leinhase I | Year | 2006 |
| Journal | Exp Neurol | Volume | 199 |
| Issue | 2 | Pages | 454-64 |
| PubMed ID | 16545803 | Mgi Jnum | J:111296 |
| Mgi Id | MGI:3653567 | Doi | 10.1016/j.expneurol.2006.01.033 |
| Citation | Leinhase I, et al. (2006) Pharmacological complement inhibition at the C3 convertase level promotes neuronal survival, neuroprotective intracerebral gene expression, and neurological outcome after traumatic brain injury. Exp Neurol 199(2):454-64 |
| 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. |
