Journal
JOURNAL OF NEUROINFLAMMATION
Volume 11, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1742-2094-11-95
Keywords
Closed head injury; Neuroinflammation; Complement receptor; Cr2(-/-) mice; Secondary brain injury
Categories
Funding
- Colorado Traumatic Brain Injury Trust Fund/Colorado Brain Injury Program
- German Research Foundation (DFG)
- NIH [AR051749]
Ask authors/readers for more resources
Complement activation at the C3 convertase level has been associated with acute neuroinflammation and secondary brain injury after severe head trauma. The present study was designed to test the hypothesis that Cr2(-/-) mice, which lack the receptors CR2/CD21 and CR1/CD35 for complement C3-derived activation fragments, are protected from adverse sequelae of experimental closed head injury. Adult wild-type mice and Cr2(-/-) mice on a C57BL/6 genetic background were subjected to focal closed head injury using a standardized weight-drop device. Head-injured Cr2(-/-) mice showed significantly improved neurological outcomes for up to 72 hours after trauma and a significantly decreased post-injury mortality when compared to wild-type mice. In addition, the Cr2(-/-) genotype was associated with a decreased extent of neuronal cell death at seven days post-injury. Western blot analysis revealed that complement C3 levels were reduced in the injured brain hemispheres of Cr2(-/-) mice, whereas plasma C3 levels remained unchanged, compared to wild-type mice. Finally, head-injured Cr2(-/-) had an attenuated extent of post-injury C3 tissue deposition, decreased astrocytosis and microglial activation, and attenuated immunoglobulin M deposition in injured brains compared to wild-type mice. Targeting of these receptors for complement C3 fragments (CR2/CR1) may represent a promising future approach for therapeutic immunomodulation after traumatic brain injury.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available