Deficiency of complement receptors CR2/CR1 in Cr2-/- mice reduces the extent of secondary brain damage after closed head injury

Journal of Neuroinflammation

Philip F Stahel¹  V Michael Holers²  Liudmila Kulik²  Michael A Flierl³  Jenée Patane³  Justin T Losacco³  Ashley L Bolden³  Sebastian Weckbach³  Chesleigh N Keene³  Megan C Rich³  Miriam D Neher³ 

[1] Department of Neurosurgery, Denver Health Medical Center, University of Colorado School of Medicine, 777 Bannock Street, Denver CO 80204, USA;Department of Medicine and Department of Immunology, University of Colorado, Campus Box B115, Barbara Davis Center, Aurora CO 80045, USA;Department of Orthopedic Surgery, Denver Health Medical Center, University of Colorado School of Medicine, 777 Bannock Street, Denver CO 80204, USA

关键词: Secondary brain injury;    Cr2^-/- mice;    Complement receptor;    Neuroinflammation;    Closed head injury;   

Others  :  803964
DOI  :  10.1186/1742-2094-11-95

 received in 2014-01-08, accepted in 2014-05-12,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Neher et al.; licensee BioMed Central Ltd.

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