Activation of complement pathways after contusion-induced spinal cord injury.
Previous studies have shown that a cellular inflammatory response is initiated, and inflammatory cytokines are synthesized, following experimental spinal cord injury (SCI). In the present study, we tested the hypothesis that the complement cascade, a major component of both the innate and adaptive immune response, is also activated following experimental SCI. We investigated the pathways, cellular localization, timecourse, and degree of complement activation in rat spinal cord following acute contusion-induced SCI using the New York University (NYU) weight drop impactor. Mild and severe injuries (12.5 and 50 mm drop heights) at 1, 7, and 42 days post injury time points were evaluated. Classical (C1q and C4), alternative (Factor B) and terminal (C5b-9) complement pathways were strongly activated within 1 day of SCI. Complement protein immunoreactivity was predominantly found in cell types vulnerable to degeneration, neurons and oligodendrocytes, and was not generally observed in inflammatory or astroglial cells. Surprisingly, immunoreactivity for complement proteins was also evident 6 weeks after injury, and complement activation was observed as far as 20 mm rostral to the site of injury. Axonal staining by C1q and Factor B was also observed, suggesting a potential role for the complement cascade in demyelination or axonal degeneration. These data support the hypothesis that complement activation plays a role in SCI.
Anderson
Aileen J
AJ
Department of Physical Medicine and Rehabilitation, and the Reeve-Irvine Center, University of California, Irvine, California 92696-4540, USA. aja@uci.edu
Robert
Stephanie
S
Huang
Wencheng
W
Young
Wise
W
Cotman
Carl W
CW
D000818:Animals; D002452:Cell Count; D003167:Complement Activation / Q000276:immunology*; D003165:Complement System Proteins / Q000378:metabolism; D009457:Neuroglia / Q000276:immunology; D009474:Neurons / Q000276:immunology; D051381:Rats; D020318:Rats, Long-Evans; D013119:Spinal Cord Injuries / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D015599:Trauma Severity Indices
D003165:Complement System Proteins