Vaccinia virus complement control protein enhances functional recovery after traumatic brain injury.
Inflammation is a major contributor to the neuropathological consequences of traumatic brain injury (TBI). Previous studies have shown that proinflammatory complement activation fragments are present in the injured brain within the first 24 h after trauma. To investigate whether complement activation within the injured brain leads to the neuropathology and subsequent functional impairment associated with TBI, we examined what effect administration of a complement inhibitor, the vaccinia virus complement control protein (VCP), would have on spatial learning and memory in brain injured rats, as measured using the Morris Water Maze (MWM) procedure. Animals were subjected to a lateral fluid percussion brain injury of moderate severity and, 15 min later, received a 10-microL injection of either full-length VCP, a truncated version of VCP (VCPt), which lacks the complement inhibitory activity but retains the heparin binding activity of VCP, or saline directly into the cortex. Results of such intervention indicated that, at 2 weeks postinjury, both VCP and VCPt treatment attenuated impairments in spatial memory, but not neuropathological damage, as compared to the saline treated controls. These results were surprising and suggest that the neuroprotective effects following administration of VCP after acute brain injury are mediated by mechanisms other than complement inhibition. Potential mechanisms are discussed.
Hicks
Ramona R
RR
Department of Rehabilitation Medicine, University of Washington, Seattle, Washington, USA.
Keeling
Kristen L
KL
Yang
Ming-Yan
MY
Smith
Scott A
SA
Simons
Ann M
AM
Kotwal
Girish J
GJ
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy*; D004660:Encephalitis / Q000188:drug therapy; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy; D008845:Microinjections; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D014764:Viral Proteins / Q000494:pharmacology*
D010446:Peptide Fragments; D014764:Viral Proteins; C066459:complement-control protein, Vaccinia virus