A CD11d monoclonal antibody treatment reduces tissue injury and improves neurological outcome after fluid percussion brain injury in rats.
Traumatic brain injury (TBI) is an international health concern often resulting in chronic neurological abnormalities, including cognitive deficits, emotional disturbances, and motor impairments. An anti-CD11d monoclonal antibody that blocks the CD11d/CD18 integrin and vascular cell adhesion molecule (VCAM)-1 interaction following experimental spinal cord injury improves functional recovery, while reducing the intraspinal number of neutrophils and macrophages, oxidative activity, and tissue damage. Since the mechanisms of secondary injury in the brain and spinal cord are similar, we designed a study to evaluate fully the effects of anti-CD11d treatment after a moderate lateral fluid percussion TBI in the rat. Rats were treated at 2 h after TBI with either the anti-CD11d antibody or an isotype-matched control antibody 1B7, and both short (24- to 72-h) and long (4-week) recovery periods were examined. The anti-CD11d integrin treatment reduced neutrophil and macrophage levels in the injured brain, with concomitant reductions in lipid peroxidation, astrocyte activation, amyloid precursor protein accumulation, and neuronal loss. The reduced neuroinflammation seen in anti-CD11d-treated rats correlated with improved performance on a number of behavioral tests. At 24 h, the anti-CD11d group performed significantly better than the 1B7 controls on several water maze measures of spatial cognition. At 4 weeks post-injury the anti-CD11d-treated rats had better sensorimotor function as assessed by the beam task, and reduced anxiety-like behaviors, as evidenced by elevated-plus maze testing, compared to 1B7 controls. These findings suggest that neuroinflammation is associated with behavioral deficits after TBI, and that anti-CD11d antibody treatment is a viable strategy to improve neurological outcomes after TBI.
Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
Feng
F
Bao
Sandy R
SR
Shultz
Jeff D
JD
Hepburn
Vanessa
V
Omana
Lynne C
LC
Weaver
Donald P
DP
Cain
Arthur
A
Brown
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001930:Brain Injuries / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology*; D018845:CD11 Antigens / Q000276:immunology* / Q000378:metabolism; D018821:CD18 Antigens / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D020127:Recovery of Function / Q000276:immunology; D016896:Treatment Outcome
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D018821:CD18 Antigens