Mannose binding lectin gene deficiency increases susceptibility to traumatic brain injury in mice.
Mannose binding lectin (MBL) initiates complement activation and exacerbates tissue damage after systemic ischemia/reperfusion. We tested the hypothesis that MBL activates complement and worsens outcome using two levels of controlled cortical impact (CCI) in mice. After moderate CCI (0.6 mm depth), MBL immunostaining was detected on injured endothelial cells of wild-type (WT) mice and C3d was detected in MBL KO (deficient in MBL A/C) and WT mice, suggesting that MBL is dispensable for terminal complement activation after CCI. Brain neutrophils, edema, blood-brain barrier permeability, gross histopathology, and motor dysfunction were similar in injured MBL KO and WT mice. In mice subjected to mild CCI (0.2 mm), MBL KO mice had almost two-fold increased acute CA3 cell degeneration at 6 h (P<0.01 versus WT). Naive MBL KO mice had decreased brain volume but performed similar to WT mice in two distinct Morris water maze (MWM) paradigms. However, injured MBL KO mice had impaired performance in cued platform trials (P<0.05 versus WT), suggesting a transient nonspatial learning deficit in injured MBL KO mice. The data suggest that MBL deficiency increases susceptibility to CCI through C3-independent mechanisms and that MBL-deficient patients may be at increased risk of poor outcome after traumatic brain injury.
Yager
Phoebe H
PH
Department of Pediatric Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 2129, USA.
You
Zerong
Z
Qin
Tao
T
Kim
Hyung-Hwan
HH
Takahashi
Kazue
K
Ezekowitz
Alan B
AB
Stahl
Gregory L
GL
Carroll
Michael C
MC
Whalen
Michael J
MJ
D000818:Animals; D001929:Brain Edema / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001930:Brain Injuries / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D016923:Cell Death / Q000502:physiology; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020127:Recovery of Function; D015427:Reperfusion Injury / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*
D003176:Complement C3; D037601:Mannose-Binding Lectin; C445639:Mbl2 protein, mouse; C069858:mannose binding protein A