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Updated: Jul 8, 2026
Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice
Published on: September 28, 2022
Mannose binding lectin gene deficiency increases susceptibility to traumatic brain injury in mice
Phoebe H Yager1, Zerong You, Tao Qin
1Department of Pediatric Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 2129, USA.
Abstract:
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.
Insights
Mannose-binding lectin (MBL) deficiency increases susceptibility to traumatic brain injury in mice. MBL-deficient mice show greater neuronal damage and impaired learning after injury, suggesting MBL may protect against TBI.
Area of Science:
- Neuroscience
- Immunology
- Complement System
Background:
- Mannose-binding lectin (MBL) initiates complement activation and can worsen tissue damage following ischemia/reperfusion.
- The role of MBL in traumatic brain injury (TBI) and its impact on complement activation and neurological outcomes remains unclear.
Purpose of the Study:
- To investigate the role of MBL in the context of controlled cortical impact (CCI), a model of TBI.
- To determine if MBL deficiency affects complement activation, neuronal damage, and functional outcomes after TBI.
Main Methods:
- Controlled cortical impact (CCI) was induced in wild-type (WT) and MBL-deficient (MBL KO) mice at two severity levels (moderate and mild).
- Immunostaining for MBL and complement component C3d was performed on brain tissue.
- Evaluated outcomes included brain neutrophils, edema, blood-brain barrier permeability, histopathology, and motor and spatial learning deficits using the Morris water maze (MWM).
Main Results:
- MBL was detected on injured endothelial cells in WT mice after moderate CCI.
- Terminal complement activation (C3d deposition) occurred in both MBL KO and WT mice, indicating MBL is dispensable for this process after CCI.
- MBL KO mice exhibited significantly increased CA3 cell degeneration and impaired performance in cued platform MWM trials after mild CCI, suggesting a transient nonspatial learning deficit.
- Neutrophil infiltration, edema, and blood-brain barrier permeability were similar between MBL KO and WT mice after moderate CCI.
Conclusions:
- MBL deficiency exacerbates neuronal damage and impairs cognitive function after mild TBI through C3-independent mechanisms.
- These findings suggest that MBL may play a protective role in TBI, and MBL deficiency could increase susceptibility to poor outcomes after traumatic brain injury.
