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Depletion of Ly6G/Gr-1 leukocytes after spinal cord injury in mice alters wound healing and worsens neurological outcome.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2009 Jan 21; Vol. 29 (3), pp. 753-64. - Publication Year :
- 2009
-
Abstract
- Spinal cord injury (SCI) induces a robust inflammatory response and the extravasation of leukocytes into the injured tissue. To further knowledge of the functions of neuroinflammation in SCI in mice, we depleted the early arriving neutrophils using an anti-Ly6G/Gr-1 antibody. Complete blood counts revealed that neutrophils increased approximately 3-fold over uninjured controls and peaked at 6-12 h after injury, and that anti-Ly6G/Gr-1 treatment reduced circulating neutrophils by >90% at these time points. Intravital and spinning disk confocal microscopy of the exposed posterior vein and postcapillary venules showed a significant reduction in rolling and adhering neutrophils in vivo after anti-Ly6G/Gr-1 treatment; this was accompanied by a parallel reduction in neutrophil numbers within the injured spinal cord at 24 and 48 h as determined by flow cytometry. The evolution of astrocyte reactivity, a wound healing response, was reduced in anti-Ly6G/Gr-1-treated mice, which also had less spared white matter and axonal preservation compared with isotype controls. These histological outcomes may be caused by alterations of growth factors and chemokines important in promoting wound healing. Importantly, anti-Ly6G/Gr-1 treatment worsened behavioral outcome as determined using the Basso Mouse Scale and subscores. Although the spectrum of cells affected by anti-Ly6G/Gr-1 antibody treatment cannot be fully ascertained at this point, the correspondence of neutrophil depletion and worsened recovery suggests that neutrophils promote recovery after SCI through wound healing and protective events that limit lesion propagation.
- Subjects :
- Analysis of Variance
Animals
Antibodies pharmacology
Antigens, Ly immunology
Behavior, Animal drug effects
Calcium-Binding Proteins metabolism
Cytokines metabolism
Disease Models, Animal
Flow Cytometry methods
Glial Fibrillary Acidic Protein metabolism
Green Fluorescent Proteins genetics
Intercellular Signaling Peptides and Proteins metabolism
Leukocytes drug effects
Mice
Mice, Transgenic
Microfilament Proteins
Myeloid Cells drug effects
Myeloid Cells physiology
Neurofilament Proteins metabolism
Neutrophils drug effects
Severity of Illness Index
Time Factors
Wound Healing drug effects
Antigens, Ly metabolism
Leukocytes metabolism
Spinal Cord Injuries blood
Spinal Cord Injuries physiopathology
Wound Healing physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 29
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 19158301
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.4918-08.2009