Anti-CD11d Integrin Antibody Treatment Restores Normal Serotonergic Projections to the Dorsal, Intermediate, and Ventral Horns of the Injured Spinal Cord

Spinal serotonergic pathways provide inhibitory and excitatory modulation of sensory, autonomic, and motor processing. After spinal cord injury (SCI), the acute inflammatory response is one process that damages descending pathways. Increases in serotonergic fiber density in spinal segments rostral a...

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Bibliographic Details
Published in:The Journal of neuroscience 2005-01, Vol.25 (3), p.637-647
Main Authors: Oatway, Mark A, Chen, Yuhua, Bruce, Jamie C, Dekaban, Gregory A, Weaver, Lynne C
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - therapeutic use
Axonal Transport
Axons - pathology
CD11 Antigens - immunology
Hyperalgesia - physiopathology
Immunohistochemistry
Male
Movement - physiology
Myelin Sheath - pathology
Nerve Fibers - pathology
Neural Pathways - pathology
Neurobiology of Disease
Raphe Nuclei - pathology
Rats
Rats, Wistar
Serotonin - physiology
Spinal Cord - pathology
Spinal Cord - physiopathology
Spinal Cord Injuries - pathology
Spinal Cord Injuries - physiopathology
Spinal Cord Injuries - therapy
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Summary:Spinal serotonergic pathways provide inhibitory and excitatory modulation of sensory, autonomic, and motor processing. After spinal cord injury (SCI), the acute inflammatory response is one process that damages descending pathways. Increases in serotonergic fiber density in spinal segments rostral and decreases caudal to the lesion have been observed previously and may contribute to neuropathic pain and motor dysfunction associated with SCI. We investigated the effect of an acute anti-inflammatory treatment on the density of serotonergic fibers rostral and caudal to a thoracic SCI lesion. This treatment, a monoclonal antibody to the CD11d subunit of the leukocyte CD11d/CD18 integrin, limits the trafficking of neutrophils and macrophages into the SCI site. In the dorsal horn, after treatment, the typically increased serotonin immunoreactivity rostral to injury was reduced, whereas that caudal to the lesion increased toward normal. Coincidently, mechanical allodynia in the dorsal trunk and hindpaws was significantly reduced. Increased serotonergic fiber density below the lesion also occurred in the intermediolateral cell column and ventral horn of treated rats, relative to controls. Improved locomotor recovery paralleled this increased serotonin. The treatment increased compact myelin in and near the lesion epicenter and increased serotonergic fiber bundles coursing around part of the lesion but had no consistent effect on the number of raphe-spinal neurons retrogradely labeled by tracer injection below the injury. In conclusion, this anti-CD11d integrin antibody treatment is neuroprotective after SCI, corresponding with improved patterns of intraspinal serotonergic innervation. The improvement in serotonergic fiber projections paralleled reduced mechanical allodynia and enhanced locomotor recovery.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.3960-04.2005