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The Journal of Neuroscience, January 19, 2005, 25(3):637-647; doi:10.1523/JNEUROSCI.3960-04.2005

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

Mark A. Oatway,^1,2 Yuhua Chen,¹ Jamie C. Bruce,¹ Gregory A. Dekaban,^1,2 and Lynne C. Weaver^1,2

¹BioTherapeutics Research Group, Robarts Research Institute, and ²The Graduate Program in Neuroscience, The University of Western Ontario, London, Ontario, N6A 5K8, Canada

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.

Key words: serotonin; spinal; pain; movement; dorsal horn; intermediolateral; motoneuron; inflammation; integrin; myelin; injury

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Received Sep 23, 2004; revised November 29, 2004; accepted November 29, 2004.

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				F. Qiao, C. Atkinson, H. Song, R. Pannu, I. Singh, and S. Tomlinson Complement Plays an Important Role in Spinal Cord Injury and Represents a Therapeutic Target for Improving Recovery following Trauma Am. J. Pathol., September 1, 2006; 169(3): 1039 - 1047. [Abstract] [Full Text] [PDF]

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