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The Journal of Neuroscience, December 26, 2007, 27(52):14260-14264; doi:10.1523/JNEUROSCI.4571-07.2007

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Brief Communications
Human Neuroma Contains Increased Levels of Semaphorin 3A, Which Surrounds Nerve Fibers and Reduces Neurite Extension In Vitro

Martijn R. Tannemaat,1,2 Joanna Korecka,1 Erich M. E. Ehlert,1 Matthew R. J. Mason,1 Sjoerd G. van Duinen,3 Gerard J. Boer,1 Martijn J. A. Malessy,2 and Joost Verhaagen1

1Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, An Institute of the Royal Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands, and 2Department of Neurosurgery and 3Department of Pathology and Neurology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands

Correspondence should be addressed to Dr. Joost Verhaagen, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam ZO, The Netherlands. Email: j.verhaagen{at}nin.knaw.nl

Neuroma formation after peripheral nerve injury is detrimental to functional recovery and is therefore a significant clinical problem. The molecular basis for this phenomenon is not fully understood. Here, we show that the expression of the chemorepulsive protein semaphorin 3A (sema3A), but not semaphorin 3F, is increased in human neuroma tissue that has formed in severe obstetric brachial plexus lesions. Sema3A is produced by fibroblasts in the epineurial space and appears to be secreted into the extracellular matrix. It surrounds fascicles, minifascicles, or single axons, suggesting a role in fasciculation and inhibition of neurite outgrowth. Lentiviral vector-mediated knock-down of Neuropilin 1, the receptor for sema3A, leads to increased neurite outgrowth of F11 cells cultured on neuroma tissue, but not of F11 cells cultured on normal nerve tissue. These findings demonstrate the putative inhibitory role of sema3A in human neuroma tissue. Our observations are the first demonstration of the expression of sema3A in human neural scar tissue and support a role for this protein in the inhibition of axonal regeneration in injured human peripheral nerves. These findings contribute to the understanding of the outgrowth inhibitory properties of neuroma tissue.

Key words: semaphorin 3A; peripheral nerve; regeneration; inhibition; fasciculation; neuroma; brachial plexus

Received April 26, 2007; accepted Nov. 2, 2007.

Correspondence should be addressed to Dr. Joost Verhaagen, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam ZO, The Netherlands. Email: j.verhaagen{at}nin.knaw.nl






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