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Presence of Trans-synaptic Neurons Derived From Olfactory Mucosa Transplanted After Spinal Cord Injury

Moriwaki, Takashi MD; Iwatsuki, Koichi MD, PhD; Mochizuki-Oda, Noriko PhD; Ohnishi, Yu-ichiro MD, PhD; Ishihara, Masahiro MD, PhD; Umegaki, Masao MD, PhD; Ninomiya, Koshi MD; Yoshimine, Toshiki MD, PhD

doi: 10.1097/BRS.0000000000000386
Basic Science

Study Design. Using biotinylated dextran amine (BDA) and wheat germ agglutinin (WGA) tracers, we measured the effectiveness of olfactory mucosa (OM) transplantation as a scaffold in a rat model of chronic spinal cord injury (SCI).

Objective. We examined whether OM transplantation for chronic SCI in rats results in reconstruction of neuronal pathways by both regeneration of the remaining axons and supply of OM-derived trans-synaptic neurons.

Summary of Background Data. OM is one of the ideal scaffolds for axonal regeneration after chronic SCI.

Methods. Rats received a mild contusion at vertebral level T6–T7. Two weeks after SCI, enhanced green fluorescent protein rat-derived OM, respiratory mucosa, and phosphate-buffered saline were transplanted into each group of SCI rats. Ten weeks after SCI, BDA was injected into the right sensorimotor cortex. Eleven weeks after SCI, WGA was injected into the L1–L2 posterior column to label the corticospinal tract retrogradely and trans-synaptically. Twelve weeks after SCI, rats were killed and their spinal cords were divided into cervical (area a), thoracic-injured (area b), and lower thoracic portions (area c). Immunohistochemically, sections of area (b) were evaluated by counting cells positive for enhanced green fluorescent protein, 4′,6-diamidino-2-phenylindole, WGA, and BDA (OM and respiratory mucosa groups). Axonal regenerations were estimated by counting WGA- and BDA-positive dots in transverse sections of area (a) and area (c).

Results. Compared with respiratory mucosa and phosphate-buffered saline transplantation, OM transplantation increased the number of WGA-positive dots in area (a), and the number of BDA-positive dots in area (c) was more after OM transplantation than after phosphate-buffered saline transplantation. Furthermore, the number of quadruple-positive cells in area (b) was much higher after OM transplantation.

Conclusion. Our results provide both indirect and direct evidence for the presence of trans-synaptic neurons. OM transplantation in rats with chronic SCI resulted in reconstruction of neural pathways by both providing trans-synaptic neurons and supporting regeneration of remaining axons. The olfactory mucosa is thought to be an efficacious scaffold to produce the relay neuron in chronic spinal cord injury.

Level of Evidence: N/A

We examined whether olfactory mucosa (OM) transplantation for rats with chronic spinal cord injury results in reconstruction of neuronal pathways by both supporting regeneration of remaining axons and providing OM-derived trans-synaptic neurons, which we call “relay-neurons.” Biotinylated dextran amine and wheat germ agglutinin were each injected into the head and lumbar regions to confirm the presence of relay-neurons.

From the Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Address correspondence and reprint requests to Koichi Iwatsuki, MD, PhD, Department of Neurosurgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; E-mail:

Acknowledgment date: November 18, 2013. Revision date: April 7, 2014. Acceptance date: April 11, 2014.

The manuscript submitted does not contain information about medical device(s)/drug(s).

JSPS KAKENHI (23592124) grant funds were received to support this work.

No relevant financial activities outside the submitted work.

© 2014 by Lippincott Williams & Wilkins