Human adult olfactory neural progenitors promote axotomized rubrospinal tract axonal reinnervation and locomotor recovery

Ming Xiao; Kathleen M. Klueber; JianPing Zhou; Zhanfang Guo; Chengliang Lu; Heming Wang; Fred J. Roisen

Neurobiology of Disease (May 2007)

Human adult olfactory neural progenitors promote axotomized rubrospinal tract axonal reinnervation and locomotor recovery

Ming Xiao,
Kathleen M. Klueber,
JianPing Zhou,
Zhanfang Guo,
Chengliang Lu,
Heming Wang,
Fred J. Roisen

Affiliations

Ming Xiao: Department of Human Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 210029 China; Corresponding authors. M. Xiao is to be contacted at fax: +86 11 86 25 2912. F.J. Roisen, fax: +1 502 852 6228.
Kathleen M. Klueber: Anatomical Sciences and Neurobiology, University of Louisville, KY 40202, USA
JianPing Zhou: Department of Human Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 210029 China; Anatomical Sciences and Neurobiology, University of Louisville, KY 40202, USA
Zhanfang Guo: Department of Human Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 210029 China
Chengliang Lu: Department of Human Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 210029 China
Heming Wang: Department of Human Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 210029 China
Fred J. Roisen: Anatomical Sciences and Neurobiology, University of Louisville, KY 40202, USA; Corresponding authors. M. Xiao is to be contacted at fax: +86 11 86 25 2912. F.J. Roisen, fax: +1 502 852 6228.

Journal volume & issue: Vol. 26, no. 2
pp. 363 – 374

Abstract

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We investigated the effects of engrafted human adult olfactory neuroepithelial neurosphere forming cells (NSFCs) on regeneration and reinnervation of rubrospinal tract (RST) axons and locomotor recovery following partial cervical hemisection that completely ablated the RST. Weekly behavioral testing showed greater functional recovery of forelimb use during the 12 weeks after NSFCs engraftment than in the control rats. Anterograde tracing with biotinylated dextran amine (BDA) confirmed the presence of RST axons within the white matter 4–8 segments caudal to the grafts. Both immunofluorescence and immunoelectron microscopy revealed the BDA-labeled RST axonal terminals reestablished synaptic connections with motoneurons in the ventral horn of the distal cervical spinal cord. Further study of forelimb functional recovery in NSFCs-engrafted subgroups considered the effects of a second dorsolateral funiculotomy, irreversibly destroying the recovery, and the injection of muscimol, blocking RST neuronal activity reversibly. These results highlight the unique potential of human olfactory neuroepithelial-derived progenitors as an autologous cell source for spinal cord repair.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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