Neurons derived from transplanted neural stem cells restore disrupted neuronal circuitry in a mouse model of spinal cord injury

Masahiko Abematsu, Keita Tsujimura, Mariko Yamano, Michiko Saito, Kenji Kohno, Jun Kohyama, Masakazu Namihira, Setsuro Komiya, Kinichi Nakashima

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

The body's capacity to restore damaged neural networks in the injured CNS is severely limited. Although various treatment regimens can partially alleviate spinal cord injury (SCI), the mechanisms responsible for symptomatic improvement remain elusive. Here, using a mouse model of SCI, we have shown that transplantation of neural stem cells (NSCs) together with administration of valproic acid (VPA), a known antiepileptic and histone deacetylase inhibitor, dramatically enhanced the restoration of hind limb function. VPA treatment promoted the differentiation of transplanted NSCs into neurons rather than glial cells. Transsynaptic anterograde corticospinal tract tracing revealed that transplant-derived neurons reconstructed broken neuronal circuits, and electron microscopic analysis revealed that the transplant-derived neurons both received and sent synaptic connections to endogenous neurons. Ablation of the transplanted cells abolished the recovery of hind limb motor function, confirming that NSC transplantation directly contributed to restored motor function. These findings raise the possibility that epigenetic status in transplanted NSCs can be manipulated to provide effective treatment for SCI.

Original languageEnglish
Pages (from-to)3255-3266
Number of pages12
JournalJournal of Clinical Investigation
Volume120
Issue number9
DOIs
Publication statusPublished - 2010 Sep 1
Externally publishedYes

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Neural Stem Cells
Spinal Cord Injuries
Neurons
Valproic Acid
Extremities
Transplants
Pyramidal Tracts
Histone Deacetylase Inhibitors
Stem Cell Transplantation
Epigenomics
Neuroglia
Anticonvulsants
Therapeutics
Transplantation
Electrons

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Neurons derived from transplanted neural stem cells restore disrupted neuronal circuitry in a mouse model of spinal cord injury. / Abematsu, Masahiko; Tsujimura, Keita; Yamano, Mariko; Saito, Michiko; Kohno, Kenji; Kohyama, Jun; Namihira, Masakazu; Komiya, Setsuro; Nakashima, Kinichi.

In: Journal of Clinical Investigation, Vol. 120, No. 9, 01.09.2010, p. 3255-3266.

Research output: Contribution to journalArticle

Abematsu, M, Tsujimura, K, Yamano, M, Saito, M, Kohno, K, Kohyama, J, Namihira, M, Komiya, S & Nakashima, K 2010, 'Neurons derived from transplanted neural stem cells restore disrupted neuronal circuitry in a mouse model of spinal cord injury', Journal of Clinical Investigation, vol. 120, no. 9, pp. 3255-3266. https://doi.org/10.1172/JCI42957
Abematsu, Masahiko ; Tsujimura, Keita ; Yamano, Mariko ; Saito, Michiko ; Kohno, Kenji ; Kohyama, Jun ; Namihira, Masakazu ; Komiya, Setsuro ; Nakashima, Kinichi. / Neurons derived from transplanted neural stem cells restore disrupted neuronal circuitry in a mouse model of spinal cord injury. In: Journal of Clinical Investigation. 2010 ; Vol. 120, No. 9. pp. 3255-3266.
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