Journal
CEREBRAL CORTEX
Volume 29, Issue 2, Pages 561-572Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhx338
Keywords
corticospinal tract; manual dexterity; primates; repulsive guidance molecule-a; spinal cord injury
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Funding
- Core Research for Evolutional Science and Technology (CREST) program from the Japan Science and Technology Agency
- Strategic Research Program for Brain Sciences from the Japan Agency for Medical Research and Development
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [15H01434]
- Grants-in-Aid for Scientific Research [16H01611, 15H01434, 16H02454, 17K19454, 17H05567] Funding Source: KAKEN
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Axons in the mature mammalian central nervous system have only a limited capacity to grow/regenerate after injury, and spontaneous recovery of motor functions is therefore not greatly expected in spinal cord injury (SCI). To promote functional recovery after SCI, it is critical that corticospinal tract (CST) fibers reconnect properly with target spinal neurons through enhanced axonal growth/regeneration. Here, we applied antibody treatment against repulsive guidance molecule-a (RGMa) to a monkey model of SCI. We found that inhibition of upregulated RGMa around the lesioned site in the cervical cord resulted in recovery from impaired manual dexterity by accentuated penetration of CST fibers into laminae VII and IX, where spinal interneurons and motoneurons are located, respectively. Furthermore, pharmacological inactivation following intracortical microstimulation revealed that the contralesional, but not the ipsilesional, primary motor cortex was crucially involved in functional recovery at a late stage in our SCI model. The present data indicate that treatment with the neutralizing antibody against RGMa after SCI is a potential target for achieving restored manual dexterity in primates.
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