| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
The severed central processes of adult dorsal root ganglion (DRG) neurons regenerate into embryonic spinal cord transplants and form contacts with transplant neurons that are synaptically driven in response to electrical stimulation of regenerated DRG axons. It is unknown whether embryonic spinal cord transplants also mediate adult dorsal root axonal regeneration into host spinal cord, and whether it is due to properties shared by tissue from different regions of the CNS.Adult female sprague-Dawley rats received intraspinal transplants of E14 spinal cord, E16 hippocampus, or E18 occipital cortex into left dorsal quadrant cavities created at the lumbar enlargement. The cut host L4 or L5 dorsal root stump was sandwiched between the transplant and host spinal cord. Three to 12 months after graft sagittal cryostat sections were processed for calcitonin gene-related peptide (CGRP) immunohistochemistry and the extent of dorsal root axonal regeneration into host spinal cord was analyzed quantitatively. CGRP-immunoreactive axons regenerated into host spinal cord in all transplanted animals and some extended into host motoneuron pool. The area fraction occupied by regenerated axons and the area of axon distribution in transplanted rats of spinal cord were significantly larger than in those of hippocampus, occipital cortex, or control rats without transplants. CGRP-labeled axons formed synaptic terminals within host spinal cord with fetal spinal cord grafts 1 year after transplantation. Embryonic CNS transplants, especially spinal cord grafts, mediate permanent synapse formation by adult DRG axons within host spinal cord. Furthermore, neurotrophin-3 (NT-3)-contained-fibrin glue ball grafted intraspinally, also enhance the regeneration of DRG axons into adult spinal cord. These results indicated that the transplants may release neurotrophic agents like NT-3 to provide a milieu that promotes reconstruction of interrupted spinal reflex arcs.
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