Functional repair of the corticospinal tract by delayed transplantation of olfactory ensheathing cells in adult rats

Keyvan-Fouladi, Naghmeh (2004). Functional repair of the corticospinal tract by delayed transplantation of olfactory ensheathing cells in adult rats. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000f9c2

Abstract

Adult rats were trained to use their forepaws to retrieve a piece of food through a slit in the front of the cage. The dorsal corticospinal tract was then partially or totally destroyed on one side by a small focal stereotaxic radio-frequency lesion at the level of the first or second cervical segment. Complete destruction of one side of the corticospinal tract completely abolished the use of the ipsilateral forepaw for retrieval for at least 6 months after the operation. The group of rats with the smaller lesions (destroying up to 60% of the tract) the ipsilateral forepaw was used from the first time tested, but at a reduced level, which increased progressively and reached close to normal levels by 8 weeks. The rats with the larger lesions (destroying 60% or more of the tract) did not start retrieval until the second post-operative week, and were still severely impaired at 8 weeks. The corticospinal tract is capable of transferring functions to even very small numbers of surviving fibres (1% axons), which presumably did not carry this function before the lesion. It was indicated that the total number of retrievals by the ipsilateral forepaw showed a highly significant correlation (r=0.95) with the percentage of surviving axons.
The effect of directed forepaw retrieval recovery due to transplantation of olfactory ensheathing cells were examined. In lesioned rats, which had shown no retrieval for 8 weeks after operation, a suspension of olfactory ensheathing cells was stereotaxically injected into the lesion site. From between 1 to 3 weeks after transplantation, the rats started to use the forepaw of the transplanted side, initially, at a lower rate compared with the normal side, but progressively increasing vdth time. The transplanted rats showed 40% directed forepaw retrieval recovery. Anterograde tracing (Biotin dextran) showed regenerating corticospinal axons crossing the lesion area, travelling caudally in the distal part of the corticospinal tract, and forming terminal arborisations in the spinal grey matter.
A control group of rats with injection of olfactory ensheathing cell conditioned- medium and misplaced olfactory ensheathing cell transplants showed no functional recovery during the 8 weeks of training. Experimental results suggest that the transplanted cells must be placed in direct contact with the tract to form a bridge across the lesion.
These results indicate that the regenerated corticospinal tract axons induced by delayed transplantation of olfactory ensheathing cells provides a quantitatively limited (approximately around-1% regenerating fibres) but rapidly conducting new pathway across the lesioned site.

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