Reinnervation of the denervated adult spinal cord of rats by intraspinal transplants of embryonic brain stem neurons

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Abstract
Summary Previous studies have revealed a remarkable capacity of intracerebral grafts of embryonic brain tissue to establish extensive axonal connections with denervated areas in the brains of adult rats. In the present study we have explored the possibilities of using grafts in the spinal cord to substitute for the loss of noradrenergic brain-stem inputs to the severed spinal cord. Intraspinal grafts of embryonic pontine noradrenergic neurons were made into the lower thoracic region of adult rats. Three different surgical techniques were tested: (i) grafting to a small central cavity in the spinal-cord grey matter; (ii) grafting to a small subpial cavity involving removal of the dorsolateral third of the spinal-cord matter; (iii) grafting to the gap between the rostral and caudal stumps of the spinal cord after a nearly complete subpial transection. The results indicate that direct contact with the vessel-rich pia is essential for good survival of the grafts. Provided that the pia was left intact, the scarring around the grafts was minimal and the grafts fused well with both the grey and white matter of the cord. In the subpially transected cord, a brain-stem graft taken from a young embryonic donor fused well with both the rostral and the caudal stumps of the severed cord and thus restored tissue continuity across the gap. Large numbers of catecholamine (CA)-containing and non-monoaminergic cells were present in the transplants after 3–6 months. CA fluorescence histochemistry in combination with injections of fluorescent retrograde tracers revealed that both noradrenergic and non-monoaminergic neurons in the grafts had grown to reinnervate large segments of the host spinal cord. In those cases where the transplant had fused well with the cord, abundant CA-fluorescent axons could be traced across the graft-cord junction. They course along the grey and white matter of the host cord to reestablish a new CA terminal plexus in the grey matter as far as 12 mm from the graft.