SUPERIOR CERVICAL-GANGLION REGENERATING AXONS THROUGH PERIPHERAL-NERVE GRAFTS AND REVERSAL OF BEHAVIORAL DEFICITS IN HEMIPARKINSONIAN RATS

The superior cervical ganglion (SCG) has been grafted to the brain of adult rats in an attempt to reverse the parkinsonian syndrome that fol lows destruction of central dopamine systems. However, the main limita tion to this approach is the massive cell death that occurs in the gra fted SCG after direct transplantation into the brain. In adult rats, 6 -hydroxydopamine (6-OHDA) was stereotactically injected into the right substantia nigra (SN). One month later, dopamine denervation was asse ssed using the apomorphine-induced rotational test. In rats with a pos itive test, an autologous peripheral nerve (PN) graft was tunneled fro m the right cervical region to the ipsilateral parietal cortex. One en d of the PN graft was sutured to the transected postganglionic branch of the SCG and the other end was inserted into a surgically created co rtical cavity. The apomorphine test was repeated at 3 days and again a t 1, 3, and 5 months after surgery. The brain, SCG,, and PN graft were studied under light and electron microscopy and with the tyrosine hyd roxylase immunohistochemical and horseradish peroxidase tracing method s. Three days after grafting, there were no significant differences on the apomorphine test as compared to the preoperative test. Conversely , 1, 3, and 5 months after grafting, the number of rotations was reduc ed by 69% (+/- 20.2), 66.6% (+/- 17.1), and 72.5% (+/- 11.3), respecti vely. Control rats that received a free PN graft to the brain and unde rwent section of the postganglionic branch of the SCG did not show sig nificant changes on the apomorphine test after surgery. Histological e xamination revealed that the PN graft was mostly reinnervated by amyel inic axons of small caliber. Approximately 40% of the SCG neuronal pop ulation that normally projects to the postganglionic branch survived a xotomy and regenerated the transected axons into the PN graft. Axons a rising from the SCG elongated the whole length of the graft, crossed t he graft-brain interface and extended into brain regions adjacent to t he denervated striatum up to 2037 mu m from the graft insertion site. This work shows that the ingrowth of catecholamine-regenerating axons from the SCG to dopamine-depleted brain parenchyma significantly reduc es behavioral abnormalities in hemiparkinsonian rats. This effect cann ot be ascribed either to the brain cavitation or to the PN tissue plac ement in the brain.