Intracerebral xenografts of dopamine neurons: the role of immunosuppression and the blood-brain barrier

Experimental Brain Research
P BrundinA Björklund

Abstract

Fetal mesencephalic mouse tissue, rich in dopamine neurons, was xenografted as a dissociated cell suspension into the striatum of rats with unilateral 6-hydroxydopamine induced lesions of the mesostriatal pathway. The rats were either assigned to a 10-day, 21-day or 42-day Cyclosporin A (CyA) immunosuppression scheme, or given no immunosuppression. The functional effects of the grafts were followed over 6 months by monitoring changes in the recipient rats' amphetamine-induced turning behaviour. Without immunosuppression no grafts were functional at the end of the experiment. In the 10-, 21- and 42-day CyA treatment groups there was a significant reduction of rotational asymmetry at some timepoint following grafting in 26 of the 33 rats. However, by 6 months only 8 grafts remained functional suggesting that in several rats an immunological rejection took place following the termination of immunosuppression. This was supported by catecholamine histofluorescence analysis which revealed evidence of surviving grafts only in the few rats which had shown sustained functional graft effects at 6 months after grafting. In animals in which the grafts had undergone rejection, there was scar-like tissue in the striatum which appeared more e...Continue Reading

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